A 55‐year‐old man was admitted to the hospital for amputation of multiple toes secondarily infected in the setting of severe tophaceous gout. He had been wheelchair bound for several years because of severe gouty arthritis. His medical history was remarkable for previous arthroscopies of his hands, knees, and Achilles tendons to remove uric acid deposits, in addition to multiple episodes of nephrolithiasis from uric acid stones. His family history was remarkable for severe, debilitating gout in multiple first‐degree relatives. On further examination he was noted to have severe tophaceous gouty involvement of numerous joints (arrows in Figs. 1 and 2). His uric acid level was 11.6 mg/dL despite receiving 900 mg of allopurinol daily. Because his creatinine was 1.7 mg/dL on admission, his dose of allopurinol was reduced. Renal ultrasound revealed multiple bilateral renal stones (arrows in Fig. 3).

Figure 1

Figure 2

Figure 3

He underwent surgery, and was subsequently transferred to a skilled nursing facility for wound care and physical therapy, where he recuperated uneventfully.

A 55‐year‐old man was admitted to the hospital for amputation of multiple toes secondarily infected in the setting of severe tophaceous gout. He had been wheelchair bound for several years because of severe gouty arthritis. His medical history was remarkable for previous arthroscopies of his hands, knees, and Achilles tendons to remove uric acid deposits, in addition to multiple episodes of nephrolithiasis from uric acid stones. His family history was remarkable for severe, debilitating gout in multiple first‐degree relatives. On further examination he was noted to have severe tophaceous gouty involvement of numerous joints (arrows in Figs. 1 and 2). His uric acid level was 11.6 mg/dL despite receiving 900 mg of allopurinol daily. Because his creatinine was 1.7 mg/dL on admission, his dose of allopurinol was reduced. Renal ultrasound revealed multiple bilateral renal stones (arrows in Fig. 3).

Figure 1

Figure 2

Figure 3

He underwent surgery, and was subsequently transferred to a skilled nursing facility for wound care and physical therapy, where he recuperated uneventfully.

A 55‐year‐old man was admitted to the hospital for amputation of multiple toes secondarily infected in the setting of severe tophaceous gout. He had been wheelchair bound for several years because of severe gouty arthritis. His medical history was remarkable for previous arthroscopies of his hands, knees, and Achilles tendons to remove uric acid deposits, in addition to multiple episodes of nephrolithiasis from uric acid stones. His family history was remarkable for severe, debilitating gout in multiple first‐degree relatives. On further examination he was noted to have severe tophaceous gouty involvement of numerous joints (arrows in Figs. 1 and 2). His uric acid level was 11.6 mg/dL despite receiving 900 mg of allopurinol daily. Because his creatinine was 1.7 mg/dL on admission, his dose of allopurinol was reduced. Renal ultrasound revealed multiple bilateral renal stones (arrows in Fig. 3).

Figure 1

Figure 2

Figure 3

He underwent surgery, and was subsequently transferred to a skilled nursing facility for wound care and physical therapy, where he recuperated uneventfully.

A 62‐year‐old man with psoriasis for more than 30 years presented to the emergency department with a scaly, pruritic rash involving his face, trunk, and extremities that he had had for the past 10 days. The rash was spreading and not responding to application of clobetasol ointment, which had helped his psoriasis in the past. He also reported mild pharyngitis, headache, and myalgias.

A patient with a chronic skin condition presenting with a new rash means the clinician must consider whether it is an alternative manifestation of the chronic disorder or a new illness. Psoriasis takes many forms including guttate psoriasis, which presents with small, droplike plaques and frequently follows respiratory infections (particularly those caused by Streptococcus). Well‐controlled psoriasis rarely transforms after 3 decades, so I would consider other conditions. The tempo of illness makes certain life‐threatening syndromes, including Stevens‐Johnson, toxic shock, and purpura fulminans, unlikely. An allergic reaction, atopic dermatitis, or medication reaction is possible. Infections, either systemic (eg, syphilis) or dermatologic (eg, scabies), should be considered. Photosensitivity could involve the sun‐exposed areas, such as the extremities and face. Seborrheic dermatitis can cause scaling lesions of the face and trunk but not the extremities. Vasculitis merits consideration, but dependent regions are typically affected more than the head. Mycosis fungoides or a paraneoplastic phenomenon could cause a diffuse rash in this age group.

The patient had diabetes mellitus, hypertension, diverticulosis, and depression. Three months earlier he had undergone surgical drainage of a perirectal abscess. His usual medications were lovastatin, paroxetine, insulin, hydrochlorothiazide, and lisinopril. Three weeks previously he had completed a 10‐day course of trimethoprim/sulfamethoxazole for an upper respiratory infection. Otherwise, he was taking no new medications. He was allergic to penicillin. He denied substance abuse, recent travel, or risk factors for human immunodeficiency virus (HIV) infection. He worked as an automobile painter, lived with his wife, and had a pet dog.

Physical examination revealed a well‐appearing man with normal vital signs. His skin had well‐defined circumscribed pink plaques, mostly 1‐2 cm in size, with thick, silvery scales in the ears and on the dorsal and ventral arms and legs, chest, back, face, and scalp. There were no pustules or other signs of infection (Figs. 1and 2). The nails exhibited distal onycholysis, oil spots, and rare pits. His posterior pharynx was mildly erythematous. The results of cardiovascular, pulmonary, and abdominal examinations were normal.

Figure 1

Figure 2

Although other scaling skin conditions such as eczema, irritant dermatitis, or malignancy remain possible, his rash is most consistent with widespread psoriasis. I would consider immunological changes that may have caused a remarkably altered and more severe expression of his chronic disease, for example, recent steroid therapy or HIV infection. The company a rash keeps helps frame the differential diagnosis. Based on the patient's well appearance, the time course, his minimal systemic symptoms, and the appearance of the rash, my leading considerations are psoriasis or an allergic dermatitis. Cutaneous T‐cell malignancy, with its indolent and sometimes protean manifestations, remains possible in a patient of his age. I would now consult a dermatologist for 3 reasons: this patient has a chronic disease that I do not manage beyond basic treatments (eg, topical steroids), he has an undiagnosed illness with substantial dermatologic manifestations, and he may need a skin biopsy for definitive diagnosis.

The dermatology team diagnosed a guttate psoriasis flare, possibly associated with streptococcal pharyngitis. The differential diagnosis included secondary syphilis, although the team believed this was less likely. The dermatology team recommended obtaining a throat culture, streptozyme assay, and rapid plasma reagin and prescribed oral erythromycin and topical steroid ointment under a sauna suit.

I would follow his response to the prescribed steroid treatments. If the patient's course deviates from the dermatologists' expectations, I would request a skin biopsy and undertake further evaluations in search of an underlying systemic disease.

The patient followed up in the dermatology clinic 3 weeks later. His rash had worsened, and he had developed patchy alopecia and progressive edema of the face, ears, and eyes. He denied mouth or tongue swelling, difficulty breathing, or hives. The streptozyme assay was positive, but the other laboratory test results were negative.

The dermatology team diagnosed a severely inflammatory psoriasis flare and prescribed an oral retinoid, acitretin, and referred him for ultraviolet light therapy. He was unable to travel for phototherapy, and acitretin was discontinued after 1 week because of elevated serum transaminase levels. The dermatologists then prescribed oral cyclosporine.

The progression of disease despite standard treatment suggests a nonpsoriatic condition. Although medications could cause the abnormal liver tests, so could another underlying illness that involves the liver. An infiltrative disorder of the skin with hair follicle destruction and local lymphedema could explain both alopecia and facial edema.

I am unable account for his clinical features with a single disease, so the differential remains broad, including severe psoriasis, an infiltrating cutaneous malignancy, or a toxic exposure. Arsenic poisoning causes hyperkeratotic skin lesions, although he lacks the associated gastrointestinal and neurological symptoms. I would not have added the potentially toxic cyclosporine.

When he returned to dermatology clinic 1 week later, his rash and facial swelling had worsened. He also reported muscle and joint aches, fatigue, lightheadedness, anorexia, nausea, abdominal pain, diarrhea, and dyspnea on exertion. He denied fever, chills, and night sweats.

He appeared ill and used a cane to arise and walk. His vital signs and oxygen saturation were normal. He had marked swelling of his face, diffuse erythema and swelling on the chest, and widespread scaly, erythematous plaques (Fig. 3). The proximal nail folds of his fingers were erythematous, with ragged cuticles. His abdomen was mildly distended, but the rest of the physical examination was normal.

Figure 3

He has become too systemically ill to attribute his condition to psoriasis. The nail findings suggest dermatomyositis, which could explain many of his findings. The diffuse erythema and his difficulty walking are consistent with its skin and muscle involvement. Dyspnea could be explained by dermatomyositis‐associated interstitial lung disease. A dermatomyositis‐associated hematological or solid malignancy could account for his multisystem ailments and functional decline. A point against dermatomyositis is the relatively explosive onset of his disease. He should be carefully examined for any motor weakness. With his progressive erythroderma, I am also concerned about an advancing cutaneous T‐cell lymphoma (with leukemic transformation).

Blood tests revealed the following values: white‐blood‐cell count, 8700/L; hematocrit, 46%; platelet count, 172,000/L; blood urea nitrogen, 26 mg/dL; creatinine, 1.0 mg/dL; glucose, 199 mg/dL; albumin, 3.1 g/dL; alkaline phosphatase, 172 U/L (normal range 45‐129); alanine aminotransferase, 75 U/L (normal range 0‐39 U/L); aspartate aminotransferase, 263 U/L (normal range 0‐37 U/L); total bilirubin, 1.1 mg/dL; prothrombin time, 16 seconds (normal range 11.7‐14.3 seconds), and serum creatinine, kinase, 4253 U/L (normal range 0‐194 U/L). HIV serology was negative. Urinalysis revealed trace protein. The results of chest radiographs and an electrocardiogram were normal.

The liver function tests results are consistent with medication effects or liver involvement in a systemic disease. The creatinine kinase elevation is consistent with a myopathy such as dermatomyositis. A skin biopsy would still be useful. Depending on those results, he may need a muscle biopsy, urine heavy metal testing, and computed tomography body imaging. Considering his transaminase and creatinine kinase elevations, I would discontinue lovastatin.

The patient was hospitalized. Further questioning revealed that he had typical Raynaud's phenomenon and odynophagia. A detailed neurological examination showed weakness (3/5) of the triceps and iliopsoas muscles and difficulty rising from a chair without using his arms. Dermatoscopic examination of the proximal nail folds showed dilated capillary loops and foci of hemorrhage.

Blood tests showed a lactate dehydrogenase level of 456 U/L (normal range 0‐249 U/L) and an aldolase of 38 U/L (normal range 1.2‐7.6 U/L). Tests for antinuclear antibodies, anti‐Jo antibody, and antimyeloperoxidase antibodies were negative. Two skin biopsies were interpreted by general pathology as consistent with partially treated psoriasis, whereas another showed nonspecific changes with minimal superficial perivascular lymphohistiocytic inflammation (Fig. 4). Lisinopril was discontinued because of its possible contribution to the facial edema.

Figure 4

Dermatomyositis is now the leading diagnosis. Characteristic features include his proximal muscle weakness, Raynaud's phenomenon, and dilated nailfold capillary loops. I am not overly dissuaded by the negative antinuclear antibodies, but because of additional atypical features (ie, extensive cutaneous edema, rapid onset, illness severity, prominent gastrointestinal symptoms), a confirmatory muscle biopsy is needed. Endoscopy of the proximal aerodigestive tract would help evaluate the odynophagia. There is little to suggest infection, malignancy, or metabolic derangement.

The inpatient medical team considered myositis related to retinoid or cyclosporine therapy. They discontinued cyclosporine and began systemic corticosteroid therapy. Within a few days, the patient's rash, muscle pain, and weakness improved, and the elevated transaminase and creatinine kinase levels decreased.

Dermatology recommended an evaluation for dermatomyositis‐associated malignancy, but the medicine team and rheumatology consultants, noting the lack of classic skin findings (heliotrope rash and Gottron's papules) and the uncharacteristically rapid onset and improvement of myositis, suggested delaying the evaluation until dermatomyositis was proven.

An immediate improvement in symptoms with steroids is nonspecific, often occurring in autoimmune, infectious, and neoplastic diseases. This juncture in the case is common in complex multisystem illnesses, where various consultants may arrive at differing conclusions. With both typical and atypical features of dermatomyositis, where should one set the therapeutic threshold, that is, the point where one ends testing, accepts a diagnosis, and initiates treatment? Several factors raise the level of certainty I would require. First, dermatomyositis is quite rare. Adding atypical features further increases the burden of proof for that illness. Second, the existence of alternative possibilities (admittedly of equal uncertainty) gives me some pause. Finally, the toxicity of the proposed treatments raises the therapeutic threshold. Acknowledging that empiric treatment may be indicated for a severely ill patient at a lower level of certainty, I would hesitate to commit a patient to long‐term steroids without being confident of the diagnosis. I would therefore require a muscle biopsy, or at least electromyography to support or exclude dermatomyositis.

The patient was discharged from the hospital on high‐dose prednisone. He underwent electromyography, which revealed inflammatory myopathic changes more apparent in the proximal than distal muscles. These findings were thought to be compatible with dermatomyositis, although the fibrillations and positive sharp waves characteristic of acute inflammation were absent, perhaps because of corticosteroid therapy.

The patient mistakenly stopped taking his prednisone. Within days, his weakness and skin rash worsened, and he developed nausea with vomiting. He returned to clinic, where his creatinine kinase level was again found to be elevated, and he was rehospitalized. Oral corticosteroid therapy was restarted with prompt improvement. On review of the original skin biopsies, a dermatopathologist observed areas of thickened dermal collagen and a superficial and deep perivascular lymphocytic infiltrate, both consistent with connective tissue disease.

These 3 additional findings (ie, electromyography results, temporally established steroid responsiveness, and the new skin biopsy interpretation) in aggregate support the diagnosis of dermatomyositis, but the nausea and vomiting are unusual. I would discuss these results with a rheumatologist and still request a confirmatory muscle biopsy. Because diagnosing dermatomyositis should prompt consideration of seeking an underlying malignancy in a patient of this age group, I would repeat a targeted history and physical examination along with age‐ and risk‐factor‐appropriate screening. If muscle biopsy results are not definitive, finding an underlying malignancy would lend support to dermatomyositis.

While hospitalized, the patient complained of continued odynophagia and was noted to have oral candidiasis. Upper endoscopy, undertaken to evaluate for esophageal candidiasis, revealed a mass at the gastroesophageal junction. Biopsy revealed gastric‐type adenocarcinoma. An abdominal computed tomography scan demonstrated 3 hypodense hepatic lesions, evidence of cirrhosis, and ascites. Cytology of paracentesis fluid revealed cells compatible with adenocarcinoma. The patient died in hospice care 2 weeks later.

At autopsy, he had metastatic gastric‐type adenocarcinoma. A muscle biopsy (Fig. 5) revealed muscle atrophy with small foci of lymphocytic infiltrates, most compatible with dermatomyositis. Another dermatopathologist reviewed the skin biopsies and noted interface dermatitis, which is typical of connective tissue diseases like dermatomyositis (Fig. 6A,B).

Figure 5

Figure 6

COMMENTARY

Dermatomyositis is an idiopathic inflammatory myopathy characterized by endomysial inflammation and muscle weakness and differentiated from other myopathies by the presence of a rash.1 Muscle disease may manifest with or precede the rash, but up to 40% of patients present with skin manifestations alone, an entity called amyopathic dermatomyositis.2 When present, the myositis generally develops over months, but the onset can be acute.1 The weakness is typically symmetrical and proximal,1 and many patients have oropharyngeal dysphagia.3

The characteristic rash is erythematous, symmetrical, and photodistributed.4 Classic cutaneous findings are the heliotrope rash (violaceous eyelid erythema), which is pathognomonic but uncommon, and the more common Gottron's papules (violaceous, slightly elevated papules and plaques on bony prominences and extensor surfaces, especially the knuckles).4 Other findings include periorbital edema, scalp dermatitis, poikiloderma (ie, hyperpigmentation, hypopigmentation, atrophy, and telangiectasia), periungual erythema, and dystrophic cuticles.2 The cutaneous manifestations of dermatomyositis may be similar to those of psoriasis, systemic lupus erythematosus, lichen planus, rosacea, polymorphous light eruption, drug eruption, atopic dermatitis, seborrheic dermatitis, or allergic contact dermatitis.4

Diagnosing dermatomyositis requires considering clinical, laboratory, electromyographical, and histological evidence, as there are no widely accepted, validated diagnostic criteria.1, 5 The diagnosis is usually suspected if there is a characteristic rash and symptoms of myositis (eg, proximal muscle weakness, myalgias, fatigue, or an inability to swallow). When the patient has an atypical rash, skin biopsy can differentiate dermatomyositis from other conditions, except lupus, which shares the key finding of interface dermatitis.2 The histological findings can be variable and subtle,6 so consultation with a dermatopathologist may be helpful.

Myositis may be confirmed by various studies. Most patients have elevated muscle enzymes (ie, creatinine kinase, aldolase, lactate dehydrogenase, or transaminases)1; for those who do not, magnetic resonance imaging can be helpful in detecting muscle involvement and locating the best site for muscle biopsy.7 Electromyography reveals nonspecific muscle membrane instability.8 Muscle biopsy shows muscle fiber necrosis, perifascicular atrophy, and perivascular and perifascicular lymphocytic infiltrates. These can be patchy, diminished by steroid use, and occasionally seen in noninflammatory muscular dystrophies.8 For a patient with typical myositis and a characteristic rash, muscle biopsy may be unnecessary.1

The clinical utility of serologic testing for diagnosing dermatomyositis is controversial.2 Myositis‐specific antibody testing is insensitive but specific; these antibodies include Jo‐1, an antisynthetase antibody that predicts incomplete response to therapy and lung involvement, and Mi‐2, which is associated with better response to therapy.2, 9, 10 The sensitivity and specificity of antinuclear antibodies are both approximately 60%.10

Patients with dermatomyositis have higher rates of cancers than age‐matched controls, and nearly 25% of patients are diagnosed with a malignancy at some point during the course of the disease.11 Malignancies are typically solid tumors that manifest within 3 years of the diagnosis,1214 although the increased risk may exist for at least 5 years.14 There is a 10‐fold higher risk of ovarian cancer in women with dermatomyositis.12, 15 Other associated malignancies include lung, gastric, colorectal, pancreatic, and breast carcinomas and non‐Hodgkin's lymphoma.14

Recommendations for screening affected patients for cancer have changed over the years, with increasing evidence of an association between dermatomyositis and malignancy and evolving improvements in diagnostic techniques.16 Many authorities recommend that all adult patients with dermatomyositis be evaluated for cancer, including a complete physical examination, basic hematological tests, age‐ and sex‐appropriate screening (eg, mammography, pap smear, and colonoscopy), and chest x‐ray.16 Some would add upper endoscopy; imaging of the chest, abdomen, and pelvis; gynecological examination; and serum CA‐125 level to better evaluate for the most common malignancies (ie, ovarian, gastric, lung, and pancreatic carcinomas and non‐Hodgkins lymphoma).12, 1720

In 19% of adults, dermatomyositis overlaps with other autoimmune disorders, usually systemic lupus erythematosus and systemic sclerosis.21 These manifest as Raynaud's phenomenon, arthritis, esophageal dysmotility, renal disease, or neuropathy.21 Other potentially serious systemic manifestations of dermatomyositis include proximal dysphagia from pharyngeal myopathy; distal dysphagia from esophageal dysmotility in systemic sclerosis overlap; pulmonary disease from autoimmune interstitial lung disease or aspiration; cardiac disease from conduction abnormalities, myocarditis, pericarditis, and valvular disease; and rhabdomyolysis.2

Treatment of dermatomyositis requires systemic immunosuppression with 1 or more agents. The prognosis of dermatomyositis is variable. Mortality at 5 years ranges from 23% to 73%. At least a third of patients are left with mild to severe disability.1 In addition to older age, predictors of poor outcome include male sex, dysphagia, longstanding symptoms before treatment, pulmonary or cardiac involvement, and presence of antisynthetase antibodies.22

Dermatomyositis is often treated in the outpatient setting, but there are many reasons for hospitalization. Complications of treatment, like infection or adverse effects of medications, could result in hospitalization. Treatment with intravenous pulse corticosteroids or IVIG may require inpatient administration if no infusion center is available. Other indications for inpatient evaluation include the consequences of various malignancies and the more severe expression of systemic complications of dermatomyositis (eg, dysphagia and pulmonary, cardiac, or renal disease).

Every parent knows the plaintive backseat whine, Are we there, yet? Clinicians may also experience this feeling when attempting to diagnose a perplexing illness, especially one that lacks a definitive diagnostic test. It was easy for this patient's doctors to assume initially that his new rash was a manifestation of his long‐standing psoriasis. Having done so, they could understandably attribute the subsequent findings to either evolution of this disease or to consequences of the prescribed treatments, rather than considering a novel diagnosis. Only when faced with new (or newly appreciated) findings suggesting myopathy did the clinicians (and our discussant) consider the diagnosis of dermatomyositis. Even then, the primary inpatient medical team and their consultants were unsure when they had sufficient evidence to be certain.

Several factors compounded the difficulty of making a diagnosis in this case: the clinicians were dealing with a rare disease; they were considering alternative diagnoses (ie, psoriasis or a toxic effect of medication); and the disease presented somewhat atypically. The clinicians initially failed to consider and then accept the correct diagnosis because the patient's rash was not classic, his biopsy was interpreted as nonspecific, and he lacked myositis at presentation. Furthermore, when the generalists sought expert assistance, they encountered a difference of opinion among the consultants. These complex situations should goad the clinician into carefully considering the therapeutic threshold, that is, the transition point from diagnostic testing to therapeutic intervention.23 With complex cases like this, it may be difficult to know when one has reached a strongly supported diagnosis, and frequently asking whether we are there yet may be appropriate.

A 62‐year‐old man with psoriasis for more than 30 years presented to the emergency department with a scaly, pruritic rash involving his face, trunk, and extremities that he had had for the past 10 days. The rash was spreading and not responding to application of clobetasol ointment, which had helped his psoriasis in the past. He also reported mild pharyngitis, headache, and myalgias.

A patient with a chronic skin condition presenting with a new rash means the clinician must consider whether it is an alternative manifestation of the chronic disorder or a new illness. Psoriasis takes many forms including guttate psoriasis, which presents with small, droplike plaques and frequently follows respiratory infections (particularly those caused by Streptococcus). Well‐controlled psoriasis rarely transforms after 3 decades, so I would consider other conditions. The tempo of illness makes certain life‐threatening syndromes, including Stevens‐Johnson, toxic shock, and purpura fulminans, unlikely. An allergic reaction, atopic dermatitis, or medication reaction is possible. Infections, either systemic (eg, syphilis) or dermatologic (eg, scabies), should be considered. Photosensitivity could involve the sun‐exposed areas, such as the extremities and face. Seborrheic dermatitis can cause scaling lesions of the face and trunk but not the extremities. Vasculitis merits consideration, but dependent regions are typically affected more than the head. Mycosis fungoides or a paraneoplastic phenomenon could cause a diffuse rash in this age group.

The patient had diabetes mellitus, hypertension, diverticulosis, and depression. Three months earlier he had undergone surgical drainage of a perirectal abscess. His usual medications were lovastatin, paroxetine, insulin, hydrochlorothiazide, and lisinopril. Three weeks previously he had completed a 10‐day course of trimethoprim/sulfamethoxazole for an upper respiratory infection. Otherwise, he was taking no new medications. He was allergic to penicillin. He denied substance abuse, recent travel, or risk factors for human immunodeficiency virus (HIV) infection. He worked as an automobile painter, lived with his wife, and had a pet dog.

Physical examination revealed a well‐appearing man with normal vital signs. His skin had well‐defined circumscribed pink plaques, mostly 1‐2 cm in size, with thick, silvery scales in the ears and on the dorsal and ventral arms and legs, chest, back, face, and scalp. There were no pustules or other signs of infection (Figs. 1and 2). The nails exhibited distal onycholysis, oil spots, and rare pits. His posterior pharynx was mildly erythematous. The results of cardiovascular, pulmonary, and abdominal examinations were normal.

Figure 1

Figure 2

Although other scaling skin conditions such as eczema, irritant dermatitis, or malignancy remain possible, his rash is most consistent with widespread psoriasis. I would consider immunological changes that may have caused a remarkably altered and more severe expression of his chronic disease, for example, recent steroid therapy or HIV infection. The company a rash keeps helps frame the differential diagnosis. Based on the patient's well appearance, the time course, his minimal systemic symptoms, and the appearance of the rash, my leading considerations are psoriasis or an allergic dermatitis. Cutaneous T‐cell malignancy, with its indolent and sometimes protean manifestations, remains possible in a patient of his age. I would now consult a dermatologist for 3 reasons: this patient has a chronic disease that I do not manage beyond basic treatments (eg, topical steroids), he has an undiagnosed illness with substantial dermatologic manifestations, and he may need a skin biopsy for definitive diagnosis.

The dermatology team diagnosed a guttate psoriasis flare, possibly associated with streptococcal pharyngitis. The differential diagnosis included secondary syphilis, although the team believed this was less likely. The dermatology team recommended obtaining a throat culture, streptozyme assay, and rapid plasma reagin and prescribed oral erythromycin and topical steroid ointment under a sauna suit.

I would follow his response to the prescribed steroid treatments. If the patient's course deviates from the dermatologists' expectations, I would request a skin biopsy and undertake further evaluations in search of an underlying systemic disease.

The patient followed up in the dermatology clinic 3 weeks later. His rash had worsened, and he had developed patchy alopecia and progressive edema of the face, ears, and eyes. He denied mouth or tongue swelling, difficulty breathing, or hives. The streptozyme assay was positive, but the other laboratory test results were negative.

The dermatology team diagnosed a severely inflammatory psoriasis flare and prescribed an oral retinoid, acitretin, and referred him for ultraviolet light therapy. He was unable to travel for phototherapy, and acitretin was discontinued after 1 week because of elevated serum transaminase levels. The dermatologists then prescribed oral cyclosporine.

The progression of disease despite standard treatment suggests a nonpsoriatic condition. Although medications could cause the abnormal liver tests, so could another underlying illness that involves the liver. An infiltrative disorder of the skin with hair follicle destruction and local lymphedema could explain both alopecia and facial edema.

I am unable account for his clinical features with a single disease, so the differential remains broad, including severe psoriasis, an infiltrating cutaneous malignancy, or a toxic exposure. Arsenic poisoning causes hyperkeratotic skin lesions, although he lacks the associated gastrointestinal and neurological symptoms. I would not have added the potentially toxic cyclosporine.

When he returned to dermatology clinic 1 week later, his rash and facial swelling had worsened. He also reported muscle and joint aches, fatigue, lightheadedness, anorexia, nausea, abdominal pain, diarrhea, and dyspnea on exertion. He denied fever, chills, and night sweats.

He appeared ill and used a cane to arise and walk. His vital signs and oxygen saturation were normal. He had marked swelling of his face, diffuse erythema and swelling on the chest, and widespread scaly, erythematous plaques (Fig. 3). The proximal nail folds of his fingers were erythematous, with ragged cuticles. His abdomen was mildly distended, but the rest of the physical examination was normal.

Figure 3

He has become too systemically ill to attribute his condition to psoriasis. The nail findings suggest dermatomyositis, which could explain many of his findings. The diffuse erythema and his difficulty walking are consistent with its skin and muscle involvement. Dyspnea could be explained by dermatomyositis‐associated interstitial lung disease. A dermatomyositis‐associated hematological or solid malignancy could account for his multisystem ailments and functional decline. A point against dermatomyositis is the relatively explosive onset of his disease. He should be carefully examined for any motor weakness. With his progressive erythroderma, I am also concerned about an advancing cutaneous T‐cell lymphoma (with leukemic transformation).

Blood tests revealed the following values: white‐blood‐cell count, 8700/L; hematocrit, 46%; platelet count, 172,000/L; blood urea nitrogen, 26 mg/dL; creatinine, 1.0 mg/dL; glucose, 199 mg/dL; albumin, 3.1 g/dL; alkaline phosphatase, 172 U/L (normal range 45‐129); alanine aminotransferase, 75 U/L (normal range 0‐39 U/L); aspartate aminotransferase, 263 U/L (normal range 0‐37 U/L); total bilirubin, 1.1 mg/dL; prothrombin time, 16 seconds (normal range 11.7‐14.3 seconds), and serum creatinine, kinase, 4253 U/L (normal range 0‐194 U/L). HIV serology was negative. Urinalysis revealed trace protein. The results of chest radiographs and an electrocardiogram were normal.

The liver function tests results are consistent with medication effects or liver involvement in a systemic disease. The creatinine kinase elevation is consistent with a myopathy such as dermatomyositis. A skin biopsy would still be useful. Depending on those results, he may need a muscle biopsy, urine heavy metal testing, and computed tomography body imaging. Considering his transaminase and creatinine kinase elevations, I would discontinue lovastatin.

The patient was hospitalized. Further questioning revealed that he had typical Raynaud's phenomenon and odynophagia. A detailed neurological examination showed weakness (3/5) of the triceps and iliopsoas muscles and difficulty rising from a chair without using his arms. Dermatoscopic examination of the proximal nail folds showed dilated capillary loops and foci of hemorrhage.

Blood tests showed a lactate dehydrogenase level of 456 U/L (normal range 0‐249 U/L) and an aldolase of 38 U/L (normal range 1.2‐7.6 U/L). Tests for antinuclear antibodies, anti‐Jo antibody, and antimyeloperoxidase antibodies were negative. Two skin biopsies were interpreted by general pathology as consistent with partially treated psoriasis, whereas another showed nonspecific changes with minimal superficial perivascular lymphohistiocytic inflammation (Fig. 4). Lisinopril was discontinued because of its possible contribution to the facial edema.

Figure 4

Dermatomyositis is now the leading diagnosis. Characteristic features include his proximal muscle weakness, Raynaud's phenomenon, and dilated nailfold capillary loops. I am not overly dissuaded by the negative antinuclear antibodies, but because of additional atypical features (ie, extensive cutaneous edema, rapid onset, illness severity, prominent gastrointestinal symptoms), a confirmatory muscle biopsy is needed. Endoscopy of the proximal aerodigestive tract would help evaluate the odynophagia. There is little to suggest infection, malignancy, or metabolic derangement.

The inpatient medical team considered myositis related to retinoid or cyclosporine therapy. They discontinued cyclosporine and began systemic corticosteroid therapy. Within a few days, the patient's rash, muscle pain, and weakness improved, and the elevated transaminase and creatinine kinase levels decreased.

Dermatology recommended an evaluation for dermatomyositis‐associated malignancy, but the medicine team and rheumatology consultants, noting the lack of classic skin findings (heliotrope rash and Gottron's papules) and the uncharacteristically rapid onset and improvement of myositis, suggested delaying the evaluation until dermatomyositis was proven.

An immediate improvement in symptoms with steroids is nonspecific, often occurring in autoimmune, infectious, and neoplastic diseases. This juncture in the case is common in complex multisystem illnesses, where various consultants may arrive at differing conclusions. With both typical and atypical features of dermatomyositis, where should one set the therapeutic threshold, that is, the point where one ends testing, accepts a diagnosis, and initiates treatment? Several factors raise the level of certainty I would require. First, dermatomyositis is quite rare. Adding atypical features further increases the burden of proof for that illness. Second, the existence of alternative possibilities (admittedly of equal uncertainty) gives me some pause. Finally, the toxicity of the proposed treatments raises the therapeutic threshold. Acknowledging that empiric treatment may be indicated for a severely ill patient at a lower level of certainty, I would hesitate to commit a patient to long‐term steroids without being confident of the diagnosis. I would therefore require a muscle biopsy, or at least electromyography to support or exclude dermatomyositis.

The patient was discharged from the hospital on high‐dose prednisone. He underwent electromyography, which revealed inflammatory myopathic changes more apparent in the proximal than distal muscles. These findings were thought to be compatible with dermatomyositis, although the fibrillations and positive sharp waves characteristic of acute inflammation were absent, perhaps because of corticosteroid therapy.

The patient mistakenly stopped taking his prednisone. Within days, his weakness and skin rash worsened, and he developed nausea with vomiting. He returned to clinic, where his creatinine kinase level was again found to be elevated, and he was rehospitalized. Oral corticosteroid therapy was restarted with prompt improvement. On review of the original skin biopsies, a dermatopathologist observed areas of thickened dermal collagen and a superficial and deep perivascular lymphocytic infiltrate, both consistent with connective tissue disease.

These 3 additional findings (ie, electromyography results, temporally established steroid responsiveness, and the new skin biopsy interpretation) in aggregate support the diagnosis of dermatomyositis, but the nausea and vomiting are unusual. I would discuss these results with a rheumatologist and still request a confirmatory muscle biopsy. Because diagnosing dermatomyositis should prompt consideration of seeking an underlying malignancy in a patient of this age group, I would repeat a targeted history and physical examination along with age‐ and risk‐factor‐appropriate screening. If muscle biopsy results are not definitive, finding an underlying malignancy would lend support to dermatomyositis.

While hospitalized, the patient complained of continued odynophagia and was noted to have oral candidiasis. Upper endoscopy, undertaken to evaluate for esophageal candidiasis, revealed a mass at the gastroesophageal junction. Biopsy revealed gastric‐type adenocarcinoma. An abdominal computed tomography scan demonstrated 3 hypodense hepatic lesions, evidence of cirrhosis, and ascites. Cytology of paracentesis fluid revealed cells compatible with adenocarcinoma. The patient died in hospice care 2 weeks later.

At autopsy, he had metastatic gastric‐type adenocarcinoma. A muscle biopsy (Fig. 5) revealed muscle atrophy with small foci of lymphocytic infiltrates, most compatible with dermatomyositis. Another dermatopathologist reviewed the skin biopsies and noted interface dermatitis, which is typical of connective tissue diseases like dermatomyositis (Fig. 6A,B).

Figure 5

Figure 6

COMMENTARY

Dermatomyositis is an idiopathic inflammatory myopathy characterized by endomysial inflammation and muscle weakness and differentiated from other myopathies by the presence of a rash.1 Muscle disease may manifest with or precede the rash, but up to 40% of patients present with skin manifestations alone, an entity called amyopathic dermatomyositis.2 When present, the myositis generally develops over months, but the onset can be acute.1 The weakness is typically symmetrical and proximal,1 and many patients have oropharyngeal dysphagia.3

The characteristic rash is erythematous, symmetrical, and photodistributed.4 Classic cutaneous findings are the heliotrope rash (violaceous eyelid erythema), which is pathognomonic but uncommon, and the more common Gottron's papules (violaceous, slightly elevated papules and plaques on bony prominences and extensor surfaces, especially the knuckles).4 Other findings include periorbital edema, scalp dermatitis, poikiloderma (ie, hyperpigmentation, hypopigmentation, atrophy, and telangiectasia), periungual erythema, and dystrophic cuticles.2 The cutaneous manifestations of dermatomyositis may be similar to those of psoriasis, systemic lupus erythematosus, lichen planus, rosacea, polymorphous light eruption, drug eruption, atopic dermatitis, seborrheic dermatitis, or allergic contact dermatitis.4

Diagnosing dermatomyositis requires considering clinical, laboratory, electromyographical, and histological evidence, as there are no widely accepted, validated diagnostic criteria.1, 5 The diagnosis is usually suspected if there is a characteristic rash and symptoms of myositis (eg, proximal muscle weakness, myalgias, fatigue, or an inability to swallow). When the patient has an atypical rash, skin biopsy can differentiate dermatomyositis from other conditions, except lupus, which shares the key finding of interface dermatitis.2 The histological findings can be variable and subtle,6 so consultation with a dermatopathologist may be helpful.

Myositis may be confirmed by various studies. Most patients have elevated muscle enzymes (ie, creatinine kinase, aldolase, lactate dehydrogenase, or transaminases)1; for those who do not, magnetic resonance imaging can be helpful in detecting muscle involvement and locating the best site for muscle biopsy.7 Electromyography reveals nonspecific muscle membrane instability.8 Muscle biopsy shows muscle fiber necrosis, perifascicular atrophy, and perivascular and perifascicular lymphocytic infiltrates. These can be patchy, diminished by steroid use, and occasionally seen in noninflammatory muscular dystrophies.8 For a patient with typical myositis and a characteristic rash, muscle biopsy may be unnecessary.1

The clinical utility of serologic testing for diagnosing dermatomyositis is controversial.2 Myositis‐specific antibody testing is insensitive but specific; these antibodies include Jo‐1, an antisynthetase antibody that predicts incomplete response to therapy and lung involvement, and Mi‐2, which is associated with better response to therapy.2, 9, 10 The sensitivity and specificity of antinuclear antibodies are both approximately 60%.10

Patients with dermatomyositis have higher rates of cancers than age‐matched controls, and nearly 25% of patients are diagnosed with a malignancy at some point during the course of the disease.11 Malignancies are typically solid tumors that manifest within 3 years of the diagnosis,1214 although the increased risk may exist for at least 5 years.14 There is a 10‐fold higher risk of ovarian cancer in women with dermatomyositis.12, 15 Other associated malignancies include lung, gastric, colorectal, pancreatic, and breast carcinomas and non‐Hodgkin's lymphoma.14

Recommendations for screening affected patients for cancer have changed over the years, with increasing evidence of an association between dermatomyositis and malignancy and evolving improvements in diagnostic techniques.16 Many authorities recommend that all adult patients with dermatomyositis be evaluated for cancer, including a complete physical examination, basic hematological tests, age‐ and sex‐appropriate screening (eg, mammography, pap smear, and colonoscopy), and chest x‐ray.16 Some would add upper endoscopy; imaging of the chest, abdomen, and pelvis; gynecological examination; and serum CA‐125 level to better evaluate for the most common malignancies (ie, ovarian, gastric, lung, and pancreatic carcinomas and non‐Hodgkins lymphoma).12, 1720

In 19% of adults, dermatomyositis overlaps with other autoimmune disorders, usually systemic lupus erythematosus and systemic sclerosis.21 These manifest as Raynaud's phenomenon, arthritis, esophageal dysmotility, renal disease, or neuropathy.21 Other potentially serious systemic manifestations of dermatomyositis include proximal dysphagia from pharyngeal myopathy; distal dysphagia from esophageal dysmotility in systemic sclerosis overlap; pulmonary disease from autoimmune interstitial lung disease or aspiration; cardiac disease from conduction abnormalities, myocarditis, pericarditis, and valvular disease; and rhabdomyolysis.2

Treatment of dermatomyositis requires systemic immunosuppression with 1 or more agents. The prognosis of dermatomyositis is variable. Mortality at 5 years ranges from 23% to 73%. At least a third of patients are left with mild to severe disability.1 In addition to older age, predictors of poor outcome include male sex, dysphagia, longstanding symptoms before treatment, pulmonary or cardiac involvement, and presence of antisynthetase antibodies.22

Dermatomyositis is often treated in the outpatient setting, but there are many reasons for hospitalization. Complications of treatment, like infection or adverse effects of medications, could result in hospitalization. Treatment with intravenous pulse corticosteroids or IVIG may require inpatient administration if no infusion center is available. Other indications for inpatient evaluation include the consequences of various malignancies and the more severe expression of systemic complications of dermatomyositis (eg, dysphagia and pulmonary, cardiac, or renal disease).

Every parent knows the plaintive backseat whine, Are we there, yet? Clinicians may also experience this feeling when attempting to diagnose a perplexing illness, especially one that lacks a definitive diagnostic test. It was easy for this patient's doctors to assume initially that his new rash was a manifestation of his long‐standing psoriasis. Having done so, they could understandably attribute the subsequent findings to either evolution of this disease or to consequences of the prescribed treatments, rather than considering a novel diagnosis. Only when faced with new (or newly appreciated) findings suggesting myopathy did the clinicians (and our discussant) consider the diagnosis of dermatomyositis. Even then, the primary inpatient medical team and their consultants were unsure when they had sufficient evidence to be certain.

Several factors compounded the difficulty of making a diagnosis in this case: the clinicians were dealing with a rare disease; they were considering alternative diagnoses (ie, psoriasis or a toxic effect of medication); and the disease presented somewhat atypically. The clinicians initially failed to consider and then accept the correct diagnosis because the patient's rash was not classic, his biopsy was interpreted as nonspecific, and he lacked myositis at presentation. Furthermore, when the generalists sought expert assistance, they encountered a difference of opinion among the consultants. These complex situations should goad the clinician into carefully considering the therapeutic threshold, that is, the transition point from diagnostic testing to therapeutic intervention.23 With complex cases like this, it may be difficult to know when one has reached a strongly supported diagnosis, and frequently asking whether we are there yet may be appropriate.

A 62‐year‐old man with psoriasis for more than 30 years presented to the emergency department with a scaly, pruritic rash involving his face, trunk, and extremities that he had had for the past 10 days. The rash was spreading and not responding to application of clobetasol ointment, which had helped his psoriasis in the past. He also reported mild pharyngitis, headache, and myalgias.

A patient with a chronic skin condition presenting with a new rash means the clinician must consider whether it is an alternative manifestation of the chronic disorder or a new illness. Psoriasis takes many forms including guttate psoriasis, which presents with small, droplike plaques and frequently follows respiratory infections (particularly those caused by Streptococcus). Well‐controlled psoriasis rarely transforms after 3 decades, so I would consider other conditions. The tempo of illness makes certain life‐threatening syndromes, including Stevens‐Johnson, toxic shock, and purpura fulminans, unlikely. An allergic reaction, atopic dermatitis, or medication reaction is possible. Infections, either systemic (eg, syphilis) or dermatologic (eg, scabies), should be considered. Photosensitivity could involve the sun‐exposed areas, such as the extremities and face. Seborrheic dermatitis can cause scaling lesions of the face and trunk but not the extremities. Vasculitis merits consideration, but dependent regions are typically affected more than the head. Mycosis fungoides or a paraneoplastic phenomenon could cause a diffuse rash in this age group.

The patient had diabetes mellitus, hypertension, diverticulosis, and depression. Three months earlier he had undergone surgical drainage of a perirectal abscess. His usual medications were lovastatin, paroxetine, insulin, hydrochlorothiazide, and lisinopril. Three weeks previously he had completed a 10‐day course of trimethoprim/sulfamethoxazole for an upper respiratory infection. Otherwise, he was taking no new medications. He was allergic to penicillin. He denied substance abuse, recent travel, or risk factors for human immunodeficiency virus (HIV) infection. He worked as an automobile painter, lived with his wife, and had a pet dog.

Physical examination revealed a well‐appearing man with normal vital signs. His skin had well‐defined circumscribed pink plaques, mostly 1‐2 cm in size, with thick, silvery scales in the ears and on the dorsal and ventral arms and legs, chest, back, face, and scalp. There were no pustules or other signs of infection (Figs. 1and 2). The nails exhibited distal onycholysis, oil spots, and rare pits. His posterior pharynx was mildly erythematous. The results of cardiovascular, pulmonary, and abdominal examinations were normal.

Figure 1

Figure 2

Although other scaling skin conditions such as eczema, irritant dermatitis, or malignancy remain possible, his rash is most consistent with widespread psoriasis. I would consider immunological changes that may have caused a remarkably altered and more severe expression of his chronic disease, for example, recent steroid therapy or HIV infection. The company a rash keeps helps frame the differential diagnosis. Based on the patient's well appearance, the time course, his minimal systemic symptoms, and the appearance of the rash, my leading considerations are psoriasis or an allergic dermatitis. Cutaneous T‐cell malignancy, with its indolent and sometimes protean manifestations, remains possible in a patient of his age. I would now consult a dermatologist for 3 reasons: this patient has a chronic disease that I do not manage beyond basic treatments (eg, topical steroids), he has an undiagnosed illness with substantial dermatologic manifestations, and he may need a skin biopsy for definitive diagnosis.

The dermatology team diagnosed a guttate psoriasis flare, possibly associated with streptococcal pharyngitis. The differential diagnosis included secondary syphilis, although the team believed this was less likely. The dermatology team recommended obtaining a throat culture, streptozyme assay, and rapid plasma reagin and prescribed oral erythromycin and topical steroid ointment under a sauna suit.

I would follow his response to the prescribed steroid treatments. If the patient's course deviates from the dermatologists' expectations, I would request a skin biopsy and undertake further evaluations in search of an underlying systemic disease.

The patient followed up in the dermatology clinic 3 weeks later. His rash had worsened, and he had developed patchy alopecia and progressive edema of the face, ears, and eyes. He denied mouth or tongue swelling, difficulty breathing, or hives. The streptozyme assay was positive, but the other laboratory test results were negative.

The dermatology team diagnosed a severely inflammatory psoriasis flare and prescribed an oral retinoid, acitretin, and referred him for ultraviolet light therapy. He was unable to travel for phototherapy, and acitretin was discontinued after 1 week because of elevated serum transaminase levels. The dermatologists then prescribed oral cyclosporine.

The progression of disease despite standard treatment suggests a nonpsoriatic condition. Although medications could cause the abnormal liver tests, so could another underlying illness that involves the liver. An infiltrative disorder of the skin with hair follicle destruction and local lymphedema could explain both alopecia and facial edema.

I am unable account for his clinical features with a single disease, so the differential remains broad, including severe psoriasis, an infiltrating cutaneous malignancy, or a toxic exposure. Arsenic poisoning causes hyperkeratotic skin lesions, although he lacks the associated gastrointestinal and neurological symptoms. I would not have added the potentially toxic cyclosporine.

When he returned to dermatology clinic 1 week later, his rash and facial swelling had worsened. He also reported muscle and joint aches, fatigue, lightheadedness, anorexia, nausea, abdominal pain, diarrhea, and dyspnea on exertion. He denied fever, chills, and night sweats.

He appeared ill and used a cane to arise and walk. His vital signs and oxygen saturation were normal. He had marked swelling of his face, diffuse erythema and swelling on the chest, and widespread scaly, erythematous plaques (Fig. 3). The proximal nail folds of his fingers were erythematous, with ragged cuticles. His abdomen was mildly distended, but the rest of the physical examination was normal.

Figure 3

He has become too systemically ill to attribute his condition to psoriasis. The nail findings suggest dermatomyositis, which could explain many of his findings. The diffuse erythema and his difficulty walking are consistent with its skin and muscle involvement. Dyspnea could be explained by dermatomyositis‐associated interstitial lung disease. A dermatomyositis‐associated hematological or solid malignancy could account for his multisystem ailments and functional decline. A point against dermatomyositis is the relatively explosive onset of his disease. He should be carefully examined for any motor weakness. With his progressive erythroderma, I am also concerned about an advancing cutaneous T‐cell lymphoma (with leukemic transformation).

Blood tests revealed the following values: white‐blood‐cell count, 8700/L; hematocrit, 46%; platelet count, 172,000/L; blood urea nitrogen, 26 mg/dL; creatinine, 1.0 mg/dL; glucose, 199 mg/dL; albumin, 3.1 g/dL; alkaline phosphatase, 172 U/L (normal range 45‐129); alanine aminotransferase, 75 U/L (normal range 0‐39 U/L); aspartate aminotransferase, 263 U/L (normal range 0‐37 U/L); total bilirubin, 1.1 mg/dL; prothrombin time, 16 seconds (normal range 11.7‐14.3 seconds), and serum creatinine, kinase, 4253 U/L (normal range 0‐194 U/L). HIV serology was negative. Urinalysis revealed trace protein. The results of chest radiographs and an electrocardiogram were normal.

The liver function tests results are consistent with medication effects or liver involvement in a systemic disease. The creatinine kinase elevation is consistent with a myopathy such as dermatomyositis. A skin biopsy would still be useful. Depending on those results, he may need a muscle biopsy, urine heavy metal testing, and computed tomography body imaging. Considering his transaminase and creatinine kinase elevations, I would discontinue lovastatin.

The patient was hospitalized. Further questioning revealed that he had typical Raynaud's phenomenon and odynophagia. A detailed neurological examination showed weakness (3/5) of the triceps and iliopsoas muscles and difficulty rising from a chair without using his arms. Dermatoscopic examination of the proximal nail folds showed dilated capillary loops and foci of hemorrhage.

Blood tests showed a lactate dehydrogenase level of 456 U/L (normal range 0‐249 U/L) and an aldolase of 38 U/L (normal range 1.2‐7.6 U/L). Tests for antinuclear antibodies, anti‐Jo antibody, and antimyeloperoxidase antibodies were negative. Two skin biopsies were interpreted by general pathology as consistent with partially treated psoriasis, whereas another showed nonspecific changes with minimal superficial perivascular lymphohistiocytic inflammation (Fig. 4). Lisinopril was discontinued because of its possible contribution to the facial edema.

Figure 4

Dermatomyositis is now the leading diagnosis. Characteristic features include his proximal muscle weakness, Raynaud's phenomenon, and dilated nailfold capillary loops. I am not overly dissuaded by the negative antinuclear antibodies, but because of additional atypical features (ie, extensive cutaneous edema, rapid onset, illness severity, prominent gastrointestinal symptoms), a confirmatory muscle biopsy is needed. Endoscopy of the proximal aerodigestive tract would help evaluate the odynophagia. There is little to suggest infection, malignancy, or metabolic derangement.

The inpatient medical team considered myositis related to retinoid or cyclosporine therapy. They discontinued cyclosporine and began systemic corticosteroid therapy. Within a few days, the patient's rash, muscle pain, and weakness improved, and the elevated transaminase and creatinine kinase levels decreased.

Dermatology recommended an evaluation for dermatomyositis‐associated malignancy, but the medicine team and rheumatology consultants, noting the lack of classic skin findings (heliotrope rash and Gottron's papules) and the uncharacteristically rapid onset and improvement of myositis, suggested delaying the evaluation until dermatomyositis was proven.

An immediate improvement in symptoms with steroids is nonspecific, often occurring in autoimmune, infectious, and neoplastic diseases. This juncture in the case is common in complex multisystem illnesses, where various consultants may arrive at differing conclusions. With both typical and atypical features of dermatomyositis, where should one set the therapeutic threshold, that is, the point where one ends testing, accepts a diagnosis, and initiates treatment? Several factors raise the level of certainty I would require. First, dermatomyositis is quite rare. Adding atypical features further increases the burden of proof for that illness. Second, the existence of alternative possibilities (admittedly of equal uncertainty) gives me some pause. Finally, the toxicity of the proposed treatments raises the therapeutic threshold. Acknowledging that empiric treatment may be indicated for a severely ill patient at a lower level of certainty, I would hesitate to commit a patient to long‐term steroids without being confident of the diagnosis. I would therefore require a muscle biopsy, or at least electromyography to support or exclude dermatomyositis.

The patient was discharged from the hospital on high‐dose prednisone. He underwent electromyography, which revealed inflammatory myopathic changes more apparent in the proximal than distal muscles. These findings were thought to be compatible with dermatomyositis, although the fibrillations and positive sharp waves characteristic of acute inflammation were absent, perhaps because of corticosteroid therapy.

The patient mistakenly stopped taking his prednisone. Within days, his weakness and skin rash worsened, and he developed nausea with vomiting. He returned to clinic, where his creatinine kinase level was again found to be elevated, and he was rehospitalized. Oral corticosteroid therapy was restarted with prompt improvement. On review of the original skin biopsies, a dermatopathologist observed areas of thickened dermal collagen and a superficial and deep perivascular lymphocytic infiltrate, both consistent with connective tissue disease.

These 3 additional findings (ie, electromyography results, temporally established steroid responsiveness, and the new skin biopsy interpretation) in aggregate support the diagnosis of dermatomyositis, but the nausea and vomiting are unusual. I would discuss these results with a rheumatologist and still request a confirmatory muscle biopsy. Because diagnosing dermatomyositis should prompt consideration of seeking an underlying malignancy in a patient of this age group, I would repeat a targeted history and physical examination along with age‐ and risk‐factor‐appropriate screening. If muscle biopsy results are not definitive, finding an underlying malignancy would lend support to dermatomyositis.

While hospitalized, the patient complained of continued odynophagia and was noted to have oral candidiasis. Upper endoscopy, undertaken to evaluate for esophageal candidiasis, revealed a mass at the gastroesophageal junction. Biopsy revealed gastric‐type adenocarcinoma. An abdominal computed tomography scan demonstrated 3 hypodense hepatic lesions, evidence of cirrhosis, and ascites. Cytology of paracentesis fluid revealed cells compatible with adenocarcinoma. The patient died in hospice care 2 weeks later.

At autopsy, he had metastatic gastric‐type adenocarcinoma. A muscle biopsy (Fig. 5) revealed muscle atrophy with small foci of lymphocytic infiltrates, most compatible with dermatomyositis. Another dermatopathologist reviewed the skin biopsies and noted interface dermatitis, which is typical of connective tissue diseases like dermatomyositis (Fig. 6A,B).

Figure 5

Figure 6

COMMENTARY

Dermatomyositis is an idiopathic inflammatory myopathy characterized by endomysial inflammation and muscle weakness and differentiated from other myopathies by the presence of a rash.1 Muscle disease may manifest with or precede the rash, but up to 40% of patients present with skin manifestations alone, an entity called amyopathic dermatomyositis.2 When present, the myositis generally develops over months, but the onset can be acute.1 The weakness is typically symmetrical and proximal,1 and many patients have oropharyngeal dysphagia.3

The characteristic rash is erythematous, symmetrical, and photodistributed.4 Classic cutaneous findings are the heliotrope rash (violaceous eyelid erythema), which is pathognomonic but uncommon, and the more common Gottron's papules (violaceous, slightly elevated papules and plaques on bony prominences and extensor surfaces, especially the knuckles).4 Other findings include periorbital edema, scalp dermatitis, poikiloderma (ie, hyperpigmentation, hypopigmentation, atrophy, and telangiectasia), periungual erythema, and dystrophic cuticles.2 The cutaneous manifestations of dermatomyositis may be similar to those of psoriasis, systemic lupus erythematosus, lichen planus, rosacea, polymorphous light eruption, drug eruption, atopic dermatitis, seborrheic dermatitis, or allergic contact dermatitis.4

Diagnosing dermatomyositis requires considering clinical, laboratory, electromyographical, and histological evidence, as there are no widely accepted, validated diagnostic criteria.1, 5 The diagnosis is usually suspected if there is a characteristic rash and symptoms of myositis (eg, proximal muscle weakness, myalgias, fatigue, or an inability to swallow). When the patient has an atypical rash, skin biopsy can differentiate dermatomyositis from other conditions, except lupus, which shares the key finding of interface dermatitis.2 The histological findings can be variable and subtle,6 so consultation with a dermatopathologist may be helpful.

Myositis may be confirmed by various studies. Most patients have elevated muscle enzymes (ie, creatinine kinase, aldolase, lactate dehydrogenase, or transaminases)1; for those who do not, magnetic resonance imaging can be helpful in detecting muscle involvement and locating the best site for muscle biopsy.7 Electromyography reveals nonspecific muscle membrane instability.8 Muscle biopsy shows muscle fiber necrosis, perifascicular atrophy, and perivascular and perifascicular lymphocytic infiltrates. These can be patchy, diminished by steroid use, and occasionally seen in noninflammatory muscular dystrophies.8 For a patient with typical myositis and a characteristic rash, muscle biopsy may be unnecessary.1

The clinical utility of serologic testing for diagnosing dermatomyositis is controversial.2 Myositis‐specific antibody testing is insensitive but specific; these antibodies include Jo‐1, an antisynthetase antibody that predicts incomplete response to therapy and lung involvement, and Mi‐2, which is associated with better response to therapy.2, 9, 10 The sensitivity and specificity of antinuclear antibodies are both approximately 60%.10

Patients with dermatomyositis have higher rates of cancers than age‐matched controls, and nearly 25% of patients are diagnosed with a malignancy at some point during the course of the disease.11 Malignancies are typically solid tumors that manifest within 3 years of the diagnosis,1214 although the increased risk may exist for at least 5 years.14 There is a 10‐fold higher risk of ovarian cancer in women with dermatomyositis.12, 15 Other associated malignancies include lung, gastric, colorectal, pancreatic, and breast carcinomas and non‐Hodgkin's lymphoma.14

Recommendations for screening affected patients for cancer have changed over the years, with increasing evidence of an association between dermatomyositis and malignancy and evolving improvements in diagnostic techniques.16 Many authorities recommend that all adult patients with dermatomyositis be evaluated for cancer, including a complete physical examination, basic hematological tests, age‐ and sex‐appropriate screening (eg, mammography, pap smear, and colonoscopy), and chest x‐ray.16 Some would add upper endoscopy; imaging of the chest, abdomen, and pelvis; gynecological examination; and serum CA‐125 level to better evaluate for the most common malignancies (ie, ovarian, gastric, lung, and pancreatic carcinomas and non‐Hodgkins lymphoma).12, 1720

In 19% of adults, dermatomyositis overlaps with other autoimmune disorders, usually systemic lupus erythematosus and systemic sclerosis.21 These manifest as Raynaud's phenomenon, arthritis, esophageal dysmotility, renal disease, or neuropathy.21 Other potentially serious systemic manifestations of dermatomyositis include proximal dysphagia from pharyngeal myopathy; distal dysphagia from esophageal dysmotility in systemic sclerosis overlap; pulmonary disease from autoimmune interstitial lung disease or aspiration; cardiac disease from conduction abnormalities, myocarditis, pericarditis, and valvular disease; and rhabdomyolysis.2

Treatment of dermatomyositis requires systemic immunosuppression with 1 or more agents. The prognosis of dermatomyositis is variable. Mortality at 5 years ranges from 23% to 73%. At least a third of patients are left with mild to severe disability.1 In addition to older age, predictors of poor outcome include male sex, dysphagia, longstanding symptoms before treatment, pulmonary or cardiac involvement, and presence of antisynthetase antibodies.22

Dermatomyositis is often treated in the outpatient setting, but there are many reasons for hospitalization. Complications of treatment, like infection or adverse effects of medications, could result in hospitalization. Treatment with intravenous pulse corticosteroids or IVIG may require inpatient administration if no infusion center is available. Other indications for inpatient evaluation include the consequences of various malignancies and the more severe expression of systemic complications of dermatomyositis (eg, dysphagia and pulmonary, cardiac, or renal disease).

Every parent knows the plaintive backseat whine, Are we there, yet? Clinicians may also experience this feeling when attempting to diagnose a perplexing illness, especially one that lacks a definitive diagnostic test. It was easy for this patient's doctors to assume initially that his new rash was a manifestation of his long‐standing psoriasis. Having done so, they could understandably attribute the subsequent findings to either evolution of this disease or to consequences of the prescribed treatments, rather than considering a novel diagnosis. Only when faced with new (or newly appreciated) findings suggesting myopathy did the clinicians (and our discussant) consider the diagnosis of dermatomyositis. Even then, the primary inpatient medical team and their consultants were unsure when they had sufficient evidence to be certain.

Several factors compounded the difficulty of making a diagnosis in this case: the clinicians were dealing with a rare disease; they were considering alternative diagnoses (ie, psoriasis or a toxic effect of medication); and the disease presented somewhat atypically. The clinicians initially failed to consider and then accept the correct diagnosis because the patient's rash was not classic, his biopsy was interpreted as nonspecific, and he lacked myositis at presentation. Furthermore, when the generalists sought expert assistance, they encountered a difference of opinion among the consultants. These complex situations should goad the clinician into carefully considering the therapeutic threshold, that is, the transition point from diagnostic testing to therapeutic intervention.23 With complex cases like this, it may be difficult to know when one has reached a strongly supported diagnosis, and frequently asking whether we are there yet may be appropriate.

A 5 year‐old girl presented to an emergency department (ED) with a 2‐day history of more than 12 episodes of nonbilious emesis. She received intravenous (IV) promethazine and 400 cc of normal saline and was discharged home. When emesis recurred the next morning, her pediatrician referred her for admission to our hospital for further hydration. The patient had neither fever nor rash but did report periumbilical pain and a few loose stools. She did not receive any medications other than the single dose of promethazine. Parents denied other toxic ingestion. The patient's family members had had a diarrheal illness over the past days.

The patient was born at term, small for gestational age, with uncomplicated pregnancy and delivery. She had normal growth and development and previously had been healthy, although her mother reported several prior ED visits for vomiting, including emesis with upper respiratory illnesses (URIs). There was no family history of gastrointestinal, metabolic, or renal disease. The patient lived with her parents and brother and attended kindergarten.

On examination, her temperature was 98.6F, blood pressure was 103/66, heart rate was 88, and respiratory rate was 24. She weighed 17.8 kg and was 115 cm tall (35th and 75th percentiles, respectively). She was alert and cooperative. Her breath had a ketotic odor. She had somewhat sunken eyes and dry mucous membranes. Her neck was supple, without lymphadenopathy. Capillary refill time was 3 seconds. Her lungs were clear to auscultation. Her abdomen was soft, nontender to palpation, and nondistended, and bowel sounds were hyperactive. Liver and spleen were of normal size. There was no edema, clubbing, nor cyanosis in the extremities. The patient was very fair‐skinned and did not have rashes, bruises, or other skin lesions. The results of her neurologic exam were entirely normal. Initial serum chemistry results were: sodium, 140 mEq/L; potassium, 5.9 mEq/L (hemolyzed); chloride, 107 mEq/L; bicarbonate, 13 mEq/L; glucose, 52 mg/dL; BUN, 19 mg/dL; creatinine, 0.5 mg/dL; and calcium, 10.5 mg/dL. Other laboratory analyses were ordered including urinalysis (UA), serum lactate, stool culture, rotaviral test, and fecal white blood cell count.

RESULTS

Further laboratory analysis revealed a urine pH of 5.5, specific gravity of 1.023, and 3+ ketones, with an otherwise normal UA. Blood lactic acid and pyruvic acid levels were normal at 0.8 and 0.11 mmol/L, respectively. All stool studies were negative. Tests to determine plasma quantitative amino acid and urine quantitative organic acid levels were ordered. The clinical course was benign, with recovery and normalization of blood chemistry values within 24 hours of IV hydration. The patient was discharged home the next day. Results of biochemical genetics laboratory testing were available 5 days later (Table 1). Plasma amino acids showed a decreased level of alanine, with elevated levels of leucine, isoleucine, and valine. _L‐alloisoleucine, which is not normally in plasma but is pathognomic for maple syrup urine disease (MSUD), was detected. Urine organic acid test results were notable for ketonuria, with elevated branched‐chain 2‐hydroxy and 2‐oxo acids consistent with a diagnosis of MSUD (Table 1).

The patient has done very well on follow‐up. Modest restriction of protein intake was instituted (<2 g/kg daily), and approximately 1 month after hospitalization a trial of thiamine was started. Plasma amino acid and urine organic acids have been normal on subsequent testing while the patient has been clinically well. Whole‐body leucine oxidation was estimated by quantitation of ¹³CO₂ after administration of an oral bolus of 1‐¹³C‐leucine, following the protocol of Elsas et al.1 The enrichment of ¹³CO₂ indicated oxidation of approximately 11% of the administered leucine over 3 hours, which was at the lower end of the normal range, with no increase after thiamine supplementation for 1 month. The patient did have 2 episodes of vomiting associated with mild intercurrent illness 1 month and 1 year after hospitalization. Care was sought promptly at urgent care centers. Ketonuria was documented; however, no blood tests were ordered. There were no changes in mental status, and oral rehydration was successful. Molecular analysis of the branched chain ketoacid dehydrogenase complex E1, E1, and E2 subunit genes did not reveal any mutations in the coding regions, although 3 sequence variations were observed in E1 (2 silent changes, c.972C>T [Phe324Phe] and c.1221A>G [Leu407Leu], and c.376G>T [Gly126Cys], at this time of unclear significance).

DISCUSSION

We report the case of a young girl who presented with what was initially labeled simple gastroenteritis. It is important to note, however, that she had several days of repeated emesis, no fever, and minimal diarrhea, along with multiple previous episodes of vomiting illnesses requiring ED visits. Combined, these prompted further evaluation of her acidosis. Maple syrup urine disease, a congenital condition that can be lethal, went undiagnosed in this patient until this admission when she was 5 years old.

Metabolic Acidosis

Metabolic acidosis is a very common laboratory abnormality caused by 1 of 3 basic mechanisms: loss of bicarbonate, impaired renal acid excretion, or the addition of either endogenous or exogenous acids to the body. Common causes of nonanion gap metabolic acidosis in children include diarrhea and renal tubular acidosis (RTA). Increased anion gap is associated with lactic acidosis, ketoacidosis, and ingestion of such substances as methanol, ethylene glycol, acetylsalicylic acid, and bismuth subsalicylate. Inborn errors of metabolism cause production of ketoacids, lactic acid, and other organic anions. This can occur chronically or during acute decompensation with illness, stress, or therapy noncompliance.2 Serum anion gap, glucose, ketones, lactate, and ammonia can help to elucidate the specific etiology of metabolic acidosis (Fig. 1).

Figure 1

In our patient whose anion gap was at the upper limit of normal, both increased gap and non‐anion gap were considered as causes of the metabolic acidosis. Diarrhea was minimal, and there was no history of toxin or medication ingestion other than promethazine. RTA was unlikely given the borderline high serum anion gap and normal UA. Lactate level was normal, and examination did not find evidence of profound dehydration, both refuting that she had lactic acidosis severe enough to account for a serum bicarbonate of 13 mEq/L. Inborn errors of metabolism were therefore strongly considered.

A 5 year‐old girl presented to an emergency department (ED) with a 2‐day history of more than 12 episodes of nonbilious emesis. She received intravenous (IV) promethazine and 400 cc of normal saline and was discharged home. When emesis recurred the next morning, her pediatrician referred her for admission to our hospital for further hydration. The patient had neither fever nor rash but did report periumbilical pain and a few loose stools. She did not receive any medications other than the single dose of promethazine. Parents denied other toxic ingestion. The patient's family members had had a diarrheal illness over the past days.

The patient was born at term, small for gestational age, with uncomplicated pregnancy and delivery. She had normal growth and development and previously had been healthy, although her mother reported several prior ED visits for vomiting, including emesis with upper respiratory illnesses (URIs). There was no family history of gastrointestinal, metabolic, or renal disease. The patient lived with her parents and brother and attended kindergarten.

On examination, her temperature was 98.6F, blood pressure was 103/66, heart rate was 88, and respiratory rate was 24. She weighed 17.8 kg and was 115 cm tall (35th and 75th percentiles, respectively). She was alert and cooperative. Her breath had a ketotic odor. She had somewhat sunken eyes and dry mucous membranes. Her neck was supple, without lymphadenopathy. Capillary refill time was 3 seconds. Her lungs were clear to auscultation. Her abdomen was soft, nontender to palpation, and nondistended, and bowel sounds were hyperactive. Liver and spleen were of normal size. There was no edema, clubbing, nor cyanosis in the extremities. The patient was very fair‐skinned and did not have rashes, bruises, or other skin lesions. The results of her neurologic exam were entirely normal. Initial serum chemistry results were: sodium, 140 mEq/L; potassium, 5.9 mEq/L (hemolyzed); chloride, 107 mEq/L; bicarbonate, 13 mEq/L; glucose, 52 mg/dL; BUN, 19 mg/dL; creatinine, 0.5 mg/dL; and calcium, 10.5 mg/dL. Other laboratory analyses were ordered including urinalysis (UA), serum lactate, stool culture, rotaviral test, and fecal white blood cell count.

RESULTS

Further laboratory analysis revealed a urine pH of 5.5, specific gravity of 1.023, and 3+ ketones, with an otherwise normal UA. Blood lactic acid and pyruvic acid levels were normal at 0.8 and 0.11 mmol/L, respectively. All stool studies were negative. Tests to determine plasma quantitative amino acid and urine quantitative organic acid levels were ordered. The clinical course was benign, with recovery and normalization of blood chemistry values within 24 hours of IV hydration. The patient was discharged home the next day. Results of biochemical genetics laboratory testing were available 5 days later (Table 1). Plasma amino acids showed a decreased level of alanine, with elevated levels of leucine, isoleucine, and valine. _L‐alloisoleucine, which is not normally in plasma but is pathognomic for maple syrup urine disease (MSUD), was detected. Urine organic acid test results were notable for ketonuria, with elevated branched‐chain 2‐hydroxy and 2‐oxo acids consistent with a diagnosis of MSUD (Table 1).

The patient has done very well on follow‐up. Modest restriction of protein intake was instituted (<2 g/kg daily), and approximately 1 month after hospitalization a trial of thiamine was started. Plasma amino acid and urine organic acids have been normal on subsequent testing while the patient has been clinically well. Whole‐body leucine oxidation was estimated by quantitation of ¹³CO₂ after administration of an oral bolus of 1‐¹³C‐leucine, following the protocol of Elsas et al.1 The enrichment of ¹³CO₂ indicated oxidation of approximately 11% of the administered leucine over 3 hours, which was at the lower end of the normal range, with no increase after thiamine supplementation for 1 month. The patient did have 2 episodes of vomiting associated with mild intercurrent illness 1 month and 1 year after hospitalization. Care was sought promptly at urgent care centers. Ketonuria was documented; however, no blood tests were ordered. There were no changes in mental status, and oral rehydration was successful. Molecular analysis of the branched chain ketoacid dehydrogenase complex E1, E1, and E2 subunit genes did not reveal any mutations in the coding regions, although 3 sequence variations were observed in E1 (2 silent changes, c.972C>T [Phe324Phe] and c.1221A>G [Leu407Leu], and c.376G>T [Gly126Cys], at this time of unclear significance).

DISCUSSION

We report the case of a young girl who presented with what was initially labeled simple gastroenteritis. It is important to note, however, that she had several days of repeated emesis, no fever, and minimal diarrhea, along with multiple previous episodes of vomiting illnesses requiring ED visits. Combined, these prompted further evaluation of her acidosis. Maple syrup urine disease, a congenital condition that can be lethal, went undiagnosed in this patient until this admission when she was 5 years old.

Metabolic Acidosis

Metabolic acidosis is a very common laboratory abnormality caused by 1 of 3 basic mechanisms: loss of bicarbonate, impaired renal acid excretion, or the addition of either endogenous or exogenous acids to the body. Common causes of nonanion gap metabolic acidosis in children include diarrhea and renal tubular acidosis (RTA). Increased anion gap is associated with lactic acidosis, ketoacidosis, and ingestion of such substances as methanol, ethylene glycol, acetylsalicylic acid, and bismuth subsalicylate. Inborn errors of metabolism cause production of ketoacids, lactic acid, and other organic anions. This can occur chronically or during acute decompensation with illness, stress, or therapy noncompliance.2 Serum anion gap, glucose, ketones, lactate, and ammonia can help to elucidate the specific etiology of metabolic acidosis (Fig. 1).

Figure 1

In our patient whose anion gap was at the upper limit of normal, both increased gap and non‐anion gap were considered as causes of the metabolic acidosis. Diarrhea was minimal, and there was no history of toxin or medication ingestion other than promethazine. RTA was unlikely given the borderline high serum anion gap and normal UA. Lactate level was normal, and examination did not find evidence of profound dehydration, both refuting that she had lactic acidosis severe enough to account for a serum bicarbonate of 13 mEq/L. Inborn errors of metabolism were therefore strongly considered.

A 5 year‐old girl presented to an emergency department (ED) with a 2‐day history of more than 12 episodes of nonbilious emesis. She received intravenous (IV) promethazine and 400 cc of normal saline and was discharged home. When emesis recurred the next morning, her pediatrician referred her for admission to our hospital for further hydration. The patient had neither fever nor rash but did report periumbilical pain and a few loose stools. She did not receive any medications other than the single dose of promethazine. Parents denied other toxic ingestion. The patient's family members had had a diarrheal illness over the past days.

The patient was born at term, small for gestational age, with uncomplicated pregnancy and delivery. She had normal growth and development and previously had been healthy, although her mother reported several prior ED visits for vomiting, including emesis with upper respiratory illnesses (URIs). There was no family history of gastrointestinal, metabolic, or renal disease. The patient lived with her parents and brother and attended kindergarten.

On examination, her temperature was 98.6F, blood pressure was 103/66, heart rate was 88, and respiratory rate was 24. She weighed 17.8 kg and was 115 cm tall (35th and 75th percentiles, respectively). She was alert and cooperative. Her breath had a ketotic odor. She had somewhat sunken eyes and dry mucous membranes. Her neck was supple, without lymphadenopathy. Capillary refill time was 3 seconds. Her lungs were clear to auscultation. Her abdomen was soft, nontender to palpation, and nondistended, and bowel sounds were hyperactive. Liver and spleen were of normal size. There was no edema, clubbing, nor cyanosis in the extremities. The patient was very fair‐skinned and did not have rashes, bruises, or other skin lesions. The results of her neurologic exam were entirely normal. Initial serum chemistry results were: sodium, 140 mEq/L; potassium, 5.9 mEq/L (hemolyzed); chloride, 107 mEq/L; bicarbonate, 13 mEq/L; glucose, 52 mg/dL; BUN, 19 mg/dL; creatinine, 0.5 mg/dL; and calcium, 10.5 mg/dL. Other laboratory analyses were ordered including urinalysis (UA), serum lactate, stool culture, rotaviral test, and fecal white blood cell count.

RESULTS

Further laboratory analysis revealed a urine pH of 5.5, specific gravity of 1.023, and 3+ ketones, with an otherwise normal UA. Blood lactic acid and pyruvic acid levels were normal at 0.8 and 0.11 mmol/L, respectively. All stool studies were negative. Tests to determine plasma quantitative amino acid and urine quantitative organic acid levels were ordered. The clinical course was benign, with recovery and normalization of blood chemistry values within 24 hours of IV hydration. The patient was discharged home the next day. Results of biochemical genetics laboratory testing were available 5 days later (Table 1). Plasma amino acids showed a decreased level of alanine, with elevated levels of leucine, isoleucine, and valine. _L‐alloisoleucine, which is not normally in plasma but is pathognomic for maple syrup urine disease (MSUD), was detected. Urine organic acid test results were notable for ketonuria, with elevated branched‐chain 2‐hydroxy and 2‐oxo acids consistent with a diagnosis of MSUD (Table 1).

The patient has done very well on follow‐up. Modest restriction of protein intake was instituted (<2 g/kg daily), and approximately 1 month after hospitalization a trial of thiamine was started. Plasma amino acid and urine organic acids have been normal on subsequent testing while the patient has been clinically well. Whole‐body leucine oxidation was estimated by quantitation of ¹³CO₂ after administration of an oral bolus of 1‐¹³C‐leucine, following the protocol of Elsas et al.1 The enrichment of ¹³CO₂ indicated oxidation of approximately 11% of the administered leucine over 3 hours, which was at the lower end of the normal range, with no increase after thiamine supplementation for 1 month. The patient did have 2 episodes of vomiting associated with mild intercurrent illness 1 month and 1 year after hospitalization. Care was sought promptly at urgent care centers. Ketonuria was documented; however, no blood tests were ordered. There were no changes in mental status, and oral rehydration was successful. Molecular analysis of the branched chain ketoacid dehydrogenase complex E1, E1, and E2 subunit genes did not reveal any mutations in the coding regions, although 3 sequence variations were observed in E1 (2 silent changes, c.972C>T [Phe324Phe] and c.1221A>G [Leu407Leu], and c.376G>T [Gly126Cys], at this time of unclear significance).

DISCUSSION

We report the case of a young girl who presented with what was initially labeled simple gastroenteritis. It is important to note, however, that she had several days of repeated emesis, no fever, and minimal diarrhea, along with multiple previous episodes of vomiting illnesses requiring ED visits. Combined, these prompted further evaluation of her acidosis. Maple syrup urine disease, a congenital condition that can be lethal, went undiagnosed in this patient until this admission when she was 5 years old.

Metabolic Acidosis

Metabolic acidosis is a very common laboratory abnormality caused by 1 of 3 basic mechanisms: loss of bicarbonate, impaired renal acid excretion, or the addition of either endogenous or exogenous acids to the body. Common causes of nonanion gap metabolic acidosis in children include diarrhea and renal tubular acidosis (RTA). Increased anion gap is associated with lactic acidosis, ketoacidosis, and ingestion of such substances as methanol, ethylene glycol, acetylsalicylic acid, and bismuth subsalicylate. Inborn errors of metabolism cause production of ketoacids, lactic acid, and other organic anions. This can occur chronically or during acute decompensation with illness, stress, or therapy noncompliance.2 Serum anion gap, glucose, ketones, lactate, and ammonia can help to elucidate the specific etiology of metabolic acidosis (Fig. 1).

Figure 1

In our patient whose anion gap was at the upper limit of normal, both increased gap and non‐anion gap were considered as causes of the metabolic acidosis. Diarrhea was minimal, and there was no history of toxin or medication ingestion other than promethazine. RTA was unlikely given the borderline high serum anion gap and normal UA. Lactate level was normal, and examination did not find evidence of profound dehydration, both refuting that she had lactic acidosis severe enough to account for a serum bicarbonate of 13 mEq/L. Inborn errors of metabolism were therefore strongly considered.

When I was four years old, Grandpa always cut off the crust of the bread before I ate my peanut butter and jelly sandwich.

When I was seven years old, Grandpa took me to the circus and bought me cotton candy. He didn't care when I got the sticky stuff all over my face and dress.

When I was nine years old, Grandpa took me out on my birthday for a chocolate ice cream cone with rainbow sprinkles on top.

I didn't know he had high blood pressure. And neither did he.

He made me laugh. He made me feel so good deep down inside.

At age eleven I returned home from school to find Grandpa had been taken to the hospital with a stroke.

I cut the crust off his bread, got him cotton candy and an ice cream cone so he would feel better.

I went with Mommy to see him. She was stopped at the nurses' station. They wanted to talk to her.

I broke away and ran down the hall to his room. His bed was empty. Grandpa had died. No one told me.

Grandpa never got to eat the peanut butter and jelly sandwich with the crust cut off.

Maybe if he had, things would have turned out differently.

When I was four years old, Grandpa always cut off the crust of the bread before I ate my peanut butter and jelly sandwich.

When I was seven years old, Grandpa took me to the circus and bought me cotton candy. He didn't care when I got the sticky stuff all over my face and dress.

When I was nine years old, Grandpa took me out on my birthday for a chocolate ice cream cone with rainbow sprinkles on top.

I didn't know he had high blood pressure. And neither did he.

He made me laugh. He made me feel so good deep down inside.

At age eleven I returned home from school to find Grandpa had been taken to the hospital with a stroke.

I cut the crust off his bread, got him cotton candy and an ice cream cone so he would feel better.

I went with Mommy to see him. She was stopped at the nurses' station. They wanted to talk to her.

I broke away and ran down the hall to his room. His bed was empty. Grandpa had died. No one told me.

Grandpa never got to eat the peanut butter and jelly sandwich with the crust cut off.

Maybe if he had, things would have turned out differently.

When I was four years old, Grandpa always cut off the crust of the bread before I ate my peanut butter and jelly sandwich.

When I was seven years old, Grandpa took me to the circus and bought me cotton candy. He didn't care when I got the sticky stuff all over my face and dress.

When I was nine years old, Grandpa took me out on my birthday for a chocolate ice cream cone with rainbow sprinkles on top.

I didn't know he had high blood pressure. And neither did he.

He made me laugh. He made me feel so good deep down inside.

At age eleven I returned home from school to find Grandpa had been taken to the hospital with a stroke.

I cut the crust off his bread, got him cotton candy and an ice cream cone so he would feel better.

I went with Mommy to see him. She was stopped at the nurses' station. They wanted to talk to her.

I broke away and ran down the hall to his room. His bed was empty. Grandpa had died. No one told me.

Grandpa never got to eat the peanut butter and jelly sandwich with the crust cut off.

Maybe if he had, things would have turned out differently.

The most seriously ill medical patients are often admitted to an academic institution and taken care of on a teaching service.14 Previously published reports have found that, despite substantial differences in case mix, being admitted to a teaching hospital is associated with reduced morbidity and risk‐adjusted mortality for various conditions compared with receiving care delivered at a nonacademic hospital.2, 513 For example, among 248 major teaching, minor teaching, and nonteaching hospitals in New York state, Polanczyk et al. found that major teaching hospital status was an important determinant of outcomes in patients hospitalized with myocardial infarction, heart failure, or stroke.1

Some studies have noted that the high cost of care at teaching hospitals may offset these potential benefits.1, 6, 12, 13 In a retrospective analysis of 2674 Medicare patients, Taylor et al. determined that adjusted mortality rates were usually lower and Medicare payments usually higher in major teaching hospitals than in for‐profit hospitals.13 However, in a study of 80,851 patients admitted to 39 hospitals in northeastern Ohio, Rosenthal et al. reported both lower hospital mortality and shorter length of hospital stay (LOS) of patients admitted to major teaching hospitals than of patients admitted to nonteaching hospitals.12

Understanding the differences in economic and clinical outcomes between teaching and nonteaching medical services is topical in today's health care environment. Comparisons across institutions are inherently cumbersome because of the number of variables, other than teaching status, that can potentially contribute to differences in outcomes. A study comparing teaching and nonteaching services within a single institution could provide results unencumbered by such confounding factors. Accordingly, we sought to compare the teaching service with the nonteaching service at our academic community hospital to see if there were notable differences between the 2 services in case mix, costs, and clinical outcomes.

PATIENTS AND METHODS

Our analysis was based on administrative data for 2189 patients who were admitted to a 450‐bed university‐affiliated community hospital from February through October 2002 and assigned to 1 of the 3 teaching services staffed by residents in internal medicine and a faculty attending (n = 1637) or to a nonteaching service staffed by hospitalists or clinic‐based internists (n = 552).

Care on the nonteaching service was provided by 4 hospitalists and 12 clinic‐based internists. The nonteaching service generally had no interns or residents but occasionally had a third‐ or fourth‐year medical student on rotation. Care on the teaching services was provided under the supervision of 5 hospitalists and 18 clinic‐based internists. The day‐to‐day clinical decisions on the teaching services were made by the upper‐level resident (PGY‐2 or ‐3) assigned to the particular service, with the attending physicians acting in a supervisory role. Four of the 5 hospitalists rotated between nonteaching and teaching services. Cross‐coverage for teaching services was provided by other residents (by a night float team that rotated monthly), whereas a night attending only provided coverage for the nonteaching service. Patient handoffs occurred more commonly on the nonteaching service, where attendings rotated every 1‐2 weeks compared with the teaching services, where interns and residents rotated monthly and attendings changed every 2‐4 weeks.

All admissions to the medical services were screened and approved by either the chief medical resident or a designated faculty member who carried the departmental admission pager. Patients were randomly allocated to the respective teams based on patient load, in accordance with ACGME‐ and residency programimposed limits, rather than according to patient diagnoses. Differences between groups in severity of illness were minimized by limiting levels of acuity and including only patients admitted to the medical ward and not to the intensive care, coronary care, or intermediate care units. Patients on both model services were admitted to geographically shared wards with the same nursing staff and other ancillary personnel. All residents and faculty had similar access to hospital resources such as academic meetings, clinical protocols, practice‐based guidelines, and quality improvement initiatives.

The main outcome measures were total hospital costs; LOS; hospital readmission within 30 days; in‐hospital mortality; number of tests and procedures ordered; and pharmacy, laboratory, radiology, and procedural costs and costs for physical, speech, occupational, and respiratory therapy consultations. Financial data for patient care excluding physician fees were based on actual direct and indirect costs and were estimated using an activity‐based system (Transition Systems, Inc., Eclypsis Corporation, Boca Raton, FL). Department‐specific costs represented actual variable costs and did not include indirect (overhead) costs. Hospital length of stay was defined as the number of days from the time a patient was admitted to the general medicine service to the day discharged from the hospital, even if the patient was transferred to another service before discharge. Hospital readmission for the same primary diagnosis within 30 days after discharge was used to compare the quality of care on the 2 types of services.

We assessed the case mix on the 2 services by comparing the distribution of the 10 most frequent diagnosis‐related groups (DRGs) in the data set, plus angina, arrhythmia, and hypertension combined into a single category (Table 1). The chi‐square test was used to test differences between the 2 services in the proportion of each DRG. To obtain a surrogate index for case severity, the list of coexisting or comorbid conditions present at the time of admission was used to calculate the mean number of comorbidities per patient. The morbidity experience of the 2 patient populations was compared using the Student t test for 2 independent samples.

We compared the main outcome measures for teaching and nonteaching services using 3 analytic methods. First, the crude difference in total costs, service‐ and diagnosis‐specific costs, and length of hospital stay and the unadjusted odds ratio for readmission, in‐hospital mortality, and services ordered were calculated. The Student t test for 2 independent samples was used to compare total cost, LOS, and DRG‐specific and service‐specific costs. The chi‐square test was used to compare readmission rate, in‐hospital mortality, and number of services ordered. Second, we used multiple linear regression and logistic regression analyses to estimate the difference in the main outcome measures of the 2 medical services, adjusted for age, sex, insurance classification, number of comorbidities, and primary DRGs. The Wald test was used to obtain P values for testing differences between teaching and nonteaching services.

In observational studies, multiple linear regression models are commonly used to remove the effects of confounding factors. However, regression methods do not ensure the balance in the distribution of covariates, and imbalance becomes more problematic as the number of covariates increases. To manage the imbalance of case mix and other potential confounders, we used a propensity score method to balance confounding variables between the 2 groups.17 Specifically, by performing logistic regression with the potential confounding variables as covariates, we estimated the propensity score or the probability of being assigned to the teaching services for each patient (Tables 2 and 3). The collection of multiple characteristics was collapsed into a single composite score called the propensity score, and this score was used as if it were the only confounding variable. Patients were stratified to quintiles based on their propensity score, and the balance of the distribution of each potential confounder in the 5 propensity strata was checked, and we estimated the overall difference between the 2 medical services with the weighted average of the strata‐specific difference, where the weights were proportional to the stratum size. The Z test was used to derive P values for comparing the total hospital costs, LOS, and service‐specific costs of the 2 medical services. The Mantel‐Haenszel test was used to determine whether the 2 medical services had the same risk of readmission, death, and frequency of diagnostic or consultation services ordered. In all analyses we report P values without adjusting for multiple comparisons. The significance level of hypothesis testing was set at .05.

RESULTS

The study consisted of 2189 patients (1036 men) whose mean age was 67.2 years (SD = 19.0 years). Patient demographics and frequencies of various DRGs on the 2 services are shown in Table 1. The distribution of insurance classifications (eg, third‐party payer, Medicare, Medicaid, private pay) wase comparable between teaching and nonteaching groups. No statistically significant differences between the 2 services in patient characteristics and distribution of the 10 most common DRGs in the data set were observed except for patients with metabolic disorders (P = .01) and other respiratory infections (P = .03). The mean number of comorbidities was also comparable between teaching and nonteaching services (6.7 vs. 6.7; P = .99).

Care on the teaching service was not associated with a significant increase in overall costs per patient ($5572 vs. $5576, P = .99). Crude comparison of other main outcome measures showed that the LOS (4.92 vs. 5.10 days; P = .43), odds of readmission within 30 days (202/1637 vs. 57/552; P = .21), and odds of in‐hospital mortality (61/1637 vs. 25/552; P = .40) were comparable for teaching and nonteaching services (Tables 2 and 3). Using multiple linear regression analysis, the estimated adjusted differences were only $61 (P = .84) in overall costs and 0.13 days (P = .54) in LOS between teaching and nonteaching services. Estimated adjusted risk of readmission within 30 days was 25% higher (P = .17), and in‐hospital mortality was 24% lower (P = .28) for patients treated on the medical teaching services. Using the propensity score method, the estimated difference between teaching and nonteaching services was $130 (P = .70) in overall costs and 0.08 days (P = .73) in length of stay. Risk of readmission within 30 days was 26% higher (P = .15), and in‐hospital mortality was 18% lower (P = .41) for the teaching service. Because the distributions of overall costs and length of stay were heavily skewed, we also performed statistical analyses using logarithm‐transformed data on these 2 outcomes. The results using all 4 analytic methods showed that care on the teaching services was not associated with statistically significant differences in total hospital costs, LOS, risk of readmission, and in‐hospital mortality.

Service‐specific cost analyses showed that mean laboratory costs per patient ($937 vs. $810; P = .02) and mean radiology costs per patient ($134 vs. $96; P = .01) were higher for teaching services, whereas costs for the pharmacy ($233 vs. $229; P = .85) and for speech therapy ($2.4 vs. $2.4; P = .95), physical therapy ($6.6 vs. $7.2; P = .52), occupational therapy ($3.9 vs. $3.4; P = .43), respiratory therapy ($46 vs. $41; P = .42), pulmonary function testing ($0.4 vs. $0.4; P = .99), and GI endoscopy procedures ($5.9 vs. $5.8; P = .94) were not significantly different. A comparison of the number of consults or tests ordered indicated physicians on the teaching service did not order more radiology (1411/1637 vs. 471/552; P = .61), speech therapy (128/1637 vs. 37/552; P = .39), physical therapy (611/1637 vs. 207/552; P = .94), occupational therapy (369/1637 vs. 109/552; P = .17), respiratory therapy (893/1637 vs. 283/552; P = .19), or pulmonary function testing (75/1637 vs. 27/552; P = .89) consultations or GI endoscopy procedures (188/1637 vs. 65/552; P = .18). Inferential results derived by multiple linear regression and logistic regression analyses, as well as the propensity score method, all agreed with the results derived using crude comparisons and concluded that, except for laboratory and radiology costs, patients treated on the teaching services did not have higher service‐specific costs or more therapies and consultations.

To remove the potential confounding effects of the 5 hospitalists who rotated between teaching and nonteaching services, we removed 875 patients (125 on the nonteaching and 750 on the teaching service) from the original data set who were cared for by these physicians, and repeated crude, multivariate, and propensity score analyses. In the data subset (Tables 4 and 5), laboratory costs remained higher on the teaching service, but the difference in radiology costs between teaching and nonteaching services seen in the total data set diminished and did not remain statistically significant when hospitalists were excluded from the analysis.

DISCUSSION

We found that care delivered on the resident‐based teaching services at our academic community hospital was not associated with increases in overall costs, pharmacy costs, or consultative services ordered, although laboratory‐related costs and radiology costs were slightly higher than for the nonteaching service. In addition, clinical outcomes were not significantly different between teaching and nonteaching services in terms of hospital length of stay, in‐hospital mortality, and 30‐day readmission rate.

Several previous interinstitutional studies have documented greater utilization of resources at academic medical centers as a tradeoff for improved clinical outcomes.2, 4, 12, 13 One frequently offered explanation for higher costs at teaching hospitals is the purported tendency of resident physicians to order more tests and consults and to more heavily rely on modern diagnostic and therapeutic modalities. Apart from the number of tests and procedures ordered, differences in administrative, personnel, and other nonshared costs may account for higher overall costs at teaching hospitals reported in earlier studies. These variables, however, did not differ in our comparison of teaching and nonteaching services within the same institution because they were equally shared.

Studies that have looked at the hospitalist experience at academic centers and community hospitals have demonstrated improved efficiency associated with the use of hospitalist physicians.1517 At the University of Chicago, hospitalist care was associated with lower costs and short‐term mortality in the second year of hospitalist experience.15, 16 The authors suggested that disease‐specific physician experience in the hospitalist model may lead to reduced resource consumption and improved patient outcomes. The focus of our study was not a comparison of hospitalist with nonhospitalist models. However, when we excluded patients cared for by hospitalist physicians from our costs, services, and outcomes analyses, laboratory costs remained the only significant difference between teaching and nonteaching services.

Other than teaching hospital status and use of hospitalist physicians, institutional characteristics that can potentially influence clinical outcomes include hospital size, location, ownership, case mix, access to on‐site specialized diagnostic and therapeutic equipment, and availability of specialty services.15, 16 However, all these variables were identical in our study of teaching versus nonteaching services within the same community hospital, thereby allowing an uncontaminated estimation of the effect of teaching status on resource utilization and clinical outcomes. Although both teaching and nonteaching services were sometimes headed by attendings who participated in both models, teaching services differed notably in being run by resident team leaders with attendings performing a largely supervisory role.

We recognize several limitations of our study. Patients were quasirandomly triaged to teaching and nonteaching services according to patient loads without any consideration for diagnoses, comorbidities, or severity of illness. Therefore, it is quite possible there were unascertainable differences in disease severity and case mix between the teaching and nonteaching services. Notably, there was some discordance in the number of patients with nonpneumonia respiratory infection and the number with metabolic disorders assigned between the 2 services. However, 8 of the 10 most common primary diagnoses in the data set were similarly distributed between the 2 services, and the mean number of secondary diagnoses per patient was also not statistically different. More importantl we employed multiple regression analysis and a propensity score method to account for any imbalance in case mix and other potential confounders such as sex, age, and insurance classifications. These advanced statistical methods produced results similar to the unadjusted method and, hence, strengthen our conclusion that care delivered on the resident‐based teaching services at our academic community hospital was not significantly associated with increases in overall patient care costs, LOS, readmission rate, or in‐hospital mortality. Having hospitalist physicians on both teaching and nonteaching services may have had some effect on the practice patterns of other physicians, creating greater similarities than might have been expected otherwise. Data used in this study were obtained from only 1 academic institution, and caution should be exercised in extrapolating our findings to other settings unless substantiated by other studies.

The most seriously ill medical patients are often admitted to an academic institution and taken care of on a teaching service.14 Previously published reports have found that, despite substantial differences in case mix, being admitted to a teaching hospital is associated with reduced morbidity and risk‐adjusted mortality for various conditions compared with receiving care delivered at a nonacademic hospital.2, 513 For example, among 248 major teaching, minor teaching, and nonteaching hospitals in New York state, Polanczyk et al. found that major teaching hospital status was an important determinant of outcomes in patients hospitalized with myocardial infarction, heart failure, or stroke.1

Some studies have noted that the high cost of care at teaching hospitals may offset these potential benefits.1, 6, 12, 13 In a retrospective analysis of 2674 Medicare patients, Taylor et al. determined that adjusted mortality rates were usually lower and Medicare payments usually higher in major teaching hospitals than in for‐profit hospitals.13 However, in a study of 80,851 patients admitted to 39 hospitals in northeastern Ohio, Rosenthal et al. reported both lower hospital mortality and shorter length of hospital stay (LOS) of patients admitted to major teaching hospitals than of patients admitted to nonteaching hospitals.12

Understanding the differences in economic and clinical outcomes between teaching and nonteaching medical services is topical in today's health care environment. Comparisons across institutions are inherently cumbersome because of the number of variables, other than teaching status, that can potentially contribute to differences in outcomes. A study comparing teaching and nonteaching services within a single institution could provide results unencumbered by such confounding factors. Accordingly, we sought to compare the teaching service with the nonteaching service at our academic community hospital to see if there were notable differences between the 2 services in case mix, costs, and clinical outcomes.

PATIENTS AND METHODS

Our analysis was based on administrative data for 2189 patients who were admitted to a 450‐bed university‐affiliated community hospital from February through October 2002 and assigned to 1 of the 3 teaching services staffed by residents in internal medicine and a faculty attending (n = 1637) or to a nonteaching service staffed by hospitalists or clinic‐based internists (n = 552).

Care on the nonteaching service was provided by 4 hospitalists and 12 clinic‐based internists. The nonteaching service generally had no interns or residents but occasionally had a third‐ or fourth‐year medical student on rotation. Care on the teaching services was provided under the supervision of 5 hospitalists and 18 clinic‐based internists. The day‐to‐day clinical decisions on the teaching services were made by the upper‐level resident (PGY‐2 or ‐3) assigned to the particular service, with the attending physicians acting in a supervisory role. Four of the 5 hospitalists rotated between nonteaching and teaching services. Cross‐coverage for teaching services was provided by other residents (by a night float team that rotated monthly), whereas a night attending only provided coverage for the nonteaching service. Patient handoffs occurred more commonly on the nonteaching service, where attendings rotated every 1‐2 weeks compared with the teaching services, where interns and residents rotated monthly and attendings changed every 2‐4 weeks.

All admissions to the medical services were screened and approved by either the chief medical resident or a designated faculty member who carried the departmental admission pager. Patients were randomly allocated to the respective teams based on patient load, in accordance with ACGME‐ and residency programimposed limits, rather than according to patient diagnoses. Differences between groups in severity of illness were minimized by limiting levels of acuity and including only patients admitted to the medical ward and not to the intensive care, coronary care, or intermediate care units. Patients on both model services were admitted to geographically shared wards with the same nursing staff and other ancillary personnel. All residents and faculty had similar access to hospital resources such as academic meetings, clinical protocols, practice‐based guidelines, and quality improvement initiatives.

The main outcome measures were total hospital costs; LOS; hospital readmission within 30 days; in‐hospital mortality; number of tests and procedures ordered; and pharmacy, laboratory, radiology, and procedural costs and costs for physical, speech, occupational, and respiratory therapy consultations. Financial data for patient care excluding physician fees were based on actual direct and indirect costs and were estimated using an activity‐based system (Transition Systems, Inc., Eclypsis Corporation, Boca Raton, FL). Department‐specific costs represented actual variable costs and did not include indirect (overhead) costs. Hospital length of stay was defined as the number of days from the time a patient was admitted to the general medicine service to the day discharged from the hospital, even if the patient was transferred to another service before discharge. Hospital readmission for the same primary diagnosis within 30 days after discharge was used to compare the quality of care on the 2 types of services.

We assessed the case mix on the 2 services by comparing the distribution of the 10 most frequent diagnosis‐related groups (DRGs) in the data set, plus angina, arrhythmia, and hypertension combined into a single category (Table 1). The chi‐square test was used to test differences between the 2 services in the proportion of each DRG. To obtain a surrogate index for case severity, the list of coexisting or comorbid conditions present at the time of admission was used to calculate the mean number of comorbidities per patient. The morbidity experience of the 2 patient populations was compared using the Student t test for 2 independent samples.

We compared the main outcome measures for teaching and nonteaching services using 3 analytic methods. First, the crude difference in total costs, service‐ and diagnosis‐specific costs, and length of hospital stay and the unadjusted odds ratio for readmission, in‐hospital mortality, and services ordered were calculated. The Student t test for 2 independent samples was used to compare total cost, LOS, and DRG‐specific and service‐specific costs. The chi‐square test was used to compare readmission rate, in‐hospital mortality, and number of services ordered. Second, we used multiple linear regression and logistic regression analyses to estimate the difference in the main outcome measures of the 2 medical services, adjusted for age, sex, insurance classification, number of comorbidities, and primary DRGs. The Wald test was used to obtain P values for testing differences between teaching and nonteaching services.

In observational studies, multiple linear regression models are commonly used to remove the effects of confounding factors. However, regression methods do not ensure the balance in the distribution of covariates, and imbalance becomes more problematic as the number of covariates increases. To manage the imbalance of case mix and other potential confounders, we used a propensity score method to balance confounding variables between the 2 groups.17 Specifically, by performing logistic regression with the potential confounding variables as covariates, we estimated the propensity score or the probability of being assigned to the teaching services for each patient (Tables 2 and 3). The collection of multiple characteristics was collapsed into a single composite score called the propensity score, and this score was used as if it were the only confounding variable. Patients were stratified to quintiles based on their propensity score, and the balance of the distribution of each potential confounder in the 5 propensity strata was checked, and we estimated the overall difference between the 2 medical services with the weighted average of the strata‐specific difference, where the weights were proportional to the stratum size. The Z test was used to derive P values for comparing the total hospital costs, LOS, and service‐specific costs of the 2 medical services. The Mantel‐Haenszel test was used to determine whether the 2 medical services had the same risk of readmission, death, and frequency of diagnostic or consultation services ordered. In all analyses we report P values without adjusting for multiple comparisons. The significance level of hypothesis testing was set at .05.

RESULTS

The study consisted of 2189 patients (1036 men) whose mean age was 67.2 years (SD = 19.0 years). Patient demographics and frequencies of various DRGs on the 2 services are shown in Table 1. The distribution of insurance classifications (eg, third‐party payer, Medicare, Medicaid, private pay) wase comparable between teaching and nonteaching groups. No statistically significant differences between the 2 services in patient characteristics and distribution of the 10 most common DRGs in the data set were observed except for patients with metabolic disorders (P = .01) and other respiratory infections (P = .03). The mean number of comorbidities was also comparable between teaching and nonteaching services (6.7 vs. 6.7; P = .99).

Care on the teaching service was not associated with a significant increase in overall costs per patient ($5572 vs. $5576, P = .99). Crude comparison of other main outcome measures showed that the LOS (4.92 vs. 5.10 days; P = .43), odds of readmission within 30 days (202/1637 vs. 57/552; P = .21), and odds of in‐hospital mortality (61/1637 vs. 25/552; P = .40) were comparable for teaching and nonteaching services (Tables 2 and 3). Using multiple linear regression analysis, the estimated adjusted differences were only $61 (P = .84) in overall costs and 0.13 days (P = .54) in LOS between teaching and nonteaching services. Estimated adjusted risk of readmission within 30 days was 25% higher (P = .17), and in‐hospital mortality was 24% lower (P = .28) for patients treated on the medical teaching services. Using the propensity score method, the estimated difference between teaching and nonteaching services was $130 (P = .70) in overall costs and 0.08 days (P = .73) in length of stay. Risk of readmission within 30 days was 26% higher (P = .15), and in‐hospital mortality was 18% lower (P = .41) for the teaching service. Because the distributions of overall costs and length of stay were heavily skewed, we also performed statistical analyses using logarithm‐transformed data on these 2 outcomes. The results using all 4 analytic methods showed that care on the teaching services was not associated with statistically significant differences in total hospital costs, LOS, risk of readmission, and in‐hospital mortality.

Service‐specific cost analyses showed that mean laboratory costs per patient ($937 vs. $810; P = .02) and mean radiology costs per patient ($134 vs. $96; P = .01) were higher for teaching services, whereas costs for the pharmacy ($233 vs. $229; P = .85) and for speech therapy ($2.4 vs. $2.4; P = .95), physical therapy ($6.6 vs. $7.2; P = .52), occupational therapy ($3.9 vs. $3.4; P = .43), respiratory therapy ($46 vs. $41; P = .42), pulmonary function testing ($0.4 vs. $0.4; P = .99), and GI endoscopy procedures ($5.9 vs. $5.8; P = .94) were not significantly different. A comparison of the number of consults or tests ordered indicated physicians on the teaching service did not order more radiology (1411/1637 vs. 471/552; P = .61), speech therapy (128/1637 vs. 37/552; P = .39), physical therapy (611/1637 vs. 207/552; P = .94), occupational therapy (369/1637 vs. 109/552; P = .17), respiratory therapy (893/1637 vs. 283/552; P = .19), or pulmonary function testing (75/1637 vs. 27/552; P = .89) consultations or GI endoscopy procedures (188/1637 vs. 65/552; P = .18). Inferential results derived by multiple linear regression and logistic regression analyses, as well as the propensity score method, all agreed with the results derived using crude comparisons and concluded that, except for laboratory and radiology costs, patients treated on the teaching services did not have higher service‐specific costs or more therapies and consultations.

To remove the potential confounding effects of the 5 hospitalists who rotated between teaching and nonteaching services, we removed 875 patients (125 on the nonteaching and 750 on the teaching service) from the original data set who were cared for by these physicians, and repeated crude, multivariate, and propensity score analyses. In the data subset (Tables 4 and 5), laboratory costs remained higher on the teaching service, but the difference in radiology costs between teaching and nonteaching services seen in the total data set diminished and did not remain statistically significant when hospitalists were excluded from the analysis.

DISCUSSION

We found that care delivered on the resident‐based teaching services at our academic community hospital was not associated with increases in overall costs, pharmacy costs, or consultative services ordered, although laboratory‐related costs and radiology costs were slightly higher than for the nonteaching service. In addition, clinical outcomes were not significantly different between teaching and nonteaching services in terms of hospital length of stay, in‐hospital mortality, and 30‐day readmission rate.

Several previous interinstitutional studies have documented greater utilization of resources at academic medical centers as a tradeoff for improved clinical outcomes.2, 4, 12, 13 One frequently offered explanation for higher costs at teaching hospitals is the purported tendency of resident physicians to order more tests and consults and to more heavily rely on modern diagnostic and therapeutic modalities. Apart from the number of tests and procedures ordered, differences in administrative, personnel, and other nonshared costs may account for higher overall costs at teaching hospitals reported in earlier studies. These variables, however, did not differ in our comparison of teaching and nonteaching services within the same institution because they were equally shared.

Studies that have looked at the hospitalist experience at academic centers and community hospitals have demonstrated improved efficiency associated with the use of hospitalist physicians.1517 At the University of Chicago, hospitalist care was associated with lower costs and short‐term mortality in the second year of hospitalist experience.15, 16 The authors suggested that disease‐specific physician experience in the hospitalist model may lead to reduced resource consumption and improved patient outcomes. The focus of our study was not a comparison of hospitalist with nonhospitalist models. However, when we excluded patients cared for by hospitalist physicians from our costs, services, and outcomes analyses, laboratory costs remained the only significant difference between teaching and nonteaching services.

Other than teaching hospital status and use of hospitalist physicians, institutional characteristics that can potentially influence clinical outcomes include hospital size, location, ownership, case mix, access to on‐site specialized diagnostic and therapeutic equipment, and availability of specialty services.15, 16 However, all these variables were identical in our study of teaching versus nonteaching services within the same community hospital, thereby allowing an uncontaminated estimation of the effect of teaching status on resource utilization and clinical outcomes. Although both teaching and nonteaching services were sometimes headed by attendings who participated in both models, teaching services differed notably in being run by resident team leaders with attendings performing a largely supervisory role.

We recognize several limitations of our study. Patients were quasirandomly triaged to teaching and nonteaching services according to patient loads without any consideration for diagnoses, comorbidities, or severity of illness. Therefore, it is quite possible there were unascertainable differences in disease severity and case mix between the teaching and nonteaching services. Notably, there was some discordance in the number of patients with nonpneumonia respiratory infection and the number with metabolic disorders assigned between the 2 services. However, 8 of the 10 most common primary diagnoses in the data set were similarly distributed between the 2 services, and the mean number of secondary diagnoses per patient was also not statistically different. More importantl we employed multiple regression analysis and a propensity score method to account for any imbalance in case mix and other potential confounders such as sex, age, and insurance classifications. These advanced statistical methods produced results similar to the unadjusted method and, hence, strengthen our conclusion that care delivered on the resident‐based teaching services at our academic community hospital was not significantly associated with increases in overall patient care costs, LOS, readmission rate, or in‐hospital mortality. Having hospitalist physicians on both teaching and nonteaching services may have had some effect on the practice patterns of other physicians, creating greater similarities than might have been expected otherwise. Data used in this study were obtained from only 1 academic institution, and caution should be exercised in extrapolating our findings to other settings unless substantiated by other studies.

The most seriously ill medical patients are often admitted to an academic institution and taken care of on a teaching service.14 Previously published reports have found that, despite substantial differences in case mix, being admitted to a teaching hospital is associated with reduced morbidity and risk‐adjusted mortality for various conditions compared with receiving care delivered at a nonacademic hospital.2, 513 For example, among 248 major teaching, minor teaching, and nonteaching hospitals in New York state, Polanczyk et al. found that major teaching hospital status was an important determinant of outcomes in patients hospitalized with myocardial infarction, heart failure, or stroke.1

Some studies have noted that the high cost of care at teaching hospitals may offset these potential benefits.1, 6, 12, 13 In a retrospective analysis of 2674 Medicare patients, Taylor et al. determined that adjusted mortality rates were usually lower and Medicare payments usually higher in major teaching hospitals than in for‐profit hospitals.13 However, in a study of 80,851 patients admitted to 39 hospitals in northeastern Ohio, Rosenthal et al. reported both lower hospital mortality and shorter length of hospital stay (LOS) of patients admitted to major teaching hospitals than of patients admitted to nonteaching hospitals.12

Understanding the differences in economic and clinical outcomes between teaching and nonteaching medical services is topical in today's health care environment. Comparisons across institutions are inherently cumbersome because of the number of variables, other than teaching status, that can potentially contribute to differences in outcomes. A study comparing teaching and nonteaching services within a single institution could provide results unencumbered by such confounding factors. Accordingly, we sought to compare the teaching service with the nonteaching service at our academic community hospital to see if there were notable differences between the 2 services in case mix, costs, and clinical outcomes.

PATIENTS AND METHODS

Our analysis was based on administrative data for 2189 patients who were admitted to a 450‐bed university‐affiliated community hospital from February through October 2002 and assigned to 1 of the 3 teaching services staffed by residents in internal medicine and a faculty attending (n = 1637) or to a nonteaching service staffed by hospitalists or clinic‐based internists (n = 552).

Care on the nonteaching service was provided by 4 hospitalists and 12 clinic‐based internists. The nonteaching service generally had no interns or residents but occasionally had a third‐ or fourth‐year medical student on rotation. Care on the teaching services was provided under the supervision of 5 hospitalists and 18 clinic‐based internists. The day‐to‐day clinical decisions on the teaching services were made by the upper‐level resident (PGY‐2 or ‐3) assigned to the particular service, with the attending physicians acting in a supervisory role. Four of the 5 hospitalists rotated between nonteaching and teaching services. Cross‐coverage for teaching services was provided by other residents (by a night float team that rotated monthly), whereas a night attending only provided coverage for the nonteaching service. Patient handoffs occurred more commonly on the nonteaching service, where attendings rotated every 1‐2 weeks compared with the teaching services, where interns and residents rotated monthly and attendings changed every 2‐4 weeks.

All admissions to the medical services were screened and approved by either the chief medical resident or a designated faculty member who carried the departmental admission pager. Patients were randomly allocated to the respective teams based on patient load, in accordance with ACGME‐ and residency programimposed limits, rather than according to patient diagnoses. Differences between groups in severity of illness were minimized by limiting levels of acuity and including only patients admitted to the medical ward and not to the intensive care, coronary care, or intermediate care units. Patients on both model services were admitted to geographically shared wards with the same nursing staff and other ancillary personnel. All residents and faculty had similar access to hospital resources such as academic meetings, clinical protocols, practice‐based guidelines, and quality improvement initiatives.

The main outcome measures were total hospital costs; LOS; hospital readmission within 30 days; in‐hospital mortality; number of tests and procedures ordered; and pharmacy, laboratory, radiology, and procedural costs and costs for physical, speech, occupational, and respiratory therapy consultations. Financial data for patient care excluding physician fees were based on actual direct and indirect costs and were estimated using an activity‐based system (Transition Systems, Inc., Eclypsis Corporation, Boca Raton, FL). Department‐specific costs represented actual variable costs and did not include indirect (overhead) costs. Hospital length of stay was defined as the number of days from the time a patient was admitted to the general medicine service to the day discharged from the hospital, even if the patient was transferred to another service before discharge. Hospital readmission for the same primary diagnosis within 30 days after discharge was used to compare the quality of care on the 2 types of services.

We assessed the case mix on the 2 services by comparing the distribution of the 10 most frequent diagnosis‐related groups (DRGs) in the data set, plus angina, arrhythmia, and hypertension combined into a single category (Table 1). The chi‐square test was used to test differences between the 2 services in the proportion of each DRG. To obtain a surrogate index for case severity, the list of coexisting or comorbid conditions present at the time of admission was used to calculate the mean number of comorbidities per patient. The morbidity experience of the 2 patient populations was compared using the Student t test for 2 independent samples.

We compared the main outcome measures for teaching and nonteaching services using 3 analytic methods. First, the crude difference in total costs, service‐ and diagnosis‐specific costs, and length of hospital stay and the unadjusted odds ratio for readmission, in‐hospital mortality, and services ordered were calculated. The Student t test for 2 independent samples was used to compare total cost, LOS, and DRG‐specific and service‐specific costs. The chi‐square test was used to compare readmission rate, in‐hospital mortality, and number of services ordered. Second, we used multiple linear regression and logistic regression analyses to estimate the difference in the main outcome measures of the 2 medical services, adjusted for age, sex, insurance classification, number of comorbidities, and primary DRGs. The Wald test was used to obtain P values for testing differences between teaching and nonteaching services.

In observational studies, multiple linear regression models are commonly used to remove the effects of confounding factors. However, regression methods do not ensure the balance in the distribution of covariates, and imbalance becomes more problematic as the number of covariates increases. To manage the imbalance of case mix and other potential confounders, we used a propensity score method to balance confounding variables between the 2 groups.17 Specifically, by performing logistic regression with the potential confounding variables as covariates, we estimated the propensity score or the probability of being assigned to the teaching services for each patient (Tables 2 and 3). The collection of multiple characteristics was collapsed into a single composite score called the propensity score, and this score was used as if it were the only confounding variable. Patients were stratified to quintiles based on their propensity score, and the balance of the distribution of each potential confounder in the 5 propensity strata was checked, and we estimated the overall difference between the 2 medical services with the weighted average of the strata‐specific difference, where the weights were proportional to the stratum size. The Z test was used to derive P values for comparing the total hospital costs, LOS, and service‐specific costs of the 2 medical services. The Mantel‐Haenszel test was used to determine whether the 2 medical services had the same risk of readmission, death, and frequency of diagnostic or consultation services ordered. In all analyses we report P values without adjusting for multiple comparisons. The significance level of hypothesis testing was set at .05.