The Journal of Family Practice

The prevalence of allergic disease in the general population is quite high; 8.3% of adults and children have asthma and 11.4% of children have skin allergies.¹ Food allergies are present in 8% of children and 5% of adults,² and up to 10% of anaphylactic reactions in the United States are due to stinging insects.³

Allergy immunotherapy has been shown to produce a 2.7- to 13.7-fold overall improvement in hypersensitivity reactions.

Moderate-to-severe food and environmental allergies can negatively affect multiple organ systems and significantly impact morbidity and mortality.⁴ Quality of life and the financial well-being of patients with allergic diseases, as well as that of their families, can also be significantly impacted by these conditions.^4,5 High prevalence and burden of disease mandate that family physicians (FPs) stay up-to-date on the full array of treatment options for allergic diseases. What follows are 6 common questions about allergy immunotherapy (AIT) and the evidence-based answers that will help you to identify and treat appropriate candidates, as well as educate them along the way.

IMAGE: © ALICIA BUELOW

Who is a candidate for AIT?

Patients with moderate-to-severe immunoglobulin (Ig)E-mediated allergies whose symptoms are not adequately controlled by medications and allergen trigger avoidance are candidates for AIT.^6-8 Skin prick/puncture testing provides the most reliable and cost-effective confirmation of allergies that are suspected, based on patient history and clinical assessment for allergic symptoms.⁹ Life-threatening reactions to skin prick/puncture testing are rare.⁹ While in vitro (laboratory) testing for IgE levels to specific antigens may be more convenient for patients and less invasive than skin prick/puncture testing, it is also less sensitive and less reliable at quantifying the severity of sensitization.⁹

What constitutes AIT?

AIT is a disease-modifying treatment that, along with allergen avoidance, can provide long-term remission of allergic disease in certain circumstances.^6,7 Consistent gradual exposure to an allergen helps to dampen the inflammatory reaction driven by T cells and B cells, producing clinical tolerance or desensitization that persists after the discontinuation of AIT.⁸ While subcutaneous immunotherapy (SCIT) is the most widely known type of AIT (ie, allergy shots), there are additional ways that AIT can be administered. These include sublingual immunotherapy (SLIT), venom immunotherapy (VIT), and oral immunotherapy (OIT). The selection of the route of administration depends on the exact nature and symptoms of the allergic condition being treated (TABLE^6,8-12).

AIT involves 2 phases

The first phase is the induction or buildup phase during which patients are given gradually increasing amounts of allergen to induce a protective immunologic response.⁶ After 8 to 28 weeks, the maintenance phase begins, during which continued, consistent allergen exposure is designed to prevent relapse of, and facilitate continued remission of, allergy symptoms.⁶ The maintenance phase of AIT can last 24 to 48 months.^6,10 Certain patients may qualify for an expedited AIT regimen called cluster or rush immunotherapy.⁶

While lab testing may be more convenient for patients and less invasive than skin prick/ puncture testing, it is also less sensitive and less reliable at quantifying the severity of sensitization.

Conventional schedules for AIT involve increasing the dose of allergen given at each visit (1-3 doses/wk), whereas rush dosing involves multiple, increasing doses given in a single extended visit to reach therapeutic desensitization faster.⁶ AIT has been shown to produce a 2.7- to 13.7-fold overall improvement in hypersensitivity reactions.¹⁰

Length of therapy must be individualized

Experts recommend that the length of treatment with AIT be customized for each patient based on the severity of pretreatment allergy symptoms, the benefit experienced with AIT, the inconvenience of AIT to the patient, and the anticipated impact of symptom relapse.^6,10 There are no physiologic symptoms or objective tests that predict which patients will remain in remission after discontinuing AIT; thus, a joint task force of allergy experts suggests that the decision to restart AIT in patients who have a relapse in allergic symptoms should be made based on the same factors used to determine the duration of the maintenance phase.⁶

Continue to: These allergans are appropriate for AIT

Allergens may be described in terms of mechanism and chronicity of exposure. While avoidance of offending allergens is recommended for those who are sensitized, avoidance is not always possible.^6,7,9,13 AIT has been studied as a therapeutic modality to prevent exposure-related symptoms associated with each of the following types of allergens.^6,7,9,11,14

Inhalant allergens circulate in disturbed and undisturbed air and may be seasonal (eg, pollen), perennial (eg, cat/dog allergens), and/or occupational.⁹ They can derive from the indoors (eg, cockroach, cat, dog, dust mite) or outdoors (eg, tree, grass, or weed pollen ),^6,7,9,11 and serve as triggers for many allergic diseases such as allergic rhinitis (AR), allergic rhinoconjunctivitis, allergic dermatitis, and asthma.^7,13

Food allergens. Sensitization to food allergens may produce a range of symptoms.^6,7 One person may experience nothing more than tingling of the lips when eating a peach, while another may experience throat tightness and anaphylaxis due to the aroma of shellfish cooking.

Occupational allergens. Exposure to occupational allergens varies depending on the setting. Those who work in health care or with animals can be exposed to allergens (eg, latex and animal proteins, respectively) that can cause skin or respiratory hypersensitivity reactions. Occupational allergens can also include chemicals; workers in agriculture or housekeeping may be particularly at risk.

Insect allergens. Envenomation by stinging insects of the order Hymenoptera (bees, yellow jackets, hornets, wasps, fire ants) most commonly causes a pruritic, painful local reaction, but patients sensitized to Hymenoptera venom experience systemic allergic reactions that range from mild to life-threatening.^3,6,7

Continue to: When should you use AIT?

Allergic rhinitis (AR). AR can be triggered by exposure to indoor or outdoor inhalant allergens. Research has shown AIT to be an effective treatment for AR and the conjunctivitis caused by inhaled environmental allergens.^15-17 AIT results in improved symptom control and decreased use of rescue medication (standardized mean difference [SMD] -0.32; 95% confidence interval [CI], -0.23 to -0.33, favoring AIT intervention) in patients with seasonal or perennial AR.^15-17

SCIT effectiveness has been demonstrated in sensitized patients who have symptoms associated with pollen, animal allergens, dust mites, and mold/fungi,^15,16 and SCIT may be effective for the treatment of symptoms associated with cockroach exposure.¹¹ SLIT is approved by the US Food and Drug Administration (FDA) for the treatment of several pollen allergens with efficacy rates similar to those of SCIT and with no significant difference in adverse events (AEs).^8,15,16 Direct comparison studies of SCIT and SLIT preparations for treating grass allergy, while of low quality, showed comparable reductions in allergic rhinoconjunctival symptoms.¹⁵

Asthma. AIT (SCIT and SLIT) has been shown to be effective and safe in patients with mild-to-moderate asthma associated with inhalant allergens. Asthma should be controlled prior to initiation of AIT.^6,8,10 Well-known allergic triggers for asthma exacerbation include indoor inhaled allergens (eg, house dust mite, animal dander, cockroach), outdoor inhalant allergens (plants, pollen), and occupational inhaled allergens (silkworm, weevil).^11,13

In one meta-analysis of 796 patients with asthma from 19 different randomized controlled trials, SCIT significantly decreased asthma-related symptom scores (SMD = -0.94; 95% CI, -1.58 to -0.29; P = .004), as well as asthma medication scores (SMD = -1.06; 95% CI, -1.70 to -0.42; P = .001).¹⁸ While AIT has not been shown to improve lung function, meta-analyses have shown that adults with asthma treated with AIT experience fewer/less severe exacerbations and use less rescue medication when compared with those taking placebo.^19,20 Furthermore, studies have shown that SCIT and SLIT reduce asthma symptoms and asthma medication use compared with placebo or usual care in the pediatric population.²⁰

Adults with asthma treated with allergy immunotherapy use less rescue medication when compared to those taking placebo.

As helpful as AIT can be for some patients with mild-to-moderate asthma, patients with severe asthma experience more severe adverse reactions with AIT.²¹ Therefore, most experts recommend against administering AIT to patients with severe asthma.^6,8,21

Continue to: Stinging insects

Stinging insects. VIT is used for patients with hypersensitivity to the venom from insects of the order Hymenoptera (see previous list of insects).^3,11,22 A meta-analysis concluded, based on limited evidence from low-quality studies, that VIT has the potential to substantially reduce the incidence of severe allergic reactions in patients with Hymenoptera sensitivity with 72% of patients benefitting from VIT (number needed to treat [NNT] = 1.4).²² VIT reduces the risk of a systemic reaction, as well as the size and duration of large local reactions (LLRs).^6,22 Immunotherapy for stinging insects also has been shown to improve disease-specific quality of life (risk difference = 1.41 strongly favoring VIT).^6,22

Insect allergens. Research has shown AIT to be an effective therapy for many allergens even though the potency and effectiveness for some allergens are not standardized or regulated.^6,7,11,14 For example, AIT is available for some inhaled insect allergens; however, because the extracts are not standardized, AIT produces inconsistent outcomes.^11,14 As another example, certain occupations lead to exposure to inhaled insect allergens such as silkworm and weevils. AIT is not indicated for either because available silkworm extracts are used only for allergy testing.¹¹ There are no extracts to test for or treat weevil allergy.¹¹

Food. IgE-mediated food allergy can result in oral allergy syndrome, angioedema, urticaria, and/or anaphylaxis.^2,7,8 There is some evidence that AIT raises the threshold of reactivity in children with IgE-mediated food allergies.^6,7,23-25 But the studies available for meta-analyses (some of which involved OIT) were deemed to be of low quality due to a high risk of bias and a small number of participants.^24,25 AIT for food allergies is associated with a substantially increased incidence of moderate adverse reactions, including upper respiratory, gastrointestinal, and skin symptoms, with a probability of 46% during the buildup phase and a number needed to harm (NNH) of 2.1 (95% CI, 1.8-2.5; P < .0001).^6,25 Therefore, experts consider AIT in any form for food hypersensitivity to be investigational.^6,10

Allergen immunotherapy for allergic rhinitis has proven to be effective at improving quality of life and symptom control and decreasing comorbid disease and use of rescue medication.

But preliminary data from a recent phase 3 trial of OIT for peanut allergy involving 499 children and teens are promising; 67.2% tolerated the food challenge of ≥ 600 mg of peanut protein at the completion of peanut OIT without dose-limiting symptoms (difference = 63.2 percentage points; 95% CI, 53-73.3; P < .001).²⁶ More than twice as many participants in the placebo group vs the treatment group experienced AEs that were moderate (59% vs 25%, respectively) or severe (11% vs 5%, respectively).

There are ongoing trials of SCIT, SLIT, and OIT using modified food allergens to make participants less allergic while maintaining immunogenicity.^2,27 Additional trials include adjunctive treatments like probiotics to create safer, more effective options for children with food allergies.^2,27 Keep in mind that children with food allergies often have concomitant allergies (eg, inhalant allergies) that can benefit from AIT.

Continue to: Other clinical practice strategies include...

Other clinical practice strategies include the introduction of extensively heated (baked) milk and egg products, which benefit the majority of milk- and egg-allergic children.^2,28 An American Academy of Allergy, Asthma and Immunology (AAAAI)-sponsored Task Force and the European Academy of Allergy and Clinical Immunology (EAACI) support exclusive breastfeeding for the first 4 to 6 months of life to decrease the risk of developing food allergies.^6,7

Atopic dermatitis (AD). AD is an IgE-mediated skin disease that affects children and adults. AD is associated with asthma, AR, and food allergy.¹³ Early studies showed that AIT reduced topical corticosteroid use and improved the SCORAD (SCORing Atopic Dermatitis; see www.scorad.corti.li/) score.¹⁰ However, Cochrane reviews of studies involving children and adults with AD undergoing AIT via SCIT, SLIT, or OIT routes found that AIT was not effective in treating AD when accounting for the quality and heterogeneity of the studies.^12,29 In addition, there were no significant differences in SCORAD scores.^10,12

Contact allergens. Contact allergens, including plant resins (eg, poison ivy) and metals (eg, nickel) cause local dermatitis through a cell-mediated, delayed hypersensitivity response. AIT is not indicated for contact dermatitis.^6,9

Why use AIT?

First, AIT has been shown to modify disease. Second, because of its disease-modifying properties, AIT may provide cost savings over standard drug treatment in patients with asthma and AR.^17,20,30 In fact, individual studies have demonstrated ≥ 80% cost savings of AIT over standard drug regimens, although meta-analyses have been unable to demonstrate the same.^30,31

In addition, initial studies suggested that AIT might help to prevent the development of new allergen sensitizations.³² One meta-analysis found that AIT decreased the short-term risk of developing asthma in children with AR; however, subsequent studies showed that AIT did not have efficacy in preventing new allergic disease.^31,33

Continue to: How do you administer AIT?

FPs may be asked to administer AIT to their patients. Patients will typically have weekly office visits during the induction phase of AIT and should have appointments every 6 to 12 months during the maintenance phase.^6,8

While allergy immunotherapy has not been shown to improve lung function in patients with asthma, studies have shown that patients experience fewer exacerbations.

Collaboration with an allergy specialist is wise for dosing schedules and possibly for information regarding adverse reactions during administration. It is essential that AIT be administered by clinicians who are knowledgeable about the signs and symptoms of minor allergic reactions (eg, pruritus, mild erythema, and swelling at the administration site) and severe ones (eg, angioedema, shock, anaphylaxis), as well as who have immediate access to emergency medications and resuscitation, should it be needed.^6-8,34

Most (86%) adverse reactions will occur within 30 minutes of administration of AIT; hence, the recommendation is to observe patients for 30 minutes following AIT administration.^6,7,34 Continual training and “mock” severe reaction responses are beneficial for staff administering AIT to ensure appropriate equipment is available and that appropriate procedures are followed. Late-phase reactions can occur and usually present within 6 to 12 hours of administration; thus, it is essential for patients to be educated on the signs and symptoms of adverse reactions and on symptomatic and emergent treatment.^9,34

Experts consider allergy immunotherapy in any form for food hypersensitivity to be investigational.

Rush immunotherapy regimens for inhalant allergens are associated with increased AEs; therefore, pretreatment with antihistamines, leukotriene antagonists, the monoclonal antibody omalizumab, corticosteroids, or combinations of these agents is often used.^6,34 In contrast to inhaled allergens, rush VIT has not been associated with an increased risk of adverse reactions in meta-analyses.^6,22,34 Most experts recommend that AIT be discontinued if anaphylaxis occurs.^8,34

Is AIT safe?

AIT is a proven safe and effective disease-modifying treatment option.^6-8,31,35 Even when AIT is initiated within the season of increased allergen exposure, meta-analyses reveal no increase in adverse events in patients undergoing AIT.³⁵ Given the lack of high-quality evidence confirming the safety of AIT in the following specific situations, both the AAAAI and EAACI have concluded that these conditions/situations are absolute contraindications for AIT due to the risk of severe reactions by activation of underlying disease^8,21,36:

• severe asthma;
• acquired immune deficiency syndrome (AIDS); and
• initiation of AIT during pregnancy.

Continue to: Patients with a history of transplantation...

Patients with a history of transplantation, cancer in remission, human immunodeficiency virus (HIV) without AIDS, and cardiovascular disease have been safely treated with AIT with a < 1.5% incidence of serious adverse events.^6,21,36 It is possible to give patients taking beta-blockers and/or angiotensin converting enzyme inhibitors (ACEIs) AIT with appropriate consideration. Both classes of drugs can interfere with emergency treatment, so one should consider substitution with an agent from another class if possible during AIT.^6,8,20,34 Patients taking ACEIs receiving VIT had substantially increased adverse reactions compared with other forms of AIT; thus, individual risks and benefits must be weighed carefully before initiating VIT.^6,34

Looking ahead

Studies evaluating the indications for AIT in oral allergy syndrome, food allergy, latex allergy, AD, and venom allergy are ongoing.^2,7,10,26 Although the incidence of severe adverse allergy reactions during AIT is rare, there are investigations of using various immune-modifying agents to improve the safety and efficacy of AIT.³⁷ Application of allergen preparation using skin patches, intralymphatic injections, and chemically modified allergens to make them less immunologically reactive are being researched to further improve safety profiles and make AIT less time consuming.³⁸ In Europe and the United States, there is a call for more rigid studies using standardized SLIT preparations. This will allow for an increased number of AIT studies with decreased heterogeneity.

CORRESPONDENCE
Dellyse Bright, MD, Carolinas Medical Center Family Medicine Residency Program, Atrium Health, 2001 Vail Avenue, Suite 400B, Charlotte, NC 28207; Dellyse.Bright@atriumhealth.org.

The prevalence of allergic disease in the general population is quite high; 8.3% of adults and children have asthma and 11.4% of children have skin allergies.¹ Food allergies are present in 8% of children and 5% of adults,² and up to 10% of anaphylactic reactions in the United States are due to stinging insects.³

Allergy immunotherapy has been shown to produce a 2.7- to 13.7-fold overall improvement in hypersensitivity reactions.

Moderate-to-severe food and environmental allergies can negatively affect multiple organ systems and significantly impact morbidity and mortality.⁴ Quality of life and the financial well-being of patients with allergic diseases, as well as that of their families, can also be significantly impacted by these conditions.^4,5 High prevalence and burden of disease mandate that family physicians (FPs) stay up-to-date on the full array of treatment options for allergic diseases. What follows are 6 common questions about allergy immunotherapy (AIT) and the evidence-based answers that will help you to identify and treat appropriate candidates, as well as educate them along the way.

IMAGE: © ALICIA BUELOW

Who is a candidate for AIT?

Patients with moderate-to-severe immunoglobulin (Ig)E-mediated allergies whose symptoms are not adequately controlled by medications and allergen trigger avoidance are candidates for AIT.^6-8 Skin prick/puncture testing provides the most reliable and cost-effective confirmation of allergies that are suspected, based on patient history and clinical assessment for allergic symptoms.⁹ Life-threatening reactions to skin prick/puncture testing are rare.⁹ While in vitro (laboratory) testing for IgE levels to specific antigens may be more convenient for patients and less invasive than skin prick/puncture testing, it is also less sensitive and less reliable at quantifying the severity of sensitization.⁹

What constitutes AIT?

AIT is a disease-modifying treatment that, along with allergen avoidance, can provide long-term remission of allergic disease in certain circumstances.^6,7 Consistent gradual exposure to an allergen helps to dampen the inflammatory reaction driven by T cells and B cells, producing clinical tolerance or desensitization that persists after the discontinuation of AIT.⁸ While subcutaneous immunotherapy (SCIT) is the most widely known type of AIT (ie, allergy shots), there are additional ways that AIT can be administered. These include sublingual immunotherapy (SLIT), venom immunotherapy (VIT), and oral immunotherapy (OIT). The selection of the route of administration depends on the exact nature and symptoms of the allergic condition being treated (TABLE^6,8-12).

AIT involves 2 phases

The first phase is the induction or buildup phase during which patients are given gradually increasing amounts of allergen to induce a protective immunologic response.⁶ After 8 to 28 weeks, the maintenance phase begins, during which continued, consistent allergen exposure is designed to prevent relapse of, and facilitate continued remission of, allergy symptoms.⁶ The maintenance phase of AIT can last 24 to 48 months.^6,10 Certain patients may qualify for an expedited AIT regimen called cluster or rush immunotherapy.⁶

While lab testing may be more convenient for patients and less invasive than skin prick/ puncture testing, it is also less sensitive and less reliable at quantifying the severity of sensitization.

Conventional schedules for AIT involve increasing the dose of allergen given at each visit (1-3 doses/wk), whereas rush dosing involves multiple, increasing doses given in a single extended visit to reach therapeutic desensitization faster.⁶ AIT has been shown to produce a 2.7- to 13.7-fold overall improvement in hypersensitivity reactions.¹⁰

Length of therapy must be individualized

Experts recommend that the length of treatment with AIT be customized for each patient based on the severity of pretreatment allergy symptoms, the benefit experienced with AIT, the inconvenience of AIT to the patient, and the anticipated impact of symptom relapse.^6,10 There are no physiologic symptoms or objective tests that predict which patients will remain in remission after discontinuing AIT; thus, a joint task force of allergy experts suggests that the decision to restart AIT in patients who have a relapse in allergic symptoms should be made based on the same factors used to determine the duration of the maintenance phase.⁶

Continue to: These allergans are appropriate for AIT

Allergens may be described in terms of mechanism and chronicity of exposure. While avoidance of offending allergens is recommended for those who are sensitized, avoidance is not always possible.^6,7,9,13 AIT has been studied as a therapeutic modality to prevent exposure-related symptoms associated with each of the following types of allergens.^6,7,9,11,14

Inhalant allergens circulate in disturbed and undisturbed air and may be seasonal (eg, pollen), perennial (eg, cat/dog allergens), and/or occupational.⁹ They can derive from the indoors (eg, cockroach, cat, dog, dust mite) or outdoors (eg, tree, grass, or weed pollen ),^6,7,9,11 and serve as triggers for many allergic diseases such as allergic rhinitis (AR), allergic rhinoconjunctivitis, allergic dermatitis, and asthma.^7,13

Food allergens. Sensitization to food allergens may produce a range of symptoms.^6,7 One person may experience nothing more than tingling of the lips when eating a peach, while another may experience throat tightness and anaphylaxis due to the aroma of shellfish cooking.

Occupational allergens. Exposure to occupational allergens varies depending on the setting. Those who work in health care or with animals can be exposed to allergens (eg, latex and animal proteins, respectively) that can cause skin or respiratory hypersensitivity reactions. Occupational allergens can also include chemicals; workers in agriculture or housekeeping may be particularly at risk.

Insect allergens. Envenomation by stinging insects of the order Hymenoptera (bees, yellow jackets, hornets, wasps, fire ants) most commonly causes a pruritic, painful local reaction, but patients sensitized to Hymenoptera venom experience systemic allergic reactions that range from mild to life-threatening.^3,6,7

Continue to: When should you use AIT?

Allergic rhinitis (AR). AR can be triggered by exposure to indoor or outdoor inhalant allergens. Research has shown AIT to be an effective treatment for AR and the conjunctivitis caused by inhaled environmental allergens.^15-17 AIT results in improved symptom control and decreased use of rescue medication (standardized mean difference [SMD] -0.32; 95% confidence interval [CI], -0.23 to -0.33, favoring AIT intervention) in patients with seasonal or perennial AR.^15-17

SCIT effectiveness has been demonstrated in sensitized patients who have symptoms associated with pollen, animal allergens, dust mites, and mold/fungi,^15,16 and SCIT may be effective for the treatment of symptoms associated with cockroach exposure.¹¹ SLIT is approved by the US Food and Drug Administration (FDA) for the treatment of several pollen allergens with efficacy rates similar to those of SCIT and with no significant difference in adverse events (AEs).^8,15,16 Direct comparison studies of SCIT and SLIT preparations for treating grass allergy, while of low quality, showed comparable reductions in allergic rhinoconjunctival symptoms.¹⁵

Asthma. AIT (SCIT and SLIT) has been shown to be effective and safe in patients with mild-to-moderate asthma associated with inhalant allergens. Asthma should be controlled prior to initiation of AIT.^6,8,10 Well-known allergic triggers for asthma exacerbation include indoor inhaled allergens (eg, house dust mite, animal dander, cockroach), outdoor inhalant allergens (plants, pollen), and occupational inhaled allergens (silkworm, weevil).^11,13

In one meta-analysis of 796 patients with asthma from 19 different randomized controlled trials, SCIT significantly decreased asthma-related symptom scores (SMD = -0.94; 95% CI, -1.58 to -0.29; P = .004), as well as asthma medication scores (SMD = -1.06; 95% CI, -1.70 to -0.42; P = .001).¹⁸ While AIT has not been shown to improve lung function, meta-analyses have shown that adults with asthma treated with AIT experience fewer/less severe exacerbations and use less rescue medication when compared with those taking placebo.^19,20 Furthermore, studies have shown that SCIT and SLIT reduce asthma symptoms and asthma medication use compared with placebo or usual care in the pediatric population.²⁰

Adults with asthma treated with allergy immunotherapy use less rescue medication when compared to those taking placebo.

As helpful as AIT can be for some patients with mild-to-moderate asthma, patients with severe asthma experience more severe adverse reactions with AIT.²¹ Therefore, most experts recommend against administering AIT to patients with severe asthma.^6,8,21

Continue to: Stinging insects

Stinging insects. VIT is used for patients with hypersensitivity to the venom from insects of the order Hymenoptera (see previous list of insects).^3,11,22 A meta-analysis concluded, based on limited evidence from low-quality studies, that VIT has the potential to substantially reduce the incidence of severe allergic reactions in patients with Hymenoptera sensitivity with 72% of patients benefitting from VIT (number needed to treat [NNT] = 1.4).²² VIT reduces the risk of a systemic reaction, as well as the size and duration of large local reactions (LLRs).^6,22 Immunotherapy for stinging insects also has been shown to improve disease-specific quality of life (risk difference = 1.41 strongly favoring VIT).^6,22

Insect allergens. Research has shown AIT to be an effective therapy for many allergens even though the potency and effectiveness for some allergens are not standardized or regulated.^6,7,11,14 For example, AIT is available for some inhaled insect allergens; however, because the extracts are not standardized, AIT produces inconsistent outcomes.^11,14 As another example, certain occupations lead to exposure to inhaled insect allergens such as silkworm and weevils. AIT is not indicated for either because available silkworm extracts are used only for allergy testing.¹¹ There are no extracts to test for or treat weevil allergy.¹¹

Food. IgE-mediated food allergy can result in oral allergy syndrome, angioedema, urticaria, and/or anaphylaxis.^2,7,8 There is some evidence that AIT raises the threshold of reactivity in children with IgE-mediated food allergies.^6,7,23-25 But the studies available for meta-analyses (some of which involved OIT) were deemed to be of low quality due to a high risk of bias and a small number of participants.^24,25 AIT for food allergies is associated with a substantially increased incidence of moderate adverse reactions, including upper respiratory, gastrointestinal, and skin symptoms, with a probability of 46% during the buildup phase and a number needed to harm (NNH) of 2.1 (95% CI, 1.8-2.5; P < .0001).^6,25 Therefore, experts consider AIT in any form for food hypersensitivity to be investigational.^6,10

Allergen immunotherapy for allergic rhinitis has proven to be effective at improving quality of life and symptom control and decreasing comorbid disease and use of rescue medication.

But preliminary data from a recent phase 3 trial of OIT for peanut allergy involving 499 children and teens are promising; 67.2% tolerated the food challenge of ≥ 600 mg of peanut protein at the completion of peanut OIT without dose-limiting symptoms (difference = 63.2 percentage points; 95% CI, 53-73.3; P < .001).²⁶ More than twice as many participants in the placebo group vs the treatment group experienced AEs that were moderate (59% vs 25%, respectively) or severe (11% vs 5%, respectively).

There are ongoing trials of SCIT, SLIT, and OIT using modified food allergens to make participants less allergic while maintaining immunogenicity.^2,27 Additional trials include adjunctive treatments like probiotics to create safer, more effective options for children with food allergies.^2,27 Keep in mind that children with food allergies often have concomitant allergies (eg, inhalant allergies) that can benefit from AIT.

Continue to: Other clinical practice strategies include...

Other clinical practice strategies include the introduction of extensively heated (baked) milk and egg products, which benefit the majority of milk- and egg-allergic children.^2,28 An American Academy of Allergy, Asthma and Immunology (AAAAI)-sponsored Task Force and the European Academy of Allergy and Clinical Immunology (EAACI) support exclusive breastfeeding for the first 4 to 6 months of life to decrease the risk of developing food allergies.^6,7

Atopic dermatitis (AD). AD is an IgE-mediated skin disease that affects children and adults. AD is associated with asthma, AR, and food allergy.¹³ Early studies showed that AIT reduced topical corticosteroid use and improved the SCORAD (SCORing Atopic Dermatitis; see www.scorad.corti.li/) score.¹⁰ However, Cochrane reviews of studies involving children and adults with AD undergoing AIT via SCIT, SLIT, or OIT routes found that AIT was not effective in treating AD when accounting for the quality and heterogeneity of the studies.^12,29 In addition, there were no significant differences in SCORAD scores.^10,12

Contact allergens. Contact allergens, including plant resins (eg, poison ivy) and metals (eg, nickel) cause local dermatitis through a cell-mediated, delayed hypersensitivity response. AIT is not indicated for contact dermatitis.^6,9

Why use AIT?

First, AIT has been shown to modify disease. Second, because of its disease-modifying properties, AIT may provide cost savings over standard drug treatment in patients with asthma and AR.^17,20,30 In fact, individual studies have demonstrated ≥ 80% cost savings of AIT over standard drug regimens, although meta-analyses have been unable to demonstrate the same.^30,31

In addition, initial studies suggested that AIT might help to prevent the development of new allergen sensitizations.³² One meta-analysis found that AIT decreased the short-term risk of developing asthma in children with AR; however, subsequent studies showed that AIT did not have efficacy in preventing new allergic disease.^31,33

Continue to: How do you administer AIT?

FPs may be asked to administer AIT to their patients. Patients will typically have weekly office visits during the induction phase of AIT and should have appointments every 6 to 12 months during the maintenance phase.^6,8

While allergy immunotherapy has not been shown to improve lung function in patients with asthma, studies have shown that patients experience fewer exacerbations.

Collaboration with an allergy specialist is wise for dosing schedules and possibly for information regarding adverse reactions during administration. It is essential that AIT be administered by clinicians who are knowledgeable about the signs and symptoms of minor allergic reactions (eg, pruritus, mild erythema, and swelling at the administration site) and severe ones (eg, angioedema, shock, anaphylaxis), as well as who have immediate access to emergency medications and resuscitation, should it be needed.^6-8,34

Most (86%) adverse reactions will occur within 30 minutes of administration of AIT; hence, the recommendation is to observe patients for 30 minutes following AIT administration.^6,7,34 Continual training and “mock” severe reaction responses are beneficial for staff administering AIT to ensure appropriate equipment is available and that appropriate procedures are followed. Late-phase reactions can occur and usually present within 6 to 12 hours of administration; thus, it is essential for patients to be educated on the signs and symptoms of adverse reactions and on symptomatic and emergent treatment.^9,34

Experts consider allergy immunotherapy in any form for food hypersensitivity to be investigational.

Rush immunotherapy regimens for inhalant allergens are associated with increased AEs; therefore, pretreatment with antihistamines, leukotriene antagonists, the monoclonal antibody omalizumab, corticosteroids, or combinations of these agents is often used.^6,34 In contrast to inhaled allergens, rush VIT has not been associated with an increased risk of adverse reactions in meta-analyses.^6,22,34 Most experts recommend that AIT be discontinued if anaphylaxis occurs.^8,34

Is AIT safe?

AIT is a proven safe and effective disease-modifying treatment option.^6-8,31,35 Even when AIT is initiated within the season of increased allergen exposure, meta-analyses reveal no increase in adverse events in patients undergoing AIT.³⁵ Given the lack of high-quality evidence confirming the safety of AIT in the following specific situations, both the AAAAI and EAACI have concluded that these conditions/situations are absolute contraindications for AIT due to the risk of severe reactions by activation of underlying disease^8,21,36:

• severe asthma;
• acquired immune deficiency syndrome (AIDS); and
• initiation of AIT during pregnancy.

Continue to: Patients with a history of transplantation...

Patients with a history of transplantation, cancer in remission, human immunodeficiency virus (HIV) without AIDS, and cardiovascular disease have been safely treated with AIT with a < 1.5% incidence of serious adverse events.^6,21,36 It is possible to give patients taking beta-blockers and/or angiotensin converting enzyme inhibitors (ACEIs) AIT with appropriate consideration. Both classes of drugs can interfere with emergency treatment, so one should consider substitution with an agent from another class if possible during AIT.^6,8,20,34 Patients taking ACEIs receiving VIT had substantially increased adverse reactions compared with other forms of AIT; thus, individual risks and benefits must be weighed carefully before initiating VIT.^6,34

Looking ahead

Studies evaluating the indications for AIT in oral allergy syndrome, food allergy, latex allergy, AD, and venom allergy are ongoing.^2,7,10,26 Although the incidence of severe adverse allergy reactions during AIT is rare, there are investigations of using various immune-modifying agents to improve the safety and efficacy of AIT.³⁷ Application of allergen preparation using skin patches, intralymphatic injections, and chemically modified allergens to make them less immunologically reactive are being researched to further improve safety profiles and make AIT less time consuming.³⁸ In Europe and the United States, there is a call for more rigid studies using standardized SLIT preparations. This will allow for an increased number of AIT studies with decreased heterogeneity.

CORRESPONDENCE
Dellyse Bright, MD, Carolinas Medical Center Family Medicine Residency Program, Atrium Health, 2001 Vail Avenue, Suite 400B, Charlotte, NC 28207; Dellyse.Bright@atriumhealth.org.

The prevalence of allergic disease in the general population is quite high; 8.3% of adults and children have asthma and 11.4% of children have skin allergies.¹ Food allergies are present in 8% of children and 5% of adults,² and up to 10% of anaphylactic reactions in the United States are due to stinging insects.³

Allergy immunotherapy has been shown to produce a 2.7- to 13.7-fold overall improvement in hypersensitivity reactions.

Moderate-to-severe food and environmental allergies can negatively affect multiple organ systems and significantly impact morbidity and mortality.⁴ Quality of life and the financial well-being of patients with allergic diseases, as well as that of their families, can also be significantly impacted by these conditions.^4,5 High prevalence and burden of disease mandate that family physicians (FPs) stay up-to-date on the full array of treatment options for allergic diseases. What follows are 6 common questions about allergy immunotherapy (AIT) and the evidence-based answers that will help you to identify and treat appropriate candidates, as well as educate them along the way.

IMAGE: © ALICIA BUELOW

Who is a candidate for AIT?

Patients with moderate-to-severe immunoglobulin (Ig)E-mediated allergies whose symptoms are not adequately controlled by medications and allergen trigger avoidance are candidates for AIT.^6-8 Skin prick/puncture testing provides the most reliable and cost-effective confirmation of allergies that are suspected, based on patient history and clinical assessment for allergic symptoms.⁹ Life-threatening reactions to skin prick/puncture testing are rare.⁹ While in vitro (laboratory) testing for IgE levels to specific antigens may be more convenient for patients and less invasive than skin prick/puncture testing, it is also less sensitive and less reliable at quantifying the severity of sensitization.⁹

What constitutes AIT?

AIT is a disease-modifying treatment that, along with allergen avoidance, can provide long-term remission of allergic disease in certain circumstances.^6,7 Consistent gradual exposure to an allergen helps to dampen the inflammatory reaction driven by T cells and B cells, producing clinical tolerance or desensitization that persists after the discontinuation of AIT.⁸ While subcutaneous immunotherapy (SCIT) is the most widely known type of AIT (ie, allergy shots), there are additional ways that AIT can be administered. These include sublingual immunotherapy (SLIT), venom immunotherapy (VIT), and oral immunotherapy (OIT). The selection of the route of administration depends on the exact nature and symptoms of the allergic condition being treated (TABLE^6,8-12).

AIT involves 2 phases

The first phase is the induction or buildup phase during which patients are given gradually increasing amounts of allergen to induce a protective immunologic response.⁶ After 8 to 28 weeks, the maintenance phase begins, during which continued, consistent allergen exposure is designed to prevent relapse of, and facilitate continued remission of, allergy symptoms.⁶ The maintenance phase of AIT can last 24 to 48 months.^6,10 Certain patients may qualify for an expedited AIT regimen called cluster or rush immunotherapy.⁶

While lab testing may be more convenient for patients and less invasive than skin prick/ puncture testing, it is also less sensitive and less reliable at quantifying the severity of sensitization.

Conventional schedules for AIT involve increasing the dose of allergen given at each visit (1-3 doses/wk), whereas rush dosing involves multiple, increasing doses given in a single extended visit to reach therapeutic desensitization faster.⁶ AIT has been shown to produce a 2.7- to 13.7-fold overall improvement in hypersensitivity reactions.¹⁰

Length of therapy must be individualized

Experts recommend that the length of treatment with AIT be customized for each patient based on the severity of pretreatment allergy symptoms, the benefit experienced with AIT, the inconvenience of AIT to the patient, and the anticipated impact of symptom relapse.^6,10 There are no physiologic symptoms or objective tests that predict which patients will remain in remission after discontinuing AIT; thus, a joint task force of allergy experts suggests that the decision to restart AIT in patients who have a relapse in allergic symptoms should be made based on the same factors used to determine the duration of the maintenance phase.⁶

Continue to: These allergans are appropriate for AIT

Allergens may be described in terms of mechanism and chronicity of exposure. While avoidance of offending allergens is recommended for those who are sensitized, avoidance is not always possible.^6,7,9,13 AIT has been studied as a therapeutic modality to prevent exposure-related symptoms associated with each of the following types of allergens.^6,7,9,11,14

Inhalant allergens circulate in disturbed and undisturbed air and may be seasonal (eg, pollen), perennial (eg, cat/dog allergens), and/or occupational.⁹ They can derive from the indoors (eg, cockroach, cat, dog, dust mite) or outdoors (eg, tree, grass, or weed pollen ),^6,7,9,11 and serve as triggers for many allergic diseases such as allergic rhinitis (AR), allergic rhinoconjunctivitis, allergic dermatitis, and asthma.^7,13

Food allergens. Sensitization to food allergens may produce a range of symptoms.^6,7 One person may experience nothing more than tingling of the lips when eating a peach, while another may experience throat tightness and anaphylaxis due to the aroma of shellfish cooking.

Occupational allergens. Exposure to occupational allergens varies depending on the setting. Those who work in health care or with animals can be exposed to allergens (eg, latex and animal proteins, respectively) that can cause skin or respiratory hypersensitivity reactions. Occupational allergens can also include chemicals; workers in agriculture or housekeeping may be particularly at risk.

Insect allergens. Envenomation by stinging insects of the order Hymenoptera (bees, yellow jackets, hornets, wasps, fire ants) most commonly causes a pruritic, painful local reaction, but patients sensitized to Hymenoptera venom experience systemic allergic reactions that range from mild to life-threatening.^3,6,7

Continue to: When should you use AIT?

Allergic rhinitis (AR). AR can be triggered by exposure to indoor or outdoor inhalant allergens. Research has shown AIT to be an effective treatment for AR and the conjunctivitis caused by inhaled environmental allergens.^15-17 AIT results in improved symptom control and decreased use of rescue medication (standardized mean difference [SMD] -0.32; 95% confidence interval [CI], -0.23 to -0.33, favoring AIT intervention) in patients with seasonal or perennial AR.^15-17

SCIT effectiveness has been demonstrated in sensitized patients who have symptoms associated with pollen, animal allergens, dust mites, and mold/fungi,^15,16 and SCIT may be effective for the treatment of symptoms associated with cockroach exposure.¹¹ SLIT is approved by the US Food and Drug Administration (FDA) for the treatment of several pollen allergens with efficacy rates similar to those of SCIT and with no significant difference in adverse events (AEs).^8,15,16 Direct comparison studies of SCIT and SLIT preparations for treating grass allergy, while of low quality, showed comparable reductions in allergic rhinoconjunctival symptoms.¹⁵

Asthma. AIT (SCIT and SLIT) has been shown to be effective and safe in patients with mild-to-moderate asthma associated with inhalant allergens. Asthma should be controlled prior to initiation of AIT.^6,8,10 Well-known allergic triggers for asthma exacerbation include indoor inhaled allergens (eg, house dust mite, animal dander, cockroach), outdoor inhalant allergens (plants, pollen), and occupational inhaled allergens (silkworm, weevil).^11,13

In one meta-analysis of 796 patients with asthma from 19 different randomized controlled trials, SCIT significantly decreased asthma-related symptom scores (SMD = -0.94; 95% CI, -1.58 to -0.29; P = .004), as well as asthma medication scores (SMD = -1.06; 95% CI, -1.70 to -0.42; P = .001).¹⁸ While AIT has not been shown to improve lung function, meta-analyses have shown that adults with asthma treated with AIT experience fewer/less severe exacerbations and use less rescue medication when compared with those taking placebo.^19,20 Furthermore, studies have shown that SCIT and SLIT reduce asthma symptoms and asthma medication use compared with placebo or usual care in the pediatric population.²⁰

Adults with asthma treated with allergy immunotherapy use less rescue medication when compared to those taking placebo.

As helpful as AIT can be for some patients with mild-to-moderate asthma, patients with severe asthma experience more severe adverse reactions with AIT.²¹ Therefore, most experts recommend against administering AIT to patients with severe asthma.^6,8,21

Continue to: Stinging insects

Stinging insects. VIT is used for patients with hypersensitivity to the venom from insects of the order Hymenoptera (see previous list of insects).^3,11,22 A meta-analysis concluded, based on limited evidence from low-quality studies, that VIT has the potential to substantially reduce the incidence of severe allergic reactions in patients with Hymenoptera sensitivity with 72% of patients benefitting from VIT (number needed to treat [NNT] = 1.4).²² VIT reduces the risk of a systemic reaction, as well as the size and duration of large local reactions (LLRs).^6,22 Immunotherapy for stinging insects also has been shown to improve disease-specific quality of life (risk difference = 1.41 strongly favoring VIT).^6,22

Insect allergens. Research has shown AIT to be an effective therapy for many allergens even though the potency and effectiveness for some allergens are not standardized or regulated.^6,7,11,14 For example, AIT is available for some inhaled insect allergens; however, because the extracts are not standardized, AIT produces inconsistent outcomes.^11,14 As another example, certain occupations lead to exposure to inhaled insect allergens such as silkworm and weevils. AIT is not indicated for either because available silkworm extracts are used only for allergy testing.¹¹ There are no extracts to test for or treat weevil allergy.¹¹

Food. IgE-mediated food allergy can result in oral allergy syndrome, angioedema, urticaria, and/or anaphylaxis.^2,7,8 There is some evidence that AIT raises the threshold of reactivity in children with IgE-mediated food allergies.^6,7,23-25 But the studies available for meta-analyses (some of which involved OIT) were deemed to be of low quality due to a high risk of bias and a small number of participants.^24,25 AIT for food allergies is associated with a substantially increased incidence of moderate adverse reactions, including upper respiratory, gastrointestinal, and skin symptoms, with a probability of 46% during the buildup phase and a number needed to harm (NNH) of 2.1 (95% CI, 1.8-2.5; P < .0001).^6,25 Therefore, experts consider AIT in any form for food hypersensitivity to be investigational.^6,10

Allergen immunotherapy for allergic rhinitis has proven to be effective at improving quality of life and symptom control and decreasing comorbid disease and use of rescue medication.

But preliminary data from a recent phase 3 trial of OIT for peanut allergy involving 499 children and teens are promising; 67.2% tolerated the food challenge of ≥ 600 mg of peanut protein at the completion of peanut OIT without dose-limiting symptoms (difference = 63.2 percentage points; 95% CI, 53-73.3; P < .001).²⁶ More than twice as many participants in the placebo group vs the treatment group experienced AEs that were moderate (59% vs 25%, respectively) or severe (11% vs 5%, respectively).

There are ongoing trials of SCIT, SLIT, and OIT using modified food allergens to make participants less allergic while maintaining immunogenicity.^2,27 Additional trials include adjunctive treatments like probiotics to create safer, more effective options for children with food allergies.^2,27 Keep in mind that children with food allergies often have concomitant allergies (eg, inhalant allergies) that can benefit from AIT.

Continue to: Other clinical practice strategies include...

Other clinical practice strategies include the introduction of extensively heated (baked) milk and egg products, which benefit the majority of milk- and egg-allergic children.^2,28 An American Academy of Allergy, Asthma and Immunology (AAAAI)-sponsored Task Force and the European Academy of Allergy and Clinical Immunology (EAACI) support exclusive breastfeeding for the first 4 to 6 months of life to decrease the risk of developing food allergies.^6,7

Atopic dermatitis (AD). AD is an IgE-mediated skin disease that affects children and adults. AD is associated with asthma, AR, and food allergy.¹³ Early studies showed that AIT reduced topical corticosteroid use and improved the SCORAD (SCORing Atopic Dermatitis; see www.scorad.corti.li/) score.¹⁰ However, Cochrane reviews of studies involving children and adults with AD undergoing AIT via SCIT, SLIT, or OIT routes found that AIT was not effective in treating AD when accounting for the quality and heterogeneity of the studies.^12,29 In addition, there were no significant differences in SCORAD scores.^10,12

Contact allergens. Contact allergens, including plant resins (eg, poison ivy) and metals (eg, nickel) cause local dermatitis through a cell-mediated, delayed hypersensitivity response. AIT is not indicated for contact dermatitis.^6,9

Why use AIT?

First, AIT has been shown to modify disease. Second, because of its disease-modifying properties, AIT may provide cost savings over standard drug treatment in patients with asthma and AR.^17,20,30 In fact, individual studies have demonstrated ≥ 80% cost savings of AIT over standard drug regimens, although meta-analyses have been unable to demonstrate the same.^30,31

In addition, initial studies suggested that AIT might help to prevent the development of new allergen sensitizations.³² One meta-analysis found that AIT decreased the short-term risk of developing asthma in children with AR; however, subsequent studies showed that AIT did not have efficacy in preventing new allergic disease.^31,33

Continue to: How do you administer AIT?

FPs may be asked to administer AIT to their patients. Patients will typically have weekly office visits during the induction phase of AIT and should have appointments every 6 to 12 months during the maintenance phase.^6,8

While allergy immunotherapy has not been shown to improve lung function in patients with asthma, studies have shown that patients experience fewer exacerbations.

Collaboration with an allergy specialist is wise for dosing schedules and possibly for information regarding adverse reactions during administration. It is essential that AIT be administered by clinicians who are knowledgeable about the signs and symptoms of minor allergic reactions (eg, pruritus, mild erythema, and swelling at the administration site) and severe ones (eg, angioedema, shock, anaphylaxis), as well as who have immediate access to emergency medications and resuscitation, should it be needed.^6-8,34

Most (86%) adverse reactions will occur within 30 minutes of administration of AIT; hence, the recommendation is to observe patients for 30 minutes following AIT administration.^6,7,34 Continual training and “mock” severe reaction responses are beneficial for staff administering AIT to ensure appropriate equipment is available and that appropriate procedures are followed. Late-phase reactions can occur and usually present within 6 to 12 hours of administration; thus, it is essential for patients to be educated on the signs and symptoms of adverse reactions and on symptomatic and emergent treatment.^9,34

Experts consider allergy immunotherapy in any form for food hypersensitivity to be investigational.

Rush immunotherapy regimens for inhalant allergens are associated with increased AEs; therefore, pretreatment with antihistamines, leukotriene antagonists, the monoclonal antibody omalizumab, corticosteroids, or combinations of these agents is often used.^6,34 In contrast to inhaled allergens, rush VIT has not been associated with an increased risk of adverse reactions in meta-analyses.^6,22,34 Most experts recommend that AIT be discontinued if anaphylaxis occurs.^8,34

Is AIT safe?

AIT is a proven safe and effective disease-modifying treatment option.^6-8,31,35 Even when AIT is initiated within the season of increased allergen exposure, meta-analyses reveal no increase in adverse events in patients undergoing AIT.³⁵ Given the lack of high-quality evidence confirming the safety of AIT in the following specific situations, both the AAAAI and EAACI have concluded that these conditions/situations are absolute contraindications for AIT due to the risk of severe reactions by activation of underlying disease^8,21,36:

• severe asthma;
• acquired immune deficiency syndrome (AIDS); and
• initiation of AIT during pregnancy.

Continue to: Patients with a history of transplantation...

Patients with a history of transplantation, cancer in remission, human immunodeficiency virus (HIV) without AIDS, and cardiovascular disease have been safely treated with AIT with a < 1.5% incidence of serious adverse events.^6,21,36 It is possible to give patients taking beta-blockers and/or angiotensin converting enzyme inhibitors (ACEIs) AIT with appropriate consideration. Both classes of drugs can interfere with emergency treatment, so one should consider substitution with an agent from another class if possible during AIT.^6,8,20,34 Patients taking ACEIs receiving VIT had substantially increased adverse reactions compared with other forms of AIT; thus, individual risks and benefits must be weighed carefully before initiating VIT.^6,34

Looking ahead

Studies evaluating the indications for AIT in oral allergy syndrome, food allergy, latex allergy, AD, and venom allergy are ongoing.^2,7,10,26 Although the incidence of severe adverse allergy reactions during AIT is rare, there are investigations of using various immune-modifying agents to improve the safety and efficacy of AIT.³⁷ Application of allergen preparation using skin patches, intralymphatic injections, and chemically modified allergens to make them less immunologically reactive are being researched to further improve safety profiles and make AIT less time consuming.³⁸ In Europe and the United States, there is a call for more rigid studies using standardized SLIT preparations. This will allow for an increased number of AIT studies with decreased heterogeneity.

CORRESPONDENCE
Dellyse Bright, MD, Carolinas Medical Center Family Medicine Residency Program, Atrium Health, 2001 Vail Avenue, Suite 400B, Charlotte, NC 28207; Dellyse.Bright@atriumhealth.org.

The FP recognized this as classic pyoderma gangrenosum (PG)—a challenging condition to treat and not within the typical scope of practice for an FP. Nonhealing, well-defined leg ulcers in a person with Crohn's disease (or any type of inflammatory bowel disease) are often seen with PG. Pathergy—the development of an exaggerated injury following minor trauma—is known to occur with PG.

The FP also noted the violet-blue coloration around the borders of the ulcers, which is referred to as a “gun-metal border.” He considered doing a biopsy on the edge of the ulcer to rule out other conditions and to see if there was a neutrophilic infiltrate that is typically seen with PG. However, the FP realized that pathergy could be stimulated by a biopsy, so he decided to refer the patient to Dermatology.

Knowing that the patient might have to wait a few months to see a dermatologist, the FP consulted online sources and prescribed topical clobetasol ointment to be applied twice daily as an initial therapy. This was not successful, so after a phone consult with the dermatologist, the FP added oral prednisone 40 mg/d for the next 2 weeks until the dermatologist could see the patient.

‌

Photos and text for Photo Rounds Friday courtesy of Richard P. Usatine, MD. This case was adapted from: Mayeaux, EJ, Usatine R. Pyoderma gangrenosum. In: Usatine R, Smith M, Mayeaux EJ, et al. Color Atlas and Synopsis of Family Medicine. 3rd ed. New York, NY: McGraw-Hill; 2019:1147-1152.

To learn more about the newest 3rd edition of the Color Atlas and Synopsis of Family Medicine, see: https://www.amazon.com/Color-Atlas-Synopsis-Family-Medicine/dp/1259862046/

You can get the Color Atlas of Family Medicine app by clicking on this link: usatinemedia.com

The FP recognized this as classic pyoderma gangrenosum (PG)—a challenging condition to treat and not within the typical scope of practice for an FP. Nonhealing, well-defined leg ulcers in a person with Crohn's disease (or any type of inflammatory bowel disease) are often seen with PG. Pathergy—the development of an exaggerated injury following minor trauma—is known to occur with PG.

The FP also noted the violet-blue coloration around the borders of the ulcers, which is referred to as a “gun-metal border.” He considered doing a biopsy on the edge of the ulcer to rule out other conditions and to see if there was a neutrophilic infiltrate that is typically seen with PG. However, the FP realized that pathergy could be stimulated by a biopsy, so he decided to refer the patient to Dermatology.

Knowing that the patient might have to wait a few months to see a dermatologist, the FP consulted online sources and prescribed topical clobetasol ointment to be applied twice daily as an initial therapy. This was not successful, so after a phone consult with the dermatologist, the FP added oral prednisone 40 mg/d for the next 2 weeks until the dermatologist could see the patient.

‌

Photos and text for Photo Rounds Friday courtesy of Richard P. Usatine, MD. This case was adapted from: Mayeaux, EJ, Usatine R. Pyoderma gangrenosum. In: Usatine R, Smith M, Mayeaux EJ, et al. Color Atlas and Synopsis of Family Medicine. 3rd ed. New York, NY: McGraw-Hill; 2019:1147-1152.

To learn more about the newest 3rd edition of the Color Atlas and Synopsis of Family Medicine, see: https://www.amazon.com/Color-Atlas-Synopsis-Family-Medicine/dp/1259862046/

You can get the Color Atlas of Family Medicine app by clicking on this link: usatinemedia.com

The FP recognized this as classic pyoderma gangrenosum (PG)—a challenging condition to treat and not within the typical scope of practice for an FP. Nonhealing, well-defined leg ulcers in a person with Crohn's disease (or any type of inflammatory bowel disease) are often seen with PG. Pathergy—the development of an exaggerated injury following minor trauma—is known to occur with PG.

The FP also noted the violet-blue coloration around the borders of the ulcers, which is referred to as a “gun-metal border.” He considered doing a biopsy on the edge of the ulcer to rule out other conditions and to see if there was a neutrophilic infiltrate that is typically seen with PG. However, the FP realized that pathergy could be stimulated by a biopsy, so he decided to refer the patient to Dermatology.

Knowing that the patient might have to wait a few months to see a dermatologist, the FP consulted online sources and prescribed topical clobetasol ointment to be applied twice daily as an initial therapy. This was not successful, so after a phone consult with the dermatologist, the FP added oral prednisone 40 mg/d for the next 2 weeks until the dermatologist could see the patient.

‌

Photos and text for Photo Rounds Friday courtesy of Richard P. Usatine, MD. This case was adapted from: Mayeaux, EJ, Usatine R. Pyoderma gangrenosum. In: Usatine R, Smith M, Mayeaux EJ, et al. Color Atlas and Synopsis of Family Medicine. 3rd ed. New York, NY: McGraw-Hill; 2019:1147-1152.

To learn more about the newest 3rd edition of the Color Atlas and Synopsis of Family Medicine, see: https://www.amazon.com/Color-Atlas-Synopsis-Family-Medicine/dp/1259862046/

You can get the Color Atlas of Family Medicine app by clicking on this link: usatinemedia.com

Reference

Johnson Jones ML, Chapin-Bardales J, Bizune D. Extragenital chlamydia and gonorrhea among community venue –  attending men who have sex with men – Five cities, United States, 2017. MMWR Morb Mortal Wkly Rep. 2019;68:321-325. https://www.cdc.gov/mmwr/volumes/68/wr/mm6814a1.htm?s_cid=mm6814a1_w. Accessed May 23, 2019.

Reference

Johnson Jones ML, Chapin-Bardales J, Bizune D. Extragenital chlamydia and gonorrhea among community venue –  attending men who have sex with men – Five cities, United States, 2017. MMWR Morb Mortal Wkly Rep. 2019;68:321-325. https://www.cdc.gov/mmwr/volumes/68/wr/mm6814a1.htm?s_cid=mm6814a1_w. Accessed May 23, 2019.

Reference

Johnson Jones ML, Chapin-Bardales J, Bizune D. Extragenital chlamydia and gonorrhea among community venue –  attending men who have sex with men – Five cities, United States, 2017. MMWR Morb Mortal Wkly Rep. 2019;68:321-325. https://www.cdc.gov/mmwr/volumes/68/wr/mm6814a1.htm?s_cid=mm6814a1_w. Accessed May 23, 2019.

At the hospital, the physicians noted that there were no lesions on the mucous membranes of the patient’s eyes, ears, nose, mouth or anus and his vital signs were within normal limits. He was empirically treated with 1 dose of methylprednisolone (125 mg intravenous [IV]) and started on IV piperacillin-tazobactam and vancomycin. The patient subsequently revealed that he’d had a similar experience a year earlier after being treated with TMP-SMX for cellulitis. During the previous episode, he said the lesions were located on the exact same areas of his glans penis and chin. Based on the morphologic characteristics of the eruption and the history of similar lesions that appeared following previous treatment with TMP-SMX, the physician diagnosed disseminated fixed-drug eruption in this patient.

A fixed-drug eruption is an adverse cutaneous reaction to a drug that is defined by a dusky red or violaceous macule, which evolves into a patch, and eventually, an edematous plaque. Fixed-drug eruptions are typically solitary, but may be generalized (as was the case with this patient). The pathophysiology of the disease involves resident intra-epidermal CD8+ T-cells resembling effector memory T-cells. These T-cells are increased in number at the dermoepidermal junction of normal appearing skin; their aberrant activation leads to an inflammatory response, stimulating tissue destruction and formation of the classic fixed-drug lesion.

This diagnosis usually is made based on a history of similar lesions recurring at the same location in response to a specific drug and the classic physical exam findings of well-demarcated, edematous, and violaceous plaques. A skin biopsy may be performed to confirm a fixed-drug eruption in the case of clinical equipoise.

Fixed-drug eruptions occasionally exhibit bullae and erosions and must be differentiated from more serious generalized bullous diseases, including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). The differential diagnosis also includes erythema multiforme, early bullous drug eruption, and bullous arthropod assault, which may leave similar hyperpigmented patches.

Management of a disseminated fixed-drug eruption requires a thorough history to identify the causative agent (including over-the-counter drugs, herbals, topicals, and eye drops). Most patients are asymptomatic, but some (like this patient) are symptomatic and experience generalized pruritus, cutaneous burning, and/or pain. Symptomatic therapy includes oral antihistamines and potent topical glucocorticoid ointment for non-eroded lesions. Additionally, if not medically contraindicated, oral steroids may be used for generalized or extremely painful mucosal lesions at a dose of 0.5 mg/kg daily for 3 to 5 days.

Local wound care of eroded lesions includes keeping the site moist with a bland emollient and bandaging. The inciting agent must be added to the patient’s allergy list and avoided in the future. In equivocal cases, it is prudent to admit the patient for observation to ensure that the eruption is not a nascent SJS or TEN eruption.

In this case, the patient was admitted to the observation unit overnight to monitor for the appearance of systemic symptoms and to assess the evolution of the rash for further mucosal involvement that could have indicated SJS. Upon reassessment the next day, his older lesions had evolved into vesiculated and necrotic areas as per the natural history of severe fixed-drug eruption. He was prescribed prednisone 40 mg/d for 3 days to help with local inflammation, pain, and itching. TMP-SMX was added to his allergy list and he was given local wound care instructions. He was told to return if he developed any systemic symptoms.

‌

This case was adapted from: Bucher J, Rahnama-Moghadam S, Osswald S. Generalized rash follows ankle ulceration. J Fam Pract. 2016;65:489-491.

At the hospital, the physicians noted that there were no lesions on the mucous membranes of the patient’s eyes, ears, nose, mouth or anus and his vital signs were within normal limits. He was empirically treated with 1 dose of methylprednisolone (125 mg intravenous [IV]) and started on IV piperacillin-tazobactam and vancomycin. The patient subsequently revealed that he’d had a similar experience a year earlier after being treated with TMP-SMX for cellulitis. During the previous episode, he said the lesions were located on the exact same areas of his glans penis and chin. Based on the morphologic characteristics of the eruption and the history of similar lesions that appeared following previous treatment with TMP-SMX, the physician diagnosed disseminated fixed-drug eruption in this patient.

A fixed-drug eruption is an adverse cutaneous reaction to a drug that is defined by a dusky red or violaceous macule, which evolves into a patch, and eventually, an edematous plaque. Fixed-drug eruptions are typically solitary, but may be generalized (as was the case with this patient). The pathophysiology of the disease involves resident intra-epidermal CD8+ T-cells resembling effector memory T-cells. These T-cells are increased in number at the dermoepidermal junction of normal appearing skin; their aberrant activation leads to an inflammatory response, stimulating tissue destruction and formation of the classic fixed-drug lesion.

This diagnosis usually is made based on a history of similar lesions recurring at the same location in response to a specific drug and the classic physical exam findings of well-demarcated, edematous, and violaceous plaques. A skin biopsy may be performed to confirm a fixed-drug eruption in the case of clinical equipoise.

Fixed-drug eruptions occasionally exhibit bullae and erosions and must be differentiated from more serious generalized bullous diseases, including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). The differential diagnosis also includes erythema multiforme, early bullous drug eruption, and bullous arthropod assault, which may leave similar hyperpigmented patches.

Management of a disseminated fixed-drug eruption requires a thorough history to identify the causative agent (including over-the-counter drugs, herbals, topicals, and eye drops). Most patients are asymptomatic, but some (like this patient) are symptomatic and experience generalized pruritus, cutaneous burning, and/or pain. Symptomatic therapy includes oral antihistamines and potent topical glucocorticoid ointment for non-eroded lesions. Additionally, if not medically contraindicated, oral steroids may be used for generalized or extremely painful mucosal lesions at a dose of 0.5 mg/kg daily for 3 to 5 days.

Local wound care of eroded lesions includes keeping the site moist with a bland emollient and bandaging. The inciting agent must be added to the patient’s allergy list and avoided in the future. In equivocal cases, it is prudent to admit the patient for observation to ensure that the eruption is not a nascent SJS or TEN eruption.

In this case, the patient was admitted to the observation unit overnight to monitor for the appearance of systemic symptoms and to assess the evolution of the rash for further mucosal involvement that could have indicated SJS. Upon reassessment the next day, his older lesions had evolved into vesiculated and necrotic areas as per the natural history of severe fixed-drug eruption. He was prescribed prednisone 40 mg/d for 3 days to help with local inflammation, pain, and itching. TMP-SMX was added to his allergy list and he was given local wound care instructions. He was told to return if he developed any systemic symptoms.

‌

This case was adapted from: Bucher J, Rahnama-Moghadam S, Osswald S. Generalized rash follows ankle ulceration. J Fam Pract. 2016;65:489-491.

At the hospital, the physicians noted that there were no lesions on the mucous membranes of the patient’s eyes, ears, nose, mouth or anus and his vital signs were within normal limits. He was empirically treated with 1 dose of methylprednisolone (125 mg intravenous [IV]) and started on IV piperacillin-tazobactam and vancomycin. The patient subsequently revealed that he’d had a similar experience a year earlier after being treated with TMP-SMX for cellulitis. During the previous episode, he said the lesions were located on the exact same areas of his glans penis and chin. Based on the morphologic characteristics of the eruption and the history of similar lesions that appeared following previous treatment with TMP-SMX, the physician diagnosed disseminated fixed-drug eruption in this patient.

A fixed-drug eruption is an adverse cutaneous reaction to a drug that is defined by a dusky red or violaceous macule, which evolves into a patch, and eventually, an edematous plaque. Fixed-drug eruptions are typically solitary, but may be generalized (as was the case with this patient). The pathophysiology of the disease involves resident intra-epidermal CD8+ T-cells resembling effector memory T-cells. These T-cells are increased in number at the dermoepidermal junction of normal appearing skin; their aberrant activation leads to an inflammatory response, stimulating tissue destruction and formation of the classic fixed-drug lesion.

This diagnosis usually is made based on a history of similar lesions recurring at the same location in response to a specific drug and the classic physical exam findings of well-demarcated, edematous, and violaceous plaques. A skin biopsy may be performed to confirm a fixed-drug eruption in the case of clinical equipoise.

Fixed-drug eruptions occasionally exhibit bullae and erosions and must be differentiated from more serious generalized bullous diseases, including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). The differential diagnosis also includes erythema multiforme, early bullous drug eruption, and bullous arthropod assault, which may leave similar hyperpigmented patches.

Management of a disseminated fixed-drug eruption requires a thorough history to identify the causative agent (including over-the-counter drugs, herbals, topicals, and eye drops). Most patients are asymptomatic, but some (like this patient) are symptomatic and experience generalized pruritus, cutaneous burning, and/or pain. Symptomatic therapy includes oral antihistamines and potent topical glucocorticoid ointment for non-eroded lesions. Additionally, if not medically contraindicated, oral steroids may be used for generalized or extremely painful mucosal lesions at a dose of 0.5 mg/kg daily for 3 to 5 days.

Local wound care of eroded lesions includes keeping the site moist with a bland emollient and bandaging. The inciting agent must be added to the patient’s allergy list and avoided in the future. In equivocal cases, it is prudent to admit the patient for observation to ensure that the eruption is not a nascent SJS or TEN eruption.

In this case, the patient was admitted to the observation unit overnight to monitor for the appearance of systemic symptoms and to assess the evolution of the rash for further mucosal involvement that could have indicated SJS. Upon reassessment the next day, his older lesions had evolved into vesiculated and necrotic areas as per the natural history of severe fixed-drug eruption. He was prescribed prednisone 40 mg/d for 3 days to help with local inflammation, pain, and itching. TMP-SMX was added to his allergy list and he was given local wound care instructions. He was told to return if he developed any systemic symptoms.

‌

This case was adapted from: Bucher J, Rahnama-Moghadam S, Osswald S. Generalized rash follows ankle ulceration. J Fam Pract. 2016;65:489-491.

The FP thought this looked like granuloma annulare (GA) but had never seen so many lesions on a patient. Some lesions were not round (more oval or elongated), while others were not completely enclosed geometric shapes (with breaks in the multiple ring patterns). However, all of the lesions were slightly raised with erythema and no scale. (The FP also considered tinea corporis, but ruled it out because there was no scale.)

He consulted some Internet resources and was convinced that this was disseminated GA. The greatest risk factor for this somewhat mysterious disease of unknown origin is female gender. It is also often associated with diabetes, but diabetes is not the cause.

Although intralesional steroids work when treating disseminated GA, this approach is not realistic for widespread disease. A number of options have been studied and reported in small series or case reports. The FP presented various options to the patient, and together they decided to try pentoxifylline 400 mg 3 times daily for systemic treatment. Pentoxifylline is approved for claudication and has few adverse effects or risks. While this treatment is off-label for GA, there are no FDA approved treatments.

During a follow-up visit 1 month later, the number of lesions had been reduced by half. The FP continued treating the patient with pentoxifylline with the hope of achieving full resolution.

‌

Photos and text for Photo Rounds Friday courtesy of Richard P. Usatine, MD. This case was adapted from: Mauskar M, Usatine R. Granuloma annulare. In: Usatine R, Smith M, Mayeaux EJ, et al. Color Atlas and Synopsis of Family Medicine. 3rd ed. New York, NY: McGraw-Hill; 2019:1141-1146.

To learn more about the newest 3rd edition of the Color Atlas and Synopsis of Family Medicine, see: https://www.amazon.com/Color-Atlas-Synopsis-Family-Medicine/dp/1259862046/

You can get the Color Atlas of Family Medicine app by clicking on this link: usatinemedia.com

The FP thought this looked like granuloma annulare (GA) but had never seen so many lesions on a patient. Some lesions were not round (more oval or elongated), while others were not completely enclosed geometric shapes (with breaks in the multiple ring patterns). However, all of the lesions were slightly raised with erythema and no scale. (The FP also considered tinea corporis, but ruled it out because there was no scale.)

He consulted some Internet resources and was convinced that this was disseminated GA. The greatest risk factor for this somewhat mysterious disease of unknown origin is female gender. It is also often associated with diabetes, but diabetes is not the cause.

Although intralesional steroids work when treating disseminated GA, this approach is not realistic for widespread disease. A number of options have been studied and reported in small series or case reports. The FP presented various options to the patient, and together they decided to try pentoxifylline 400 mg 3 times daily for systemic treatment. Pentoxifylline is approved for claudication and has few adverse effects or risks. While this treatment is off-label for GA, there are no FDA approved treatments.

During a follow-up visit 1 month later, the number of lesions had been reduced by half. The FP continued treating the patient with pentoxifylline with the hope of achieving full resolution.

‌

Photos and text for Photo Rounds Friday courtesy of Richard P. Usatine, MD. This case was adapted from: Mauskar M, Usatine R. Granuloma annulare. In: Usatine R, Smith M, Mayeaux EJ, et al. Color Atlas and Synopsis of Family Medicine. 3rd ed. New York, NY: McGraw-Hill; 2019:1141-1146.

To learn more about the newest 3rd edition of the Color Atlas and Synopsis of Family Medicine, see: https://www.amazon.com/Color-Atlas-Synopsis-Family-Medicine/dp/1259862046/

You can get the Color Atlas of Family Medicine app by clicking on this link: usatinemedia.com

The FP thought this looked like granuloma annulare (GA) but had never seen so many lesions on a patient. Some lesions were not round (more oval or elongated), while others were not completely enclosed geometric shapes (with breaks in the multiple ring patterns). However, all of the lesions were slightly raised with erythema and no scale. (The FP also considered tinea corporis, but ruled it out because there was no scale.)

He consulted some Internet resources and was convinced that this was disseminated GA. The greatest risk factor for this somewhat mysterious disease of unknown origin is female gender. It is also often associated with diabetes, but diabetes is not the cause.

Although intralesional steroids work when treating disseminated GA, this approach is not realistic for widespread disease. A number of options have been studied and reported in small series or case reports. The FP presented various options to the patient, and together they decided to try pentoxifylline 400 mg 3 times daily for systemic treatment. Pentoxifylline is approved for claudication and has few adverse effects or risks. While this treatment is off-label for GA, there are no FDA approved treatments.

During a follow-up visit 1 month later, the number of lesions had been reduced by half. The FP continued treating the patient with pentoxifylline with the hope of achieving full resolution.

‌

Photos and text for Photo Rounds Friday courtesy of Richard P. Usatine, MD. This case was adapted from: Mauskar M, Usatine R. Granuloma annulare. In: Usatine R, Smith M, Mayeaux EJ, et al. Color Atlas and Synopsis of Family Medicine. 3rd ed. New York, NY: McGraw-Hill; 2019:1141-1146.

To learn more about the newest 3rd edition of the Color Atlas and Synopsis of Family Medicine, see: https://www.amazon.com/Color-Atlas-Synopsis-Family-Medicine/dp/1259862046/

You can get the Color Atlas of Family Medicine app by clicking on this link: usatinemedia.com

The FP diagnosed granuloma annulare (GA) in this patient, based on the typical clinical appearance of a raised ring on the back of the hand with no scale.

GA is a common benign cutaneous, inflammatory disorder of unknown origin. It affects twice as many women as men. It features annular lesions that have raised borders and are skin-colored to erythematous. The rings may become hyperpigmented and often feature a central depression. These lesions are typically 1 to 5 cm wide. Although the classical appearance of GA is annular, the rings may not always be complete. Most importantly, there is no scaling, which one would expect to see in tinea infections, also known as “ringworm.”

The most common form of granuloma annulare is localized, as it was in this case. It typically presents on the dorsal surfaces of extremities, especially of the hands and feet. When the presentation is classic, there is no need for a biopsy to confirm the diagnosis.

The most effective treatment for local disease is intralesional triamcinolone (5mg/mL). (See Watch & Learn: Intralesional injections.) The FP offered this treatment to the patient, and she tolerated the procedure well. The GA resolved over the weeks that followed with some faint hypopigmentation that lasted for several months. The patient was happy with the results.

‌

Photos and text for Photo Rounds Friday courtesy of Richard P. Usatine, MD. This case was adapted from: Mauskar M, Usatine R. Granuloma annulare. In: Usatine R, Smith M, Mayeaux EJ, et al. Color Atlas and Synopsis of Family Medicine. 3rd ed. New York, NY: McGraw-Hill; 2019:1141-1146.

To learn more about the newest 3rd edition of the Color Atlas and Synopsis of Family Medicine, see: https://www.amazon.com/Color-Atlas-Synopsis-Family-Medicine/dp/1259862046/

You can get the Color Atlas of Family Medicine app by clicking on this link: usatinemedia.com

The FP diagnosed granuloma annulare (GA) in this patient, based on the typical clinical appearance of a raised ring on the back of the hand with no scale.

GA is a common benign cutaneous, inflammatory disorder of unknown origin. It affects twice as many women as men. It features annular lesions that have raised borders and are skin-colored to erythematous. The rings may become hyperpigmented and often feature a central depression. These lesions are typically 1 to 5 cm wide. Although the classical appearance of GA is annular, the rings may not always be complete. Most importantly, there is no scaling, which one would expect to see in tinea infections, also known as “ringworm.”

The most common form of granuloma annulare is localized, as it was in this case. It typically presents on the dorsal surfaces of extremities, especially of the hands and feet. When the presentation is classic, there is no need for a biopsy to confirm the diagnosis.

The most effective treatment for local disease is intralesional triamcinolone (5mg/mL). (See Watch & Learn: Intralesional injections.) The FP offered this treatment to the patient, and she tolerated the procedure well. The GA resolved over the weeks that followed with some faint hypopigmentation that lasted for several months. The patient was happy with the results.

‌

Photos and text for Photo Rounds Friday courtesy of Richard P. Usatine, MD. This case was adapted from: Mauskar M, Usatine R. Granuloma annulare. In: Usatine R, Smith M, Mayeaux EJ, et al. Color Atlas and Synopsis of Family Medicine. 3rd ed. New York, NY: McGraw-Hill; 2019:1141-1146.

To learn more about the newest 3rd edition of the Color Atlas and Synopsis of Family Medicine, see: https://www.amazon.com/Color-Atlas-Synopsis-Family-Medicine/dp/1259862046/

You can get the Color Atlas of Family Medicine app by clicking on this link: usatinemedia.com

The FP diagnosed granuloma annulare (GA) in this patient, based on the typical clinical appearance of a raised ring on the back of the hand with no scale.

GA is a common benign cutaneous, inflammatory disorder of unknown origin. It affects twice as many women as men. It features annular lesions that have raised borders and are skin-colored to erythematous. The rings may become hyperpigmented and often feature a central depression. These lesions are typically 1 to 5 cm wide. Although the classical appearance of GA is annular, the rings may not always be complete. Most importantly, there is no scaling, which one would expect to see in tinea infections, also known as “ringworm.”

The most common form of granuloma annulare is localized, as it was in this case. It typically presents on the dorsal surfaces of extremities, especially of the hands and feet. When the presentation is classic, there is no need for a biopsy to confirm the diagnosis.

The most effective treatment for local disease is intralesional triamcinolone (5mg/mL). (See Watch & Learn: Intralesional injections.) The FP offered this treatment to the patient, and she tolerated the procedure well. The GA resolved over the weeks that followed with some faint hypopigmentation that lasted for several months. The patient was happy with the results.

‌

Photos and text for Photo Rounds Friday courtesy of Richard P. Usatine, MD. This case was adapted from: Mauskar M, Usatine R. Granuloma annulare. In: Usatine R, Smith M, Mayeaux EJ, et al. Color Atlas and Synopsis of Family Medicine. 3rd ed. New York, NY: McGraw-Hill; 2019:1141-1146.

To learn more about the newest 3rd edition of the Color Atlas and Synopsis of Family Medicine, see: https://www.amazon.com/Color-Atlas-Synopsis-Family-Medicine/dp/1259862046/

You can get the Color Atlas of Family Medicine app by clicking on this link: usatinemedia.com

The differential diagnosis included psoriasis, drug eruption, and a cutaneous T-cell lymphoma.

A drug eruption could have been due to an over-the-counter medication or supplement, so the lack of improvement from stopping the antihypertensive medication did not rule out this diagnosis. Psoriasis does not always show erythema in persons of color, but these plaques were not typical of psoriasis. (There also were some flat patches that were even less typical of psoriasis.)

The FP performed a 4-mm punch biopsy on one of the hyperpigmented plaques on the abdomen. A 4-mm punch biopsy is generally an ideal method for determining the cause of an unknown skin rash, and it is usually better to choose a lesion on the upper body rather than below the waist if the rash is widespread. (See the Watch & Learn video on “Punch biopsy.”)

The FP also prescribed a 1-pound tub of 0.1% triamcinolone ointment for symptomatic relief as this could help any of the possible diagnoses being considered. The pathology report came back as mycosis fungoides, the most common type of cutaneous T-cell lymphoma.

The patient was sent to Hematology/Oncology for further evaluation and treatment. Mycosis fungoides can have both patches and plaques and frequently involves the trunk more than the extremities (which was the situation in this case). It is important to consider uncommon diagnoses like this in the differential when the initial diagnosis does not appear to be responding to treatment or there is something atypical about the presentation of an expected diagnosis.

‌

Photos and text for Photo Rounds Friday courtesy of Richard P. Usatine, MD. This case was adapted from: Chacon G, Nayar A, Usatine R, Smith M. Cutaneous T-cell lymphoma. In: Usatine R, Smith M, Mayeaux EJ, et al. Color Atlas and Synopsis of Family Medicine. 3rd ed. New York, NY: McGraw-Hill; 2019:1124-1131.

To learn more about the newest 3rd edition of the Color Atlas and Synopsis of Family Medicine, see: https://www.amazon.com/Color-Atlas-Synopsis-Family-Medicine/dp/1259862046/

You can get the Color Atlas of Family Medicine app by clicking on this link: usatinemedia.com

The differential diagnosis included psoriasis, drug eruption, and a cutaneous T-cell lymphoma.

A drug eruption could have been due to an over-the-counter medication or supplement, so the lack of improvement from stopping the antihypertensive medication did not rule out this diagnosis. Psoriasis does not always show erythema in persons of color, but these plaques were not typical of psoriasis. (There also were some flat patches that were even less typical of psoriasis.)

The FP performed a 4-mm punch biopsy on one of the hyperpigmented plaques on the abdomen. A 4-mm punch biopsy is generally an ideal method for determining the cause of an unknown skin rash, and it is usually better to choose a lesion on the upper body rather than below the waist if the rash is widespread. (See the Watch & Learn video on “Punch biopsy.”)

The FP also prescribed a 1-pound tub of 0.1% triamcinolone ointment for symptomatic relief as this could help any of the possible diagnoses being considered. The pathology report came back as mycosis fungoides, the most common type of cutaneous T-cell lymphoma.

The patient was sent to Hematology/Oncology for further evaluation and treatment. Mycosis fungoides can have both patches and plaques and frequently involves the trunk more than the extremities (which was the situation in this case). It is important to consider uncommon diagnoses like this in the differential when the initial diagnosis does not appear to be responding to treatment or there is something atypical about the presentation of an expected diagnosis.

‌

Photos and text for Photo Rounds Friday courtesy of Richard P. Usatine, MD. This case was adapted from: Chacon G, Nayar A, Usatine R, Smith M. Cutaneous T-cell lymphoma. In: Usatine R, Smith M, Mayeaux EJ, et al. Color Atlas and Synopsis of Family Medicine. 3rd ed. New York, NY: McGraw-Hill; 2019:1124-1131.

To learn more about the newest 3rd edition of the Color Atlas and Synopsis of Family Medicine, see: https://www.amazon.com/Color-Atlas-Synopsis-Family-Medicine/dp/1259862046/

You can get the Color Atlas of Family Medicine app by clicking on this link: usatinemedia.com

The differential diagnosis included psoriasis, drug eruption, and a cutaneous T-cell lymphoma.

A drug eruption could have been due to an over-the-counter medication or supplement, so the lack of improvement from stopping the antihypertensive medication did not rule out this diagnosis. Psoriasis does not always show erythema in persons of color, but these plaques were not typical of psoriasis. (There also were some flat patches that were even less typical of psoriasis.)

The FP performed a 4-mm punch biopsy on one of the hyperpigmented plaques on the abdomen. A 4-mm punch biopsy is generally an ideal method for determining the cause of an unknown skin rash, and it is usually better to choose a lesion on the upper body rather than below the waist if the rash is widespread. (See the Watch & Learn video on “Punch biopsy.”)

The FP also prescribed a 1-pound tub of 0.1% triamcinolone ointment for symptomatic relief as this could help any of the possible diagnoses being considered. The pathology report came back as mycosis fungoides, the most common type of cutaneous T-cell lymphoma.

The patient was sent to Hematology/Oncology for further evaluation and treatment. Mycosis fungoides can have both patches and plaques and frequently involves the trunk more than the extremities (which was the situation in this case). It is important to consider uncommon diagnoses like this in the differential when the initial diagnosis does not appear to be responding to treatment or there is something atypical about the presentation of an expected diagnosis.

‌

Photos and text for Photo Rounds Friday courtesy of Richard P. Usatine, MD. This case was adapted from: Chacon G, Nayar A, Usatine R, Smith M. Cutaneous T-cell lymphoma. In: Usatine R, Smith M, Mayeaux EJ, et al. Color Atlas and Synopsis of Family Medicine. 3rd ed. New York, NY: McGraw-Hill; 2019:1124-1131.

To learn more about the newest 3rd edition of the Color Atlas and Synopsis of Family Medicine, see: https://www.amazon.com/Color-Atlas-Synopsis-Family-Medicine/dp/1259862046/

You can get the Color Atlas of Family Medicine app by clicking on this link: usatinemedia.com

Since the measles outbreak in the Pacific Northwest (where I did my training and remain in touch with colleagues and patients), parents with infants ages 6 to 11 months are requesting vaccinations before 12 months—the standard age to start immunizations.¹ But physicians decline to provide inoculation, citing institutional policy on the risks of early vaccination. What are these risks, and how should we respond when parents ask about early vaccination?

The safety and efficacy of early vaccination are well documented. Early vaccination is a technique employed to curb outbreaks both in the United States and worldwide. Guidelines from the Centers for Disease Control and Prevention (CDC) recommend vaccinating infants at 6 months of age if they will be traveling,² and the World Health Organization (WHO) recommends vaccinations during a measles outbreak as part of intensified service delivery or in settings, such as daycare facilities, in which there is an increased risk for disease exposure during an outbreak.³ Any dose given before 12 months is considered supplemental, and the child must still complete the regular 2-dose vaccine schedule. Studies on the adverse effect profiles of vaccines show that the younger the infant, the fewer adverse events occur—because adverse events reflect the increasingly robust immune response that comes with age.⁴

Many physicians are concerned about adequate immune response. In vaccine research, this is gauged by the proportion of patients with seroconversion after vaccination. This is also reflected in vaccine efficacy (VE), which gradually increases with age and maturity of the immune system. For example, measles VE is 60% to 70% in 6-to-8-month cohorts⁵ and 70% to 80% in 9-to-11-month cohorts.⁶ VE at 12 months is in the 90% range, and completion of the 2-dose series yields a VE of ≥ 95%.⁷ Thus, while the vaccine is more effective at later ages, it still provides protection to younger cohorts.

Early vaccination has few risks and significant benefit. Therefore, relaxing the lower boundary for the measles vaccine is appropriate.

“Blunting” (ie, a reduced immune response to the second dose of vaccine³) is another concern with early measles vaccination, but a WHO meta-analysis proved this concern to be unfounded.^1,3 Twelve papers examining seropositivity in children who received a second measles vaccine after early primary vaccination found a pooled proportion of seropositivity of 97%.^1,8,9 Furthermore, evidence shows that children have sustained measles-specific T-cell responses after early primary measles immunization.¹⁰

Early vaccination has few risks and significant benefit. Therefore, in light of the recent measles outbreak, relaxing the lower boundary for the measles vaccine is appropriate. In addition to physically protecting the patient and general population, honoring parents’ requests for vaccination respects their autonomy and fosters trust. Synthesis of good science with a trusting doctor–patient relationship is key to ending the measles outbreak.

Rachel Roth, MD
Tel Aviv, Israel

Since the measles outbreak in the Pacific Northwest (where I did my training and remain in touch with colleagues and patients), parents with infants ages 6 to 11 months are requesting vaccinations before 12 months—the standard age to start immunizations.¹ But physicians decline to provide inoculation, citing institutional policy on the risks of early vaccination. What are these risks, and how should we respond when parents ask about early vaccination?

The safety and efficacy of early vaccination are well documented. Early vaccination is a technique employed to curb outbreaks both in the United States and worldwide. Guidelines from the Centers for Disease Control and Prevention (CDC) recommend vaccinating infants at 6 months of age if they will be traveling,² and the World Health Organization (WHO) recommends vaccinations during a measles outbreak as part of intensified service delivery or in settings, such as daycare facilities, in which there is an increased risk for disease exposure during an outbreak.³ Any dose given before 12 months is considered supplemental, and the child must still complete the regular 2-dose vaccine schedule. Studies on the adverse effect profiles of vaccines show that the younger the infant, the fewer adverse events occur—because adverse events reflect the increasingly robust immune response that comes with age.⁴

Many physicians are concerned about adequate immune response. In vaccine research, this is gauged by the proportion of patients with seroconversion after vaccination. This is also reflected in vaccine efficacy (VE), which gradually increases with age and maturity of the immune system. For example, measles VE is 60% to 70% in 6-to-8-month cohorts⁵ and 70% to 80% in 9-to-11-month cohorts.⁶ VE at 12 months is in the 90% range, and completion of the 2-dose series yields a VE of ≥ 95%.⁷ Thus, while the vaccine is more effective at later ages, it still provides protection to younger cohorts.

Early vaccination has few risks and significant benefit. Therefore, relaxing the lower boundary for the measles vaccine is appropriate.

“Blunting” (ie, a reduced immune response to the second dose of vaccine³) is another concern with early measles vaccination, but a WHO meta-analysis proved this concern to be unfounded.^1,3 Twelve papers examining seropositivity in children who received a second measles vaccine after early primary vaccination found a pooled proportion of seropositivity of 97%.^1,8,9 Furthermore, evidence shows that children have sustained measles-specific T-cell responses after early primary measles immunization.¹⁰

Early vaccination has few risks and significant benefit. Therefore, in light of the recent measles outbreak, relaxing the lower boundary for the measles vaccine is appropriate. In addition to physically protecting the patient and general population, honoring parents’ requests for vaccination respects their autonomy and fosters trust. Synthesis of good science with a trusting doctor–patient relationship is key to ending the measles outbreak.

Rachel Roth, MD
Tel Aviv, Israel

Since the measles outbreak in the Pacific Northwest (where I did my training and remain in touch with colleagues and patients), parents with infants ages 6 to 11 months are requesting vaccinations before 12 months—the standard age to start immunizations.¹ But physicians decline to provide inoculation, citing institutional policy on the risks of early vaccination. What are these risks, and how should we respond when parents ask about early vaccination?

The safety and efficacy of early vaccination are well documented. Early vaccination is a technique employed to curb outbreaks both in the United States and worldwide. Guidelines from the Centers for Disease Control and Prevention (CDC) recommend vaccinating infants at 6 months of age if they will be traveling,² and the World Health Organization (WHO) recommends vaccinations during a measles outbreak as part of intensified service delivery or in settings, such as daycare facilities, in which there is an increased risk for disease exposure during an outbreak.³ Any dose given before 12 months is considered supplemental, and the child must still complete the regular 2-dose vaccine schedule. Studies on the adverse effect profiles of vaccines show that the younger the infant, the fewer adverse events occur—because adverse events reflect the increasingly robust immune response that comes with age.⁴

Many physicians are concerned about adequate immune response. In vaccine research, this is gauged by the proportion of patients with seroconversion after vaccination. This is also reflected in vaccine efficacy (VE), which gradually increases with age and maturity of the immune system. For example, measles VE is 60% to 70% in 6-to-8-month cohorts⁵ and 70% to 80% in 9-to-11-month cohorts.⁶ VE at 12 months is in the 90% range, and completion of the 2-dose series yields a VE of ≥ 95%.⁷ Thus, while the vaccine is more effective at later ages, it still provides protection to younger cohorts.

Early vaccination has few risks and significant benefit. Therefore, relaxing the lower boundary for the measles vaccine is appropriate.

“Blunting” (ie, a reduced immune response to the second dose of vaccine³) is another concern with early measles vaccination, but a WHO meta-analysis proved this concern to be unfounded.^1,3 Twelve papers examining seropositivity in children who received a second measles vaccine after early primary vaccination found a pooled proportion of seropositivity of 97%.^1,8,9 Furthermore, evidence shows that children have sustained measles-specific T-cell responses after early primary measles immunization.¹⁰

Early vaccination has few risks and significant benefit. Therefore, in light of the recent measles outbreak, relaxing the lower boundary for the measles vaccine is appropriate. In addition to physically protecting the patient and general population, honoring parents’ requests for vaccination respects their autonomy and fosters trust. Synthesis of good science with a trusting doctor–patient relationship is key to ending the measles outbreak.

Rachel Roth, MD
Tel Aviv, Israel

The average life expectancy in the United States declined from 78.9 years in 2014 to 78.6 years in 2017.¹ The 2017 figure—78.6 years—means life expectancy is shorter in the United States than in other countries.¹ The decline is due, in part, to the drug overdose epidemic in the United States.² In 2017, 70,237 people died by drug overdose²—with prescription drugs, heroin, and opioids (especially fentanyl) being the major threats.³ From 2016 to 2017, overdoses from synthetic opioids, such as fentanyl, fentanyl analogs, and tramadol, increased from 6.2 to 9 per 100,000 people.²

The decline in life expectancy is due, in part, to the drug overdose epidemic in the United States.

These statistics should motivate all health care professionals to improve the general public’s health metrics, especially when treating patients with substance use disorders. But to best do so, we need a collaborative effort across many professions—not just health care providers, but also public health officials, elected government leaders, and law enforcement. To better define what this would entail, we suggest ways in which these groups could expand their roles to help reduce overdose deaths.

Health care professionals:

• implement safer opioid prescribing for patients who have chronic pain;
• educate patients about the risks of opioid use;
• consider alternative therapies for pain management; and
• utilize electronic databases to monitor controlled substance prescribing.

Public health officials:

• expand naloxone distribution; and
• enhance harm reduction (eg, syringe exchange programs, substance abuse treatment options).

Government leaders:

• draft legislation that allows the use of better interventions for treating individuals with drug dependence or those who overdose; and
• improve criminal justice approaches so that laws are less punitive and more therapeutic for individuals who suffer from drug dependence.

Law enforcement:

• supply naltrexone kits to first responders and provide appropriate training.

Kuldeep Ghosh, MD, MS
Rajashekhar Yeruva, MD
Steven Lippmann, MD
Louisville, Ky

The average life expectancy in the United States declined from 78.9 years in 2014 to 78.6 years in 2017.¹ The 2017 figure—78.6 years—means life expectancy is shorter in the United States than in other countries.¹ The decline is due, in part, to the drug overdose epidemic in the United States.² In 2017, 70,237 people died by drug overdose²—with prescription drugs, heroin, and opioids (especially fentanyl) being the major threats.³ From 2016 to 2017, overdoses from synthetic opioids, such as fentanyl, fentanyl analogs, and tramadol, increased from 6.2 to 9 per 100,000 people.²

The decline in life expectancy is due, in part, to the drug overdose epidemic in the United States.

These statistics should motivate all health care professionals to improve the general public’s health metrics, especially when treating patients with substance use disorders. But to best do so, we need a collaborative effort across many professions—not just health care providers, but also public health officials, elected government leaders, and law enforcement. To better define what this would entail, we suggest ways in which these groups could expand their roles to help reduce overdose deaths.

Health care professionals:

• implement safer opioid prescribing for patients who have chronic pain;
• educate patients about the risks of opioid use;
• consider alternative therapies for pain management; and
• utilize electronic databases to monitor controlled substance prescribing.

Public health officials:

• expand naloxone distribution; and
• enhance harm reduction (eg, syringe exchange programs, substance abuse treatment options).

Government leaders:

• draft legislation that allows the use of better interventions for treating individuals with drug dependence or those who overdose; and
• improve criminal justice approaches so that laws are less punitive and more therapeutic for individuals who suffer from drug dependence.

Law enforcement:

• supply naltrexone kits to first responders and provide appropriate training.

Kuldeep Ghosh, MD, MS
Rajashekhar Yeruva, MD
Steven Lippmann, MD
Louisville, Ky

The average life expectancy in the United States declined from 78.9 years in 2014 to 78.6 years in 2017.¹ The 2017 figure—78.6 years—means life expectancy is shorter in the United States than in other countries.¹ The decline is due, in part, to the drug overdose epidemic in the United States.² In 2017, 70,237 people died by drug overdose²—with prescription drugs, heroin, and opioids (especially fentanyl) being the major threats.³ From 2016 to 2017, overdoses from synthetic opioids, such as fentanyl, fentanyl analogs, and tramadol, increased from 6.2 to 9 per 100,000 people.²

The decline in life expectancy is due, in part, to the drug overdose epidemic in the United States.

These statistics should motivate all health care professionals to improve the general public’s health metrics, especially when treating patients with substance use disorders. But to best do so, we need a collaborative effort across many professions—not just health care providers, but also public health officials, elected government leaders, and law enforcement. To better define what this would entail, we suggest ways in which these groups could expand their roles to help reduce overdose deaths.

Health care professionals:

• implement safer opioid prescribing for patients who have chronic pain;
• educate patients about the risks of opioid use;
• consider alternative therapies for pain management; and
• utilize electronic databases to monitor controlled substance prescribing.

Public health officials:

• expand naloxone distribution; and
• enhance harm reduction (eg, syringe exchange programs, substance abuse treatment options).

Government leaders:

• draft legislation that allows the use of better interventions for treating individuals with drug dependence or those who overdose; and
• improve criminal justice approaches so that laws are less punitive and more therapeutic for individuals who suffer from drug dependence.

Law enforcement:

• supply naltrexone kits to first responders and provide appropriate training.

Kuldeep Ghosh, MD, MS
Rajashekhar Yeruva, MD
Steven Lippmann, MD
Louisville, Ky