Case Reports

Irreducible ankle fracture-dislocation secondary to tibialis posterior tendon interposition is a rare but documented complication most commonly associated with Lauge-Hansen classification pronation–external rotation ankle fractures.^1-4 Entrapment of the tibialis posterior tendon has been documented in the syndesmosis (tibiotalar joint)^1,2,4 and within a medial malleolus fracture.5 To our knowledge, however, there are no case reports of entrapment of the tibialis posterior tendon in a posterior malleolus fracture.

Ankle arthroscopy performed at time of fracture fixation is gaining in popularity because of its enhanced ability to document and treat intra-articular pathology associated with the initial injury.^6,7 In addition, percutaneous fixation of a posterior malleolar fragment with arthroscopic assessment of the articular surface reduction may be valuable, as evaluation of tibial plafond fracture reduction by plain radiographs and fluoroscopy has proved to have limitations.^8,9

In this article, we present the case of a patient who underwent attempted arthroscopy-assisted reduction of the posterior malleolus with entrapment of the tibialis posterior tendon within the posterior malleolar fracture fragment. The tendon was irreducible with arthroscopic techniques, necessitating posteromedial incision and subsequent open reduction of the incarcerated structure. The patient provided written informed consent for print and electronic publication of this case report.

Case Report

A 67-year-old man slipped and fell on ice while jogging and subsequently presented to the emergency department with a closed bimalleolar ankle fracture-dislocation. Plain radiography (Figure 1) and computed tomography (CT) showed an oblique lateral malleolar fracture and a large posterior malleolar fracture. Further examination of the CT scan revealed entrapment of the tibialis posterior tendon within the posterior malleolar fracture (Figure 2).

Two days after injury, the patient was taken to the operating room for ankle arthroscopy with planned extrication of the entrapped tibialis posterior tendon and possible arthroscopy-assisted percutaneous fixation of the posterior malleolar fracture and open fixation of the distal fibula fracture. Diagnostic arthroscopy revealed a deltoid ligament injury (Figure 3) and a loose piece of articular cartilage (~1 cm in diameter), which was excised. No donor site for this cartilage fragment was identified with further arthroscopic evaluation. During arthroscopic examination, the tibialis posterior tendon was visualized within the joint, incarcerated within the posterior malleolar fracture (Figure 4). Attempts to release the tibialis posterior tendon from the fracture site using arthroscopic instruments and closed reduction techniques were unsuccessful, both with and without noninvasive skeletal traction applied to the ankle.

After multiple unsuccessful attempts to extract the tibialis posterior tendon arthroscopically, traction was removed, and a separate incision was made over the posteromedial aspect of the ankle. The tibialis posterior tendon was identified within the fracture site and was removed using an angled clamp (Figure 5). The fracture was reduced and held provisionally with a large tenaculum clamp. Two anterior-to-posterior, partially threaded cannulated screws were placed for fixation after adequate fracture reduction was confirmed on fluoroscopy. As a medial incision was made to extract the tibialis posterior tendon, the joint could not retain arthroscopic fluid, and visualization of the posterior fracture fragment after tendon removal was difficult. Therefore, arthroscopy-assisted reduction could not be completed.

Next, the lateral malleolus was open-reduced, and fixation was achieved using a standard interfragmentary lag screw and a lateral neutralization plate technique (Figure 6). After surgery, the patient was immobilized in a posterior splint with side gussets. Two weeks later, the incisions were healing well, and the tibialis posterior tendon was functioning normally. The sutures were removed, the patient was transitioned to a controlled ankle movement (CAM) boot, and ankle and subtalar range-of-motion exercises were initiated. The patient remained non-weight-bearing for 6 weeks. Radiographs 6 weeks after surgery showed healing fractures with stable hardware (Figure 7). The patient demonstrated 5/5 strength of the tibialis posterior tendon without subluxation or dislocation. There was no tenderness to palpation over the fracture sites or tibialis posterior tendon. The patient began progressive weight-bearing in a CAM boot and physical therapy for range of motion and strengthening.

Discussion

Tibialis posterior tendon injuries—including rupture, dislocation, and entrapment—are well-described complications of ankle injuries.^1,2,5,10 Most commonly, the tibialis posterior tendon has been reported to cause a mechanical block to reduction in lateral subtalar dislocations.^11-13 In addition, there are case reports of isolated traumatic dislocations of the tibialis posterior tendon without rupture, requiring operative stabilization and retinaculum repair with or without deepening of the posterior groove.^14,15

Posterior malleolar ankle fractures remain controversial, with respect to both need for fixation and fixation methods. Although multiple investigators have advocated operative treatment for such fractures that exceed 25% to 33% of the anteroposterior dimension of the tibial plafond, there are no conclusive studies or evidence-based guidelines for treating these fractures.^16,17 Anatomical reduction and plating are important to restore articular congruity and increase syndesmotic stability; recent studies have demonstrated that fixation of posterior malleolar fractures provides more syndesmotic stability than trans-syndesmotic screws do.^18,19 Indirect reduction of the posterior malleolar fragment after fibula fixation is often accepted as adequate. Whether indirect or direct reduction is attempted, close attention should be given to plain radiographs after attempted reduction, and consideration should be given to possible soft-tissue or bony interposition if malreduction is identified.^16,17 Plain radiographs are unreliable in assessing posterior malleolar fragment size as well as amount of comminution and impaction.^8,9 Therefore, an arthroscopy-assisted approach coupled with percutaneous fixation may provide more reliable fracture reduction over indirect fracture reduction with fibular fixation, with less dissection than a formal posterolateral approach with posterior plating.

Not all ankle fractures require CT. However, for posterior malleolus fractures thought to require fixation, preoperative CT may help in determining if percutaneous fixation with or without arthroscopic guidance is a feasible treatment option. Ideally, percutaneous reduction can obviate the need for a larger posterolateral incision and buttress plate and, with arthroscopic assistance, may be superior to indirect reduction with fluoroscopy.

In our patient’s case, arthroscopic assistance facilitated diagnosis of an entrapped structure that would have been difficult to identify, particularly without preoperative CT. It may be difficult to identify imperfect reduction of the posterior malleolus on plain radiographs alone, and arthroscopy-assisted fixation enhances the surgeon’s ability to consider reduction, view incarcerated structures within the joint, and treat articular injuries. We do not routinely use ankle arthroscopy as an adjunct to ankle fracture fixation, but judicious use in select cases can facilitate treatment of intra-articular injuries and facilitate visualization and reduction of posterior malleolar fracture fragments before percutaneous anterior-to-posterior cannulated screw fixation. If an open incision is required, as in the present case, visualization becomes difficult secondary to fluid extravasation. However, we think avoiding the morbidity associated with an open incision is worthwhile for fixation of posterior malleolus fractures.

Conclusion

Close inspection of both preoperative and intraoperative radiographs is required to ensure adequate reduction of a posterior malleolar fragment without soft-tissue or bony interposition in the reduction of ankle fractures. Although not previously reported, posterior tendon entrapment within the posterior malleolus fracture may occur and may require arthroscopic or open techniques to ensure adequate extrication of the tendon to allow for posterior malleolar fracture reduction and fixation. This case report highlights one indication for arthroscopy in the treatment of ankle fractures despite the fact that the tibialis posterior tendon was openly removed. Arthroscopic assistance in acute ankle injuries allows the surgeon to evaluate articular cartilage injuries and ensure there are no interposed structures while checking reduction of the posterior malleolar fracture fragment when present.

Irreducible ankle fracture-dislocation secondary to tibialis posterior tendon interposition is a rare but documented complication most commonly associated with Lauge-Hansen classification pronation–external rotation ankle fractures.^1-4 Entrapment of the tibialis posterior tendon has been documented in the syndesmosis (tibiotalar joint)^1,2,4 and within a medial malleolus fracture.5 To our knowledge, however, there are no case reports of entrapment of the tibialis posterior tendon in a posterior malleolus fracture.

Ankle arthroscopy performed at time of fracture fixation is gaining in popularity because of its enhanced ability to document and treat intra-articular pathology associated with the initial injury.^6,7 In addition, percutaneous fixation of a posterior malleolar fragment with arthroscopic assessment of the articular surface reduction may be valuable, as evaluation of tibial plafond fracture reduction by plain radiographs and fluoroscopy has proved to have limitations.^8,9

In this article, we present the case of a patient who underwent attempted arthroscopy-assisted reduction of the posterior malleolus with entrapment of the tibialis posterior tendon within the posterior malleolar fracture fragment. The tendon was irreducible with arthroscopic techniques, necessitating posteromedial incision and subsequent open reduction of the incarcerated structure. The patient provided written informed consent for print and electronic publication of this case report.

Case Report

A 67-year-old man slipped and fell on ice while jogging and subsequently presented to the emergency department with a closed bimalleolar ankle fracture-dislocation. Plain radiography (Figure 1) and computed tomography (CT) showed an oblique lateral malleolar fracture and a large posterior malleolar fracture. Further examination of the CT scan revealed entrapment of the tibialis posterior tendon within the posterior malleolar fracture (Figure 2).

Two days after injury, the patient was taken to the operating room for ankle arthroscopy with planned extrication of the entrapped tibialis posterior tendon and possible arthroscopy-assisted percutaneous fixation of the posterior malleolar fracture and open fixation of the distal fibula fracture. Diagnostic arthroscopy revealed a deltoid ligament injury (Figure 3) and a loose piece of articular cartilage (~1 cm in diameter), which was excised. No donor site for this cartilage fragment was identified with further arthroscopic evaluation. During arthroscopic examination, the tibialis posterior tendon was visualized within the joint, incarcerated within the posterior malleolar fracture (Figure 4). Attempts to release the tibialis posterior tendon from the fracture site using arthroscopic instruments and closed reduction techniques were unsuccessful, both with and without noninvasive skeletal traction applied to the ankle.

After multiple unsuccessful attempts to extract the tibialis posterior tendon arthroscopically, traction was removed, and a separate incision was made over the posteromedial aspect of the ankle. The tibialis posterior tendon was identified within the fracture site and was removed using an angled clamp (Figure 5). The fracture was reduced and held provisionally with a large tenaculum clamp. Two anterior-to-posterior, partially threaded cannulated screws were placed for fixation after adequate fracture reduction was confirmed on fluoroscopy. As a medial incision was made to extract the tibialis posterior tendon, the joint could not retain arthroscopic fluid, and visualization of the posterior fracture fragment after tendon removal was difficult. Therefore, arthroscopy-assisted reduction could not be completed.

Next, the lateral malleolus was open-reduced, and fixation was achieved using a standard interfragmentary lag screw and a lateral neutralization plate technique (Figure 6). After surgery, the patient was immobilized in a posterior splint with side gussets. Two weeks later, the incisions were healing well, and the tibialis posterior tendon was functioning normally. The sutures were removed, the patient was transitioned to a controlled ankle movement (CAM) boot, and ankle and subtalar range-of-motion exercises were initiated. The patient remained non-weight-bearing for 6 weeks. Radiographs 6 weeks after surgery showed healing fractures with stable hardware (Figure 7). The patient demonstrated 5/5 strength of the tibialis posterior tendon without subluxation or dislocation. There was no tenderness to palpation over the fracture sites or tibialis posterior tendon. The patient began progressive weight-bearing in a CAM boot and physical therapy for range of motion and strengthening.

Discussion

Tibialis posterior tendon injuries—including rupture, dislocation, and entrapment—are well-described complications of ankle injuries.^1,2,5,10 Most commonly, the tibialis posterior tendon has been reported to cause a mechanical block to reduction in lateral subtalar dislocations.^11-13 In addition, there are case reports of isolated traumatic dislocations of the tibialis posterior tendon without rupture, requiring operative stabilization and retinaculum repair with or without deepening of the posterior groove.^14,15

Posterior malleolar ankle fractures remain controversial, with respect to both need for fixation and fixation methods. Although multiple investigators have advocated operative treatment for such fractures that exceed 25% to 33% of the anteroposterior dimension of the tibial plafond, there are no conclusive studies or evidence-based guidelines for treating these fractures.^16,17 Anatomical reduction and plating are important to restore articular congruity and increase syndesmotic stability; recent studies have demonstrated that fixation of posterior malleolar fractures provides more syndesmotic stability than trans-syndesmotic screws do.^18,19 Indirect reduction of the posterior malleolar fragment after fibula fixation is often accepted as adequate. Whether indirect or direct reduction is attempted, close attention should be given to plain radiographs after attempted reduction, and consideration should be given to possible soft-tissue or bony interposition if malreduction is identified.^16,17 Plain radiographs are unreliable in assessing posterior malleolar fragment size as well as amount of comminution and impaction.^8,9 Therefore, an arthroscopy-assisted approach coupled with percutaneous fixation may provide more reliable fracture reduction over indirect fracture reduction with fibular fixation, with less dissection than a formal posterolateral approach with posterior plating.

Not all ankle fractures require CT. However, for posterior malleolus fractures thought to require fixation, preoperative CT may help in determining if percutaneous fixation with or without arthroscopic guidance is a feasible treatment option. Ideally, percutaneous reduction can obviate the need for a larger posterolateral incision and buttress plate and, with arthroscopic assistance, may be superior to indirect reduction with fluoroscopy.

In our patient’s case, arthroscopic assistance facilitated diagnosis of an entrapped structure that would have been difficult to identify, particularly without preoperative CT. It may be difficult to identify imperfect reduction of the posterior malleolus on plain radiographs alone, and arthroscopy-assisted fixation enhances the surgeon’s ability to consider reduction, view incarcerated structures within the joint, and treat articular injuries. We do not routinely use ankle arthroscopy as an adjunct to ankle fracture fixation, but judicious use in select cases can facilitate treatment of intra-articular injuries and facilitate visualization and reduction of posterior malleolar fracture fragments before percutaneous anterior-to-posterior cannulated screw fixation. If an open incision is required, as in the present case, visualization becomes difficult secondary to fluid extravasation. However, we think avoiding the morbidity associated with an open incision is worthwhile for fixation of posterior malleolus fractures.

Conclusion

Close inspection of both preoperative and intraoperative radiographs is required to ensure adequate reduction of a posterior malleolar fragment without soft-tissue or bony interposition in the reduction of ankle fractures. Although not previously reported, posterior tendon entrapment within the posterior malleolus fracture may occur and may require arthroscopic or open techniques to ensure adequate extrication of the tendon to allow for posterior malleolar fracture reduction and fixation. This case report highlights one indication for arthroscopy in the treatment of ankle fractures despite the fact that the tibialis posterior tendon was openly removed. Arthroscopic assistance in acute ankle injuries allows the surgeon to evaluate articular cartilage injuries and ensure there are no interposed structures while checking reduction of the posterior malleolar fracture fragment when present.

Irreducible ankle fracture-dislocation secondary to tibialis posterior tendon interposition is a rare but documented complication most commonly associated with Lauge-Hansen classification pronation–external rotation ankle fractures.^1-4 Entrapment of the tibialis posterior tendon has been documented in the syndesmosis (tibiotalar joint)^1,2,4 and within a medial malleolus fracture.5 To our knowledge, however, there are no case reports of entrapment of the tibialis posterior tendon in a posterior malleolus fracture.

Ankle arthroscopy performed at time of fracture fixation is gaining in popularity because of its enhanced ability to document and treat intra-articular pathology associated with the initial injury.^6,7 In addition, percutaneous fixation of a posterior malleolar fragment with arthroscopic assessment of the articular surface reduction may be valuable, as evaluation of tibial plafond fracture reduction by plain radiographs and fluoroscopy has proved to have limitations.^8,9

In this article, we present the case of a patient who underwent attempted arthroscopy-assisted reduction of the posterior malleolus with entrapment of the tibialis posterior tendon within the posterior malleolar fracture fragment. The tendon was irreducible with arthroscopic techniques, necessitating posteromedial incision and subsequent open reduction of the incarcerated structure. The patient provided written informed consent for print and electronic publication of this case report.

Case Report

A 67-year-old man slipped and fell on ice while jogging and subsequently presented to the emergency department with a closed bimalleolar ankle fracture-dislocation. Plain radiography (Figure 1) and computed tomography (CT) showed an oblique lateral malleolar fracture and a large posterior malleolar fracture. Further examination of the CT scan revealed entrapment of the tibialis posterior tendon within the posterior malleolar fracture (Figure 2).

Two days after injury, the patient was taken to the operating room for ankle arthroscopy with planned extrication of the entrapped tibialis posterior tendon and possible arthroscopy-assisted percutaneous fixation of the posterior malleolar fracture and open fixation of the distal fibula fracture. Diagnostic arthroscopy revealed a deltoid ligament injury (Figure 3) and a loose piece of articular cartilage (~1 cm in diameter), which was excised. No donor site for this cartilage fragment was identified with further arthroscopic evaluation. During arthroscopic examination, the tibialis posterior tendon was visualized within the joint, incarcerated within the posterior malleolar fracture (Figure 4). Attempts to release the tibialis posterior tendon from the fracture site using arthroscopic instruments and closed reduction techniques were unsuccessful, both with and without noninvasive skeletal traction applied to the ankle.

After multiple unsuccessful attempts to extract the tibialis posterior tendon arthroscopically, traction was removed, and a separate incision was made over the posteromedial aspect of the ankle. The tibialis posterior tendon was identified within the fracture site and was removed using an angled clamp (Figure 5). The fracture was reduced and held provisionally with a large tenaculum clamp. Two anterior-to-posterior, partially threaded cannulated screws were placed for fixation after adequate fracture reduction was confirmed on fluoroscopy. As a medial incision was made to extract the tibialis posterior tendon, the joint could not retain arthroscopic fluid, and visualization of the posterior fracture fragment after tendon removal was difficult. Therefore, arthroscopy-assisted reduction could not be completed.

Next, the lateral malleolus was open-reduced, and fixation was achieved using a standard interfragmentary lag screw and a lateral neutralization plate technique (Figure 6). After surgery, the patient was immobilized in a posterior splint with side gussets. Two weeks later, the incisions were healing well, and the tibialis posterior tendon was functioning normally. The sutures were removed, the patient was transitioned to a controlled ankle movement (CAM) boot, and ankle and subtalar range-of-motion exercises were initiated. The patient remained non-weight-bearing for 6 weeks. Radiographs 6 weeks after surgery showed healing fractures with stable hardware (Figure 7). The patient demonstrated 5/5 strength of the tibialis posterior tendon without subluxation or dislocation. There was no tenderness to palpation over the fracture sites or tibialis posterior tendon. The patient began progressive weight-bearing in a CAM boot and physical therapy for range of motion and strengthening.

Discussion

Tibialis posterior tendon injuries—including rupture, dislocation, and entrapment—are well-described complications of ankle injuries.^1,2,5,10 Most commonly, the tibialis posterior tendon has been reported to cause a mechanical block to reduction in lateral subtalar dislocations.^11-13 In addition, there are case reports of isolated traumatic dislocations of the tibialis posterior tendon without rupture, requiring operative stabilization and retinaculum repair with or without deepening of the posterior groove.^14,15

Posterior malleolar ankle fractures remain controversial, with respect to both need for fixation and fixation methods. Although multiple investigators have advocated operative treatment for such fractures that exceed 25% to 33% of the anteroposterior dimension of the tibial plafond, there are no conclusive studies or evidence-based guidelines for treating these fractures.^16,17 Anatomical reduction and plating are important to restore articular congruity and increase syndesmotic stability; recent studies have demonstrated that fixation of posterior malleolar fractures provides more syndesmotic stability than trans-syndesmotic screws do.^18,19 Indirect reduction of the posterior malleolar fragment after fibula fixation is often accepted as adequate. Whether indirect or direct reduction is attempted, close attention should be given to plain radiographs after attempted reduction, and consideration should be given to possible soft-tissue or bony interposition if malreduction is identified.^16,17 Plain radiographs are unreliable in assessing posterior malleolar fragment size as well as amount of comminution and impaction.^8,9 Therefore, an arthroscopy-assisted approach coupled with percutaneous fixation may provide more reliable fracture reduction over indirect fracture reduction with fibular fixation, with less dissection than a formal posterolateral approach with posterior plating.

Not all ankle fractures require CT. However, for posterior malleolus fractures thought to require fixation, preoperative CT may help in determining if percutaneous fixation with or without arthroscopic guidance is a feasible treatment option. Ideally, percutaneous reduction can obviate the need for a larger posterolateral incision and buttress plate and, with arthroscopic assistance, may be superior to indirect reduction with fluoroscopy.

In our patient’s case, arthroscopic assistance facilitated diagnosis of an entrapped structure that would have been difficult to identify, particularly without preoperative CT. It may be difficult to identify imperfect reduction of the posterior malleolus on plain radiographs alone, and arthroscopy-assisted fixation enhances the surgeon’s ability to consider reduction, view incarcerated structures within the joint, and treat articular injuries. We do not routinely use ankle arthroscopy as an adjunct to ankle fracture fixation, but judicious use in select cases can facilitate treatment of intra-articular injuries and facilitate visualization and reduction of posterior malleolar fracture fragments before percutaneous anterior-to-posterior cannulated screw fixation. If an open incision is required, as in the present case, visualization becomes difficult secondary to fluid extravasation. However, we think avoiding the morbidity associated with an open incision is worthwhile for fixation of posterior malleolus fractures.

Conclusion

Close inspection of both preoperative and intraoperative radiographs is required to ensure adequate reduction of a posterior malleolar fragment without soft-tissue or bony interposition in the reduction of ankle fractures. Although not previously reported, posterior tendon entrapment within the posterior malleolus fracture may occur and may require arthroscopic or open techniques to ensure adequate extrication of the tendon to allow for posterior malleolar fracture reduction and fixation. This case report highlights one indication for arthroscopy in the treatment of ankle fractures despite the fact that the tibialis posterior tendon was openly removed. Arthroscopic assistance in acute ankle injuries allows the surgeon to evaluate articular cartilage injuries and ensure there are no interposed structures while checking reduction of the posterior malleolar fracture fragment when present.

Bloom syndrome, also called congenital telangiectatic erythema and stunted growth, was first described by David Bloom in 1954.¹ It is a rare autosomal-recessive disorder (Online Mendelian Inheritance in Man 210900) characterized by specific clinical manifestations including photosensitivity, telangiectatic facial erythema, proportionate growth deficiency, hypogonadism, immunodeficiency, and a tendency to develop various malignancies.² Linkage analysis revealed that the Bloom syndrome gene locus resides on chromosome arm 15q26.1,³ and the BLM gene in this region has been identified as being responsible for the development of Bloom syndrome.^4,5 We report the case of a 12-year-old Chinese girl with Bloom syndrome and detected BLM gene. The evaluation was approved by the Institutional Ethical Review Boards of Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College (Beijing, China).

Case Report

We evaluated a Bloom syndrome family, which consisted of the patient and her parents. The patient was a 12-year-old Chinese girl who was apparently healthy until 3 months of age when her parents noticed an erythematous eruption with blisters on the face. Exacerbation after exposure to sunlight is usual, which results in the eruption becoming prominent in summer and fainter in winter.² Gradually, the patient’s skin lesions became more progressive, extending to the forehead, nose, and ears, with oozing, crusting, atrophy, and telangiectases developing on the face despite treatment. In the last 3 years, no blisters were present on the patient’s face because of her efforts to avoid sun exposure. She had no history of recurrent infections.

On physical examination, the patient was generally healthy with normal intelligence and short stature. She weighed 26 kg and was approximately 122-cm tall. Telangiectatic erythema and slight scaling were noted on the face, which simulated lupus erythematosus (Figures 1A and 1B). She had additional abnormalities including alopecia areata (Figure 1C), eyebrow hair loss, flat nose, reticular pigmentation on the forehead and trunk, and finger swelling. The distal phalanges on all 10 fingers became short and sharpened and the fingernails became wider than they were long (Figure 1D). Laboratory investigations, including a complete blood cell count, liver and kidney function tests, stool examination, serum complement, and albumin and globulin levels, were within reference range.

After informed consent was obtained, a mutation analysis of the BLM gene was performed in the patient and her parents. We used a genomic DNA purification kit to extract genomic DNA from peripheral blood according to the manufacturer’s protocol. Genomic DNA was used to amplify the exons of the BLM gene with intron flanking sequences by polymerase chain reaction with the primer described elsewhere.⁶ After the amplification, the polymerase chain reaction products were purified and the BLM gene was sequenced. Sequence comparisons and analysis were performed using Phred/Phrap/Consed version 12.0.

The patient was found to carry changes in 2 heterozygous nucleotide sites, including c.2603C>T in exon 13 and c.3961G>A in exon 21 of the BLM gene. The patient’s father was found to carry c.2603C>T and her mother carried c.3961G>A (Figure 2).

Comment

Patients with Bloom syndrome have a characteristic clinical appearance that typically includes photosensitivity, telangiectatic facial erythema, and growth deficiency. Telangiectatic erythema of the face develops during infancy or early childhood as red macules or plaques and may simulate lupus erythematosus. The lesions are described as a butterfly rash affecting the bridge of the nose and cheeks but also may involve the margins of the eyelids, forehead, ears, and sometimes the dorsa of the hands and forearms. Moderate and proportionate growth deficiencies develop both in utero and postnatally. Patients with Bloom syndrome characteristically have narrow, slender, distinct facial features with micrognathism and a relatively prominent nose. They usually may have mild microcephaly, meaning the head is longer and narrower than normal.^2,7-10

German and Takebe¹¹ reported 14 Japanese patients with Bloom syndrome. The phenotype differs somewhat from most cases recognized elsewhere in that dolichocephaly was a less constant feature, the facial skin was less prominent, and life-threatening infections were less common. Our patient had typical telangiectatic facial erythema without microcephaly, dolichocephaly, or any infections. She also had some uncommon manifestations such as alopecia areata, eyebrow hair loss, flat nose, reticular pigmentation, and short sharpened distal phalanges with fingernails that were wider than they were long. Although she had no recurrent infections and laboratory tests were within reference range, the alopecia areata and eyebrow hair loss may be associated with an abnormal immune response. The reasons for the short sharpened distal phalanges and the fingernail findings are unclear. The presence of reticular pigmentation also is unclear but may be associated with photosensitivity. Since the BLM gene was discovered to be the disease-causing gene of Bloom syndrome in 1995,^4,5 approximately 70 mutations were reported. The BLM gene encodes for the Bloom syndrome protein, a DNA helicase of the highly conserved RecQ subfamily of helicases, a group of nuclear proteins important in the maintenance of genomic stability.¹²

Mutation analysis of the BLM gene in our patient showed changes in 2 heterozygous nucleotide sites, including c.2603C>T in exon 13 and c.3961G>A in exon 21 of the BLM gene, which altered proline residue with leucine residue at 868 and valine residue with isoleucine residue at 1321, respectively. According to GenBank,^13,14 c.2603C>T and c.3961G>A are single nucleotide polymorphisms of the BLM gene. The genotypic distribution of International HapMap Project¹⁵ showed that C=602/602 and T=0/602 on c.2603 in 301 unrelated Chinese patients and G=585/602 and A=17/602 on c.3961 in 301 unrelated Chinese patients. Because of the low prevalence of genotypes c.2603T and c.3961A in China, the relationship between clinical features and c.2603C>T and c.3961G>A of the BLM gene in our patient requires further study.

In conclusion, we report a patient with Bloom syndrome with uncommon clinical manifestations. Our findings indicate that c.2603C>T and c.3961G>A of the BLM gene may be the pathogenic nature for Bloom syndrome in China.

Acknowledgments

The authors would like to thank the patient and her family for their participation in the study. The authors also thank Li Qi, BA, Beijing, China, for his contribution to the review of the data in the literature.

Bloom syndrome, also called congenital telangiectatic erythema and stunted growth, was first described by David Bloom in 1954.¹ It is a rare autosomal-recessive disorder (Online Mendelian Inheritance in Man 210900) characterized by specific clinical manifestations including photosensitivity, telangiectatic facial erythema, proportionate growth deficiency, hypogonadism, immunodeficiency, and a tendency to develop various malignancies.² Linkage analysis revealed that the Bloom syndrome gene locus resides on chromosome arm 15q26.1,³ and the BLM gene in this region has been identified as being responsible for the development of Bloom syndrome.^4,5 We report the case of a 12-year-old Chinese girl with Bloom syndrome and detected BLM gene. The evaluation was approved by the Institutional Ethical Review Boards of Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College (Beijing, China).

Case Report

We evaluated a Bloom syndrome family, which consisted of the patient and her parents. The patient was a 12-year-old Chinese girl who was apparently healthy until 3 months of age when her parents noticed an erythematous eruption with blisters on the face. Exacerbation after exposure to sunlight is usual, which results in the eruption becoming prominent in summer and fainter in winter.² Gradually, the patient’s skin lesions became more progressive, extending to the forehead, nose, and ears, with oozing, crusting, atrophy, and telangiectases developing on the face despite treatment. In the last 3 years, no blisters were present on the patient’s face because of her efforts to avoid sun exposure. She had no history of recurrent infections.

On physical examination, the patient was generally healthy with normal intelligence and short stature. She weighed 26 kg and was approximately 122-cm tall. Telangiectatic erythema and slight scaling were noted on the face, which simulated lupus erythematosus (Figures 1A and 1B). She had additional abnormalities including alopecia areata (Figure 1C), eyebrow hair loss, flat nose, reticular pigmentation on the forehead and trunk, and finger swelling. The distal phalanges on all 10 fingers became short and sharpened and the fingernails became wider than they were long (Figure 1D). Laboratory investigations, including a complete blood cell count, liver and kidney function tests, stool examination, serum complement, and albumin and globulin levels, were within reference range.

After informed consent was obtained, a mutation analysis of the BLM gene was performed in the patient and her parents. We used a genomic DNA purification kit to extract genomic DNA from peripheral blood according to the manufacturer’s protocol. Genomic DNA was used to amplify the exons of the BLM gene with intron flanking sequences by polymerase chain reaction with the primer described elsewhere.⁶ After the amplification, the polymerase chain reaction products were purified and the BLM gene was sequenced. Sequence comparisons and analysis were performed using Phred/Phrap/Consed version 12.0.

The patient was found to carry changes in 2 heterozygous nucleotide sites, including c.2603C>T in exon 13 and c.3961G>A in exon 21 of the BLM gene. The patient’s father was found to carry c.2603C>T and her mother carried c.3961G>A (Figure 2).

Comment

Patients with Bloom syndrome have a characteristic clinical appearance that typically includes photosensitivity, telangiectatic facial erythema, and growth deficiency. Telangiectatic erythema of the face develops during infancy or early childhood as red macules or plaques and may simulate lupus erythematosus. The lesions are described as a butterfly rash affecting the bridge of the nose and cheeks but also may involve the margins of the eyelids, forehead, ears, and sometimes the dorsa of the hands and forearms. Moderate and proportionate growth deficiencies develop both in utero and postnatally. Patients with Bloom syndrome characteristically have narrow, slender, distinct facial features with micrognathism and a relatively prominent nose. They usually may have mild microcephaly, meaning the head is longer and narrower than normal.^2,7-10

German and Takebe¹¹ reported 14 Japanese patients with Bloom syndrome. The phenotype differs somewhat from most cases recognized elsewhere in that dolichocephaly was a less constant feature, the facial skin was less prominent, and life-threatening infections were less common. Our patient had typical telangiectatic facial erythema without microcephaly, dolichocephaly, or any infections. She also had some uncommon manifestations such as alopecia areata, eyebrow hair loss, flat nose, reticular pigmentation, and short sharpened distal phalanges with fingernails that were wider than they were long. Although she had no recurrent infections and laboratory tests were within reference range, the alopecia areata and eyebrow hair loss may be associated with an abnormal immune response. The reasons for the short sharpened distal phalanges and the fingernail findings are unclear. The presence of reticular pigmentation also is unclear but may be associated with photosensitivity. Since the BLM gene was discovered to be the disease-causing gene of Bloom syndrome in 1995,^4,5 approximately 70 mutations were reported. The BLM gene encodes for the Bloom syndrome protein, a DNA helicase of the highly conserved RecQ subfamily of helicases, a group of nuclear proteins important in the maintenance of genomic stability.¹²

Mutation analysis of the BLM gene in our patient showed changes in 2 heterozygous nucleotide sites, including c.2603C>T in exon 13 and c.3961G>A in exon 21 of the BLM gene, which altered proline residue with leucine residue at 868 and valine residue with isoleucine residue at 1321, respectively. According to GenBank,^13,14 c.2603C>T and c.3961G>A are single nucleotide polymorphisms of the BLM gene. The genotypic distribution of International HapMap Project¹⁵ showed that C=602/602 and T=0/602 on c.2603 in 301 unrelated Chinese patients and G=585/602 and A=17/602 on c.3961 in 301 unrelated Chinese patients. Because of the low prevalence of genotypes c.2603T and c.3961A in China, the relationship between clinical features and c.2603C>T and c.3961G>A of the BLM gene in our patient requires further study.

In conclusion, we report a patient with Bloom syndrome with uncommon clinical manifestations. Our findings indicate that c.2603C>T and c.3961G>A of the BLM gene may be the pathogenic nature for Bloom syndrome in China.

Acknowledgments

The authors would like to thank the patient and her family for their participation in the study. The authors also thank Li Qi, BA, Beijing, China, for his contribution to the review of the data in the literature.

Bloom syndrome, also called congenital telangiectatic erythema and stunted growth, was first described by David Bloom in 1954.¹ It is a rare autosomal-recessive disorder (Online Mendelian Inheritance in Man 210900) characterized by specific clinical manifestations including photosensitivity, telangiectatic facial erythema, proportionate growth deficiency, hypogonadism, immunodeficiency, and a tendency to develop various malignancies.² Linkage analysis revealed that the Bloom syndrome gene locus resides on chromosome arm 15q26.1,³ and the BLM gene in this region has been identified as being responsible for the development of Bloom syndrome.^4,5 We report the case of a 12-year-old Chinese girl with Bloom syndrome and detected BLM gene. The evaluation was approved by the Institutional Ethical Review Boards of Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College (Beijing, China).

Case Report

We evaluated a Bloom syndrome family, which consisted of the patient and her parents. The patient was a 12-year-old Chinese girl who was apparently healthy until 3 months of age when her parents noticed an erythematous eruption with blisters on the face. Exacerbation after exposure to sunlight is usual, which results in the eruption becoming prominent in summer and fainter in winter.² Gradually, the patient’s skin lesions became more progressive, extending to the forehead, nose, and ears, with oozing, crusting, atrophy, and telangiectases developing on the face despite treatment. In the last 3 years, no blisters were present on the patient’s face because of her efforts to avoid sun exposure. She had no history of recurrent infections.

On physical examination, the patient was generally healthy with normal intelligence and short stature. She weighed 26 kg and was approximately 122-cm tall. Telangiectatic erythema and slight scaling were noted on the face, which simulated lupus erythematosus (Figures 1A and 1B). She had additional abnormalities including alopecia areata (Figure 1C), eyebrow hair loss, flat nose, reticular pigmentation on the forehead and trunk, and finger swelling. The distal phalanges on all 10 fingers became short and sharpened and the fingernails became wider than they were long (Figure 1D). Laboratory investigations, including a complete blood cell count, liver and kidney function tests, stool examination, serum complement, and albumin and globulin levels, were within reference range.

After informed consent was obtained, a mutation analysis of the BLM gene was performed in the patient and her parents. We used a genomic DNA purification kit to extract genomic DNA from peripheral blood according to the manufacturer’s protocol. Genomic DNA was used to amplify the exons of the BLM gene with intron flanking sequences by polymerase chain reaction with the primer described elsewhere.⁶ After the amplification, the polymerase chain reaction products were purified and the BLM gene was sequenced. Sequence comparisons and analysis were performed using Phred/Phrap/Consed version 12.0.

The patient was found to carry changes in 2 heterozygous nucleotide sites, including c.2603C>T in exon 13 and c.3961G>A in exon 21 of the BLM gene. The patient’s father was found to carry c.2603C>T and her mother carried c.3961G>A (Figure 2).

Comment

Patients with Bloom syndrome have a characteristic clinical appearance that typically includes photosensitivity, telangiectatic facial erythema, and growth deficiency. Telangiectatic erythema of the face develops during infancy or early childhood as red macules or plaques and may simulate lupus erythematosus. The lesions are described as a butterfly rash affecting the bridge of the nose and cheeks but also may involve the margins of the eyelids, forehead, ears, and sometimes the dorsa of the hands and forearms. Moderate and proportionate growth deficiencies develop both in utero and postnatally. Patients with Bloom syndrome characteristically have narrow, slender, distinct facial features with micrognathism and a relatively prominent nose. They usually may have mild microcephaly, meaning the head is longer and narrower than normal.^2,7-10

German and Takebe¹¹ reported 14 Japanese patients with Bloom syndrome. The phenotype differs somewhat from most cases recognized elsewhere in that dolichocephaly was a less constant feature, the facial skin was less prominent, and life-threatening infections were less common. Our patient had typical telangiectatic facial erythema without microcephaly, dolichocephaly, or any infections. She also had some uncommon manifestations such as alopecia areata, eyebrow hair loss, flat nose, reticular pigmentation, and short sharpened distal phalanges with fingernails that were wider than they were long. Although she had no recurrent infections and laboratory tests were within reference range, the alopecia areata and eyebrow hair loss may be associated with an abnormal immune response. The reasons for the short sharpened distal phalanges and the fingernail findings are unclear. The presence of reticular pigmentation also is unclear but may be associated with photosensitivity. Since the BLM gene was discovered to be the disease-causing gene of Bloom syndrome in 1995,^4,5 approximately 70 mutations were reported. The BLM gene encodes for the Bloom syndrome protein, a DNA helicase of the highly conserved RecQ subfamily of helicases, a group of nuclear proteins important in the maintenance of genomic stability.¹²

Mutation analysis of the BLM gene in our patient showed changes in 2 heterozygous nucleotide sites, including c.2603C>T in exon 13 and c.3961G>A in exon 21 of the BLM gene, which altered proline residue with leucine residue at 868 and valine residue with isoleucine residue at 1321, respectively. According to GenBank,^13,14 c.2603C>T and c.3961G>A are single nucleotide polymorphisms of the BLM gene. The genotypic distribution of International HapMap Project¹⁵ showed that C=602/602 and T=0/602 on c.2603 in 301 unrelated Chinese patients and G=585/602 and A=17/602 on c.3961 in 301 unrelated Chinese patients. Because of the low prevalence of genotypes c.2603T and c.3961A in China, the relationship between clinical features and c.2603C>T and c.3961G>A of the BLM gene in our patient requires further study.

In conclusion, we report a patient with Bloom syndrome with uncommon clinical manifestations. Our findings indicate that c.2603C>T and c.3961G>A of the BLM gene may be the pathogenic nature for Bloom syndrome in China.

Acknowledgments

The authors would like to thank the patient and her family for their participation in the study. The authors also thank Li Qi, BA, Beijing, China, for his contribution to the review of the data in the literature.

Case

A 34-year-old man with a history of polysubstance abuse presented to the ED after he had a seizure during his regular methadone-treatment program meeting. While at the clinic, attendees witnessed the patient experience a loss of consciousness accompanied by generalized shaking movements of his extremities, which lasted for several minutes.

Upon arrival in the ED, the patient stated that he had a mild headache; he was otherwise asymptomatic. Initial vital signs were: blood pressure, 126/80 mm Hg; heart rate, 82 beats/minute; respiratory rate, 16 breaths/minute; and temperature, 97.3°F. Oxygen saturation was 98% on room air, and a finger-stick glucose test was 140 mg/dL. 

Physical examination revealed a small right-sided parietal hematoma. The patient had no tremors and his neurological examination, including mental status, was normal. When reviewing the patient’s medical history and medications in the health record, it was noted that the patient had a prescription for alprazolam for an anxiety disorder. On further questioning, the patient admitted that he had sold his last alprazolam prescription and had not been taking the drug for the past week.

What characterizes the  benzodiazepine withdrawal syndrome?

Although introduced into clinical practice in the 1960s, the potential for dependence and a withdrawal syndrome was not appreciated until the early 1980s. This clinical syndrome can manifest with a wide variety of findings, most commonly with what are termed “rebound effects” or “rebound hyperexcitability.” These effects include anxiety, insomnia or sleep disturbance, tremulousness, irritability, sweating, psychomotor agitation, difficulty in concentration, nausea, weight loss, palpitations, headache, muscular pain and stiffness, or generalized weakness.² More severe manifestations include delirium, seizures, or psychosis. Often, these symptoms and signs may be confused with the very manifestations that prompted the initial use of the BZD, a reemergence of which can exacerbate the withdrawal syndrome.

When does benzodiazepine withdrawal occur?

The exact time course of BZD withdrawal can vary considerably and, unlike alcohol withdrawal (which occurs from a single compound, ethanol), can be difficult to characterize. The onset of withdrawal symptoms is dependent on a number of factors, including the half-life of the BZD involved. For example, delayed onset withdrawal symptoms of up to 3 weeks after cessation of the medication are described with long-acting BZDs such as chlordiazepoxide and diazepam. Conversely, symptoms may present as early as 24 to 48 hours after abrupt termination of BZDs with shorter half-lives, alprazolam and lorazepam. This variable time of onset differs considerably from other withdrawal syndromes, notably ethanol withdrawal. While both syndromes correlate to the individual patient’s severity of dependence, alcohol withdrawal follows a more predictable time course.

Some authors distinguish a rebound syndrome from a true withdrawal syndrome, the former of which is self-limited in nature and the result of cessation of treatment for the primary disease process. In this model, rebound symptoms begin 1 to 4 days after the abrupt cessation or dose reduction of the BZD, and are relatively short-lived, lasting 2 to 3 days.²

What is the appropriate treatment for benzodiazepine withdrawal?

The standard therapy for almost all withdrawal syndromes is reinstitution of the causal agent. A number of non-BZD-based treatment strategies have been investigated, and all have met with limited success. Of these, anticonvulsant drugs such as carbamazepine and valproic acid were initially considered promising based on case reports and small case series.⁴ These medications ultimately proved ineffective in randomized, placebo-controlled studies.⁵ β-Adrenergic antagonists, such as propranolol, have been studied as a method to normalize a patient’s vital signs but also proved nonbeneficial in managing withdrawal.^5,6

The safest and most effective management approach for patients with BZD withdrawal is reinstitution of the BZD followed by a prolonged and gradual tapering until cessation, if that is desired.^1,2,5,6 While all BZDs share structural and mechanistic similarities, there are subtle variations within this class that can affect their pharmacologic effects. These structural differences may result in incomplete cross-tolerance, which may lead to inadequate mitigation of the withdrawal syndrome. For example, previous reports suggest that alprazolam and clonazepam are structurally unique and bind to the BZD receptor with higher affinity than other BZDs. Therefore, while in general any BZD can be used to treat withdrawal from another BZD, it is recommended to treat withdrawal from these two agents with the implicated BZD.

There are, however, limitations to this approach. Namely, some BZDs are only available in oral formulations (eg, alprazolam and clonazepam) or the BZD of choice may not be readily available or on formulary within a given institution. In a patient with a severe withdrawal syndrome where it is not feasible or potentially harmful to administer an oral medication, it is reasonable to provide parenteral (preferably intravenous [IV]) BZD therapy. The optimal approach is to start with a small “standard” dose and titrate to effect while monitoring for adverse effects (eg, oversedation, ventilatory depression). Redosing should be triggered by symptoms or signs, and not performed in a timed or standing-order fashion. If this approach proves ineffective and withdrawal symptoms persist despite adequate BZD therapy, a direct GABA agonist such as propofol is a sensible alternative or adjuvant treatment. This may sound similar to the management of patients with ethanol withdrawal; indeed, this approach is essentially the same, with the exception of the more drawn-out time course.

Case Conclusion

After arrival in the ED, the patient received diazepam 10 mg IV and was subsequently admitted to the hospital for further evaluation. During his hospitalization, the patient was re-started on his usual dose of oral alprazolam.  No further withdrawal syndrome was observed, and he was discharged on hospital day 2 with a plan to slowly taper his alprazolam dose with his outpatient psychiatrist.

Dr Repplinger is a senior medical toxicology fellow in the department of emergency medicine at New York University Langone Medical Center. Dr Nelson, editor of “Case Studies in Toxicology,” is a professor in the department of emergency medicine and director of the medical toxicology fellowship program at the New York University School of Medicine and the New York City Poison Control Center. He is also associate editor, toxicology, of the EMERGENCY MEDICINE editorial board.

Case

A 34-year-old man with a history of polysubstance abuse presented to the ED after he had a seizure during his regular methadone-treatment program meeting. While at the clinic, attendees witnessed the patient experience a loss of consciousness accompanied by generalized shaking movements of his extremities, which lasted for several minutes.

Upon arrival in the ED, the patient stated that he had a mild headache; he was otherwise asymptomatic. Initial vital signs were: blood pressure, 126/80 mm Hg; heart rate, 82 beats/minute; respiratory rate, 16 breaths/minute; and temperature, 97.3°F. Oxygen saturation was 98% on room air, and a finger-stick glucose test was 140 mg/dL. 

Physical examination revealed a small right-sided parietal hematoma. The patient had no tremors and his neurological examination, including mental status, was normal. When reviewing the patient’s medical history and medications in the health record, it was noted that the patient had a prescription for alprazolam for an anxiety disorder. On further questioning, the patient admitted that he had sold his last alprazolam prescription and had not been taking the drug for the past week.

What characterizes the  benzodiazepine withdrawal syndrome?

Although introduced into clinical practice in the 1960s, the potential for dependence and a withdrawal syndrome was not appreciated until the early 1980s. This clinical syndrome can manifest with a wide variety of findings, most commonly with what are termed “rebound effects” or “rebound hyperexcitability.” These effects include anxiety, insomnia or sleep disturbance, tremulousness, irritability, sweating, psychomotor agitation, difficulty in concentration, nausea, weight loss, palpitations, headache, muscular pain and stiffness, or generalized weakness.² More severe manifestations include delirium, seizures, or psychosis. Often, these symptoms and signs may be confused with the very manifestations that prompted the initial use of the BZD, a reemergence of which can exacerbate the withdrawal syndrome.

When does benzodiazepine withdrawal occur?

The exact time course of BZD withdrawal can vary considerably and, unlike alcohol withdrawal (which occurs from a single compound, ethanol), can be difficult to characterize. The onset of withdrawal symptoms is dependent on a number of factors, including the half-life of the BZD involved. For example, delayed onset withdrawal symptoms of up to 3 weeks after cessation of the medication are described with long-acting BZDs such as chlordiazepoxide and diazepam. Conversely, symptoms may present as early as 24 to 48 hours after abrupt termination of BZDs with shorter half-lives, alprazolam and lorazepam. This variable time of onset differs considerably from other withdrawal syndromes, notably ethanol withdrawal. While both syndromes correlate to the individual patient’s severity of dependence, alcohol withdrawal follows a more predictable time course.

Some authors distinguish a rebound syndrome from a true withdrawal syndrome, the former of which is self-limited in nature and the result of cessation of treatment for the primary disease process. In this model, rebound symptoms begin 1 to 4 days after the abrupt cessation or dose reduction of the BZD, and are relatively short-lived, lasting 2 to 3 days.²

What is the appropriate treatment for benzodiazepine withdrawal?

The standard therapy for almost all withdrawal syndromes is reinstitution of the causal agent. A number of non-BZD-based treatment strategies have been investigated, and all have met with limited success. Of these, anticonvulsant drugs such as carbamazepine and valproic acid were initially considered promising based on case reports and small case series.⁴ These medications ultimately proved ineffective in randomized, placebo-controlled studies.⁵ β-Adrenergic antagonists, such as propranolol, have been studied as a method to normalize a patient’s vital signs but also proved nonbeneficial in managing withdrawal.^5,6

The safest and most effective management approach for patients with BZD withdrawal is reinstitution of the BZD followed by a prolonged and gradual tapering until cessation, if that is desired.^1,2,5,6 While all BZDs share structural and mechanistic similarities, there are subtle variations within this class that can affect their pharmacologic effects. These structural differences may result in incomplete cross-tolerance, which may lead to inadequate mitigation of the withdrawal syndrome. For example, previous reports suggest that alprazolam and clonazepam are structurally unique and bind to the BZD receptor with higher affinity than other BZDs. Therefore, while in general any BZD can be used to treat withdrawal from another BZD, it is recommended to treat withdrawal from these two agents with the implicated BZD.

There are, however, limitations to this approach. Namely, some BZDs are only available in oral formulations (eg, alprazolam and clonazepam) or the BZD of choice may not be readily available or on formulary within a given institution. In a patient with a severe withdrawal syndrome where it is not feasible or potentially harmful to administer an oral medication, it is reasonable to provide parenteral (preferably intravenous [IV]) BZD therapy. The optimal approach is to start with a small “standard” dose and titrate to effect while monitoring for adverse effects (eg, oversedation, ventilatory depression). Redosing should be triggered by symptoms or signs, and not performed in a timed or standing-order fashion. If this approach proves ineffective and withdrawal symptoms persist despite adequate BZD therapy, a direct GABA agonist such as propofol is a sensible alternative or adjuvant treatment. This may sound similar to the management of patients with ethanol withdrawal; indeed, this approach is essentially the same, with the exception of the more drawn-out time course.

Case Conclusion

After arrival in the ED, the patient received diazepam 10 mg IV and was subsequently admitted to the hospital for further evaluation. During his hospitalization, the patient was re-started on his usual dose of oral alprazolam.  No further withdrawal syndrome was observed, and he was discharged on hospital day 2 with a plan to slowly taper his alprazolam dose with his outpatient psychiatrist.

Dr Repplinger is a senior medical toxicology fellow in the department of emergency medicine at New York University Langone Medical Center. Dr Nelson, editor of “Case Studies in Toxicology,” is a professor in the department of emergency medicine and director of the medical toxicology fellowship program at the New York University School of Medicine and the New York City Poison Control Center. He is also associate editor, toxicology, of the EMERGENCY MEDICINE editorial board.

Case

A 34-year-old man with a history of polysubstance abuse presented to the ED after he had a seizure during his regular methadone-treatment program meeting. While at the clinic, attendees witnessed the patient experience a loss of consciousness accompanied by generalized shaking movements of his extremities, which lasted for several minutes.

Upon arrival in the ED, the patient stated that he had a mild headache; he was otherwise asymptomatic. Initial vital signs were: blood pressure, 126/80 mm Hg; heart rate, 82 beats/minute; respiratory rate, 16 breaths/minute; and temperature, 97.3°F. Oxygen saturation was 98% on room air, and a finger-stick glucose test was 140 mg/dL. 

Physical examination revealed a small right-sided parietal hematoma. The patient had no tremors and his neurological examination, including mental status, was normal. When reviewing the patient’s medical history and medications in the health record, it was noted that the patient had a prescription for alprazolam for an anxiety disorder. On further questioning, the patient admitted that he had sold his last alprazolam prescription and had not been taking the drug for the past week.

What characterizes the  benzodiazepine withdrawal syndrome?

Although introduced into clinical practice in the 1960s, the potential for dependence and a withdrawal syndrome was not appreciated until the early 1980s. This clinical syndrome can manifest with a wide variety of findings, most commonly with what are termed “rebound effects” or “rebound hyperexcitability.” These effects include anxiety, insomnia or sleep disturbance, tremulousness, irritability, sweating, psychomotor agitation, difficulty in concentration, nausea, weight loss, palpitations, headache, muscular pain and stiffness, or generalized weakness.² More severe manifestations include delirium, seizures, or psychosis. Often, these symptoms and signs may be confused with the very manifestations that prompted the initial use of the BZD, a reemergence of which can exacerbate the withdrawal syndrome.

When does benzodiazepine withdrawal occur?

The exact time course of BZD withdrawal can vary considerably and, unlike alcohol withdrawal (which occurs from a single compound, ethanol), can be difficult to characterize. The onset of withdrawal symptoms is dependent on a number of factors, including the half-life of the BZD involved. For example, delayed onset withdrawal symptoms of up to 3 weeks after cessation of the medication are described with long-acting BZDs such as chlordiazepoxide and diazepam. Conversely, symptoms may present as early as 24 to 48 hours after abrupt termination of BZDs with shorter half-lives, alprazolam and lorazepam. This variable time of onset differs considerably from other withdrawal syndromes, notably ethanol withdrawal. While both syndromes correlate to the individual patient’s severity of dependence, alcohol withdrawal follows a more predictable time course.

Some authors distinguish a rebound syndrome from a true withdrawal syndrome, the former of which is self-limited in nature and the result of cessation of treatment for the primary disease process. In this model, rebound symptoms begin 1 to 4 days after the abrupt cessation or dose reduction of the BZD, and are relatively short-lived, lasting 2 to 3 days.²

What is the appropriate treatment for benzodiazepine withdrawal?

The standard therapy for almost all withdrawal syndromes is reinstitution of the causal agent. A number of non-BZD-based treatment strategies have been investigated, and all have met with limited success. Of these, anticonvulsant drugs such as carbamazepine and valproic acid were initially considered promising based on case reports and small case series.⁴ These medications ultimately proved ineffective in randomized, placebo-controlled studies.⁵ β-Adrenergic antagonists, such as propranolol, have been studied as a method to normalize a patient’s vital signs but also proved nonbeneficial in managing withdrawal.^5,6

The safest and most effective management approach for patients with BZD withdrawal is reinstitution of the BZD followed by a prolonged and gradual tapering until cessation, if that is desired.^1,2,5,6 While all BZDs share structural and mechanistic similarities, there are subtle variations within this class that can affect their pharmacologic effects. These structural differences may result in incomplete cross-tolerance, which may lead to inadequate mitigation of the withdrawal syndrome. For example, previous reports suggest that alprazolam and clonazepam are structurally unique and bind to the BZD receptor with higher affinity than other BZDs. Therefore, while in general any BZD can be used to treat withdrawal from another BZD, it is recommended to treat withdrawal from these two agents with the implicated BZD.

There are, however, limitations to this approach. Namely, some BZDs are only available in oral formulations (eg, alprazolam and clonazepam) or the BZD of choice may not be readily available or on formulary within a given institution. In a patient with a severe withdrawal syndrome where it is not feasible or potentially harmful to administer an oral medication, it is reasonable to provide parenteral (preferably intravenous [IV]) BZD therapy. The optimal approach is to start with a small “standard” dose and titrate to effect while monitoring for adverse effects (eg, oversedation, ventilatory depression). Redosing should be triggered by symptoms or signs, and not performed in a timed or standing-order fashion. If this approach proves ineffective and withdrawal symptoms persist despite adequate BZD therapy, a direct GABA agonist such as propofol is a sensible alternative or adjuvant treatment. This may sound similar to the management of patients with ethanol withdrawal; indeed, this approach is essentially the same, with the exception of the more drawn-out time course.

Case Conclusion

After arrival in the ED, the patient received diazepam 10 mg IV and was subsequently admitted to the hospital for further evaluation. During his hospitalization, the patient was re-started on his usual dose of oral alprazolam.  No further withdrawal syndrome was observed, and he was discharged on hospital day 2 with a plan to slowly taper his alprazolam dose with his outpatient psychiatrist.

Dr Repplinger is a senior medical toxicology fellow in the department of emergency medicine at New York University Langone Medical Center. Dr Nelson, editor of “Case Studies in Toxicology,” is a professor in the department of emergency medicine and director of the medical toxicology fellowship program at the New York University School of Medicine and the New York City Poison Control Center. He is also associate editor, toxicology, of the EMERGENCY MEDICINE editorial board.

THE CASE

A 36-year-old man sought care at our family medicine clinic for knee pain that he’d had for the past year. He denied any previous injury or trauma to the knee. The pain affected the posterolateral left knee and was aggravated by squatting and deep flexion. Daily activities did not bother him, but skiing, golfing, mountain biking, and lifting weights worsened the pain. His pain had gradually become more severe and frequent. He denied any mechanical symptoms such as catching, popping, or locking.

Examination of his left knee demonstrated range of motion from 0 to 120 degrees; further flexion caused significant pain. McMurray and Thessaly tests were positive for posterolateral pain, particularly with knee flexion >120 degrees. Physical examination was otherwise unremarkable. Standard x-rays of the left knee were normal. Our patient completed a month of physical therapy, but his symptoms did not improve.

THE DIAGNOSIS

After the patient completed physical therapy, magnetic resonance imaging (MRI) was performed. The MRI did not reveal any left knee effusion, and the menisci, collateral ligaments, and cartilage surfaces were normal. And, while the cruciate ligaments were intact, a large pericruciate ganglion cyst was noted (FIGURES 1 AND 2).

DISCUSSION

Ganglion cysts are dense, encapsulated structures filled with clear viscous fluid that often arise adjacent to tendon sheaths or joint capsules, most commonly over the dorsum of the hand.¹ Intra-articular ganglia involving the cruciate ligaments of the knee are relatively uncommon.² The estimated prevalence of cruciate ligament ganglion cysts at arthroscopy is 0.2% to 1.9%; similar rates have been demonstrated with MRI.^3-6 There are more reported cases of these cysts involving the anterior cruciate ligament (ACL) compared to those affecting the posterior cruciate ligament (PCL).^2,6

Classification of these cysts is based on relative location with respect to the ligaments. Type 1 cysts originate anterior to the ACL; type 2, between the ACL and PCL; and type 3, posterior to the PCL.^6,7 Cruciate ligament ganglion cysts are more common in men, are typically discovered between age 20 and 40, and are usually incidental findings.⁸

The pathogenesis of ganglion cyst formation is unknown.^1,6,7 The most widely accepted theory is that ganglion cysts result from mucinous degeneration of connective tissue in areas of repetitive stress.^1,6,7 Other theories suggest hyaluronic acid production secondary to mesenchymal stem cell proliferation within the ligaments, synovial tissue herniation, or congenital translocation of synovial tissue as possible etiologies.^2,6,7

Concurrent pathologies such as meniscal tears or chondral lesions may also be present; however, there is some disagreement as to what role, if any, antecedent trauma has in the pathogenesis of cyst formation.^1,6 Several investigators have suggested that prior knee trauma is a likely risk factor.^2,8,9 

In most patients, cruciate ligament ganglion cysts are asymptomatic.⁷ The most common presenting symptom is nonspecific pain that is exacerbated by activity, such as stair climbing, squatting, or other activities that require extreme flexion or extension of the knee.^6,9 Other possible symptoms include limited range of motion (extension block with ACL involvement, limited flexion with PCL lesions), a catching or locking sensation, instability, or joint line tenderness.^5,6 A palpable mass on physical exam is not usually present.⁶ Some investigators suggest that larger lesions and those closer to the femoral ligamentous attachments are more likely to cause symptoms.⁵

Cruciate ligament ganglion cysts can be an easily overlooked source of a patient’s symptoms because they often mimic more common pathologies.² The differential diagnosis of cruciate ligament ganglion cysts and posterior knee pain includes any other intra-articular cysts (eg, meniscal cysts), posterior meniscal tear, popliteus tendinopathy, or neoplasms (eg, hemangioma and synovial sarcoma).^2,6

MRI is the best method of diagnosis

Because the symptoms of cruciate ligament ganglion cysts are variable and nonspecific, the diagnosis is rarely made on clinical grounds alone.¹ The best method of evaluating suspected intra-articular pathologies such as cruciate ligament ganglion cysts is MRI.^5,10

Cruciate ligament ganglion cysts are more common in men and are usually incidental findings.

Cruciate ligament ganglion cysts typically follow fluid signal on all sequences, with low signal intensity on T1-weighted images and high signal intensity on T2-weighted images.^1,2,5,6 A pericruciate location with a multilocular appearance is usually sufficient evidence to make a diagnosis. However, solid or semi-solid pathologies (such as synovial cell sarcoma, synovial hemangioma, or synovial chondromatosis) can have similar signal intensity.

If necessary, intravenous contrast can be helpful; a lack of central contrast enhancement can differentiate ganglion cysts from other solid, enhancing, or partially enhancing lesions. Other diagnostic modalities, such as ultrasound, computed tomography (CT), and diagnostic arthroscopy, are less practical and have a wide range of sensitivity and specificity.^5,6,10

Arthroscopic excision is the treatment of choice

Asymptomatic cruciate ligament ganglion cysts are usually managed with clinical follow-up. For patients with symptomatic cysts, ultrasound- or CT-guided percutaneous cyst aspiration may temporarily improve symptoms, but recurrence rates have not been well studied.^2,6,9,10 Additionally, accessibility to cysts in this location via these approaches is limited. Arthroscopic excision of the cyst is the treatment of choice for symptomatic cases.^1,2,5,6,10

Our patient underwent arthroscopic cyst resection, which resulted in complete resolution of his symptoms. In 3 months, he returned to his regular physical activities with no pain or discomfort. One year later, he remained asymptomatic.

THE TAKEAWAY

Cruciate ligament ganglion cysts are a rare cause of posterior knee pain. An MRI is the best diagnostic modality to evaluate and confirm the diagnosis, as well as rule out other pathologies. The treatment of choice for symptomatic cases is arthroscopic excision of the cyst.

THE CASE

A 36-year-old man sought care at our family medicine clinic for knee pain that he’d had for the past year. He denied any previous injury or trauma to the knee. The pain affected the posterolateral left knee and was aggravated by squatting and deep flexion. Daily activities did not bother him, but skiing, golfing, mountain biking, and lifting weights worsened the pain. His pain had gradually become more severe and frequent. He denied any mechanical symptoms such as catching, popping, or locking.

Examination of his left knee demonstrated range of motion from 0 to 120 degrees; further flexion caused significant pain. McMurray and Thessaly tests were positive for posterolateral pain, particularly with knee flexion >120 degrees. Physical examination was otherwise unremarkable. Standard x-rays of the left knee were normal. Our patient completed a month of physical therapy, but his symptoms did not improve.

THE DIAGNOSIS

After the patient completed physical therapy, magnetic resonance imaging (MRI) was performed. The MRI did not reveal any left knee effusion, and the menisci, collateral ligaments, and cartilage surfaces were normal. And, while the cruciate ligaments were intact, a large pericruciate ganglion cyst was noted (FIGURES 1 AND 2).

DISCUSSION

Ganglion cysts are dense, encapsulated structures filled with clear viscous fluid that often arise adjacent to tendon sheaths or joint capsules, most commonly over the dorsum of the hand.¹ Intra-articular ganglia involving the cruciate ligaments of the knee are relatively uncommon.² The estimated prevalence of cruciate ligament ganglion cysts at arthroscopy is 0.2% to 1.9%; similar rates have been demonstrated with MRI.^3-6 There are more reported cases of these cysts involving the anterior cruciate ligament (ACL) compared to those affecting the posterior cruciate ligament (PCL).^2,6

Classification of these cysts is based on relative location with respect to the ligaments. Type 1 cysts originate anterior to the ACL; type 2, between the ACL and PCL; and type 3, posterior to the PCL.^6,7 Cruciate ligament ganglion cysts are more common in men, are typically discovered between age 20 and 40, and are usually incidental findings.⁸

The pathogenesis of ganglion cyst formation is unknown.^1,6,7 The most widely accepted theory is that ganglion cysts result from mucinous degeneration of connective tissue in areas of repetitive stress.^1,6,7 Other theories suggest hyaluronic acid production secondary to mesenchymal stem cell proliferation within the ligaments, synovial tissue herniation, or congenital translocation of synovial tissue as possible etiologies.^2,6,7

Concurrent pathologies such as meniscal tears or chondral lesions may also be present; however, there is some disagreement as to what role, if any, antecedent trauma has in the pathogenesis of cyst formation.^1,6 Several investigators have suggested that prior knee trauma is a likely risk factor.^2,8,9 

In most patients, cruciate ligament ganglion cysts are asymptomatic.⁷ The most common presenting symptom is nonspecific pain that is exacerbated by activity, such as stair climbing, squatting, or other activities that require extreme flexion or extension of the knee.^6,9 Other possible symptoms include limited range of motion (extension block with ACL involvement, limited flexion with PCL lesions), a catching or locking sensation, instability, or joint line tenderness.^5,6 A palpable mass on physical exam is not usually present.⁶ Some investigators suggest that larger lesions and those closer to the femoral ligamentous attachments are more likely to cause symptoms.⁵

Cruciate ligament ganglion cysts can be an easily overlooked source of a patient’s symptoms because they often mimic more common pathologies.² The differential diagnosis of cruciate ligament ganglion cysts and posterior knee pain includes any other intra-articular cysts (eg, meniscal cysts), posterior meniscal tear, popliteus tendinopathy, or neoplasms (eg, hemangioma and synovial sarcoma).^2,6

MRI is the best method of diagnosis

Because the symptoms of cruciate ligament ganglion cysts are variable and nonspecific, the diagnosis is rarely made on clinical grounds alone.¹ The best method of evaluating suspected intra-articular pathologies such as cruciate ligament ganglion cysts is MRI.^5,10

Cruciate ligament ganglion cysts are more common in men and are usually incidental findings.

Cruciate ligament ganglion cysts typically follow fluid signal on all sequences, with low signal intensity on T1-weighted images and high signal intensity on T2-weighted images.^1,2,5,6 A pericruciate location with a multilocular appearance is usually sufficient evidence to make a diagnosis. However, solid or semi-solid pathologies (such as synovial cell sarcoma, synovial hemangioma, or synovial chondromatosis) can have similar signal intensity.

If necessary, intravenous contrast can be helpful; a lack of central contrast enhancement can differentiate ganglion cysts from other solid, enhancing, or partially enhancing lesions. Other diagnostic modalities, such as ultrasound, computed tomography (CT), and diagnostic arthroscopy, are less practical and have a wide range of sensitivity and specificity.^5,6,10

Arthroscopic excision is the treatment of choice

Asymptomatic cruciate ligament ganglion cysts are usually managed with clinical follow-up. For patients with symptomatic cysts, ultrasound- or CT-guided percutaneous cyst aspiration may temporarily improve symptoms, but recurrence rates have not been well studied.^2,6,9,10 Additionally, accessibility to cysts in this location via these approaches is limited. Arthroscopic excision of the cyst is the treatment of choice for symptomatic cases.^1,2,5,6,10

Our patient underwent arthroscopic cyst resection, which resulted in complete resolution of his symptoms. In 3 months, he returned to his regular physical activities with no pain or discomfort. One year later, he remained asymptomatic.

THE TAKEAWAY

Cruciate ligament ganglion cysts are a rare cause of posterior knee pain. An MRI is the best diagnostic modality to evaluate and confirm the diagnosis, as well as rule out other pathologies. The treatment of choice for symptomatic cases is arthroscopic excision of the cyst.

THE CASE

A 36-year-old man sought care at our family medicine clinic for knee pain that he’d had for the past year. He denied any previous injury or trauma to the knee. The pain affected the posterolateral left knee and was aggravated by squatting and deep flexion. Daily activities did not bother him, but skiing, golfing, mountain biking, and lifting weights worsened the pain. His pain had gradually become more severe and frequent. He denied any mechanical symptoms such as catching, popping, or locking.

Examination of his left knee demonstrated range of motion from 0 to 120 degrees; further flexion caused significant pain. McMurray and Thessaly tests were positive for posterolateral pain, particularly with knee flexion >120 degrees. Physical examination was otherwise unremarkable. Standard x-rays of the left knee were normal. Our patient completed a month of physical therapy, but his symptoms did not improve.

THE DIAGNOSIS

After the patient completed physical therapy, magnetic resonance imaging (MRI) was performed. The MRI did not reveal any left knee effusion, and the menisci, collateral ligaments, and cartilage surfaces were normal. And, while the cruciate ligaments were intact, a large pericruciate ganglion cyst was noted (FIGURES 1 AND 2).

DISCUSSION

Ganglion cysts are dense, encapsulated structures filled with clear viscous fluid that often arise adjacent to tendon sheaths or joint capsules, most commonly over the dorsum of the hand.¹ Intra-articular ganglia involving the cruciate ligaments of the knee are relatively uncommon.² The estimated prevalence of cruciate ligament ganglion cysts at arthroscopy is 0.2% to 1.9%; similar rates have been demonstrated with MRI.^3-6 There are more reported cases of these cysts involving the anterior cruciate ligament (ACL) compared to those affecting the posterior cruciate ligament (PCL).^2,6

Classification of these cysts is based on relative location with respect to the ligaments. Type 1 cysts originate anterior to the ACL; type 2, between the ACL and PCL; and type 3, posterior to the PCL.^6,7 Cruciate ligament ganglion cysts are more common in men, are typically discovered between age 20 and 40, and are usually incidental findings.⁸

The pathogenesis of ganglion cyst formation is unknown.^1,6,7 The most widely accepted theory is that ganglion cysts result from mucinous degeneration of connective tissue in areas of repetitive stress.^1,6,7 Other theories suggest hyaluronic acid production secondary to mesenchymal stem cell proliferation within the ligaments, synovial tissue herniation, or congenital translocation of synovial tissue as possible etiologies.^2,6,7

Concurrent pathologies such as meniscal tears or chondral lesions may also be present; however, there is some disagreement as to what role, if any, antecedent trauma has in the pathogenesis of cyst formation.^1,6 Several investigators have suggested that prior knee trauma is a likely risk factor.^2,8,9 

In most patients, cruciate ligament ganglion cysts are asymptomatic.⁷ The most common presenting symptom is nonspecific pain that is exacerbated by activity, such as stair climbing, squatting, or other activities that require extreme flexion or extension of the knee.^6,9 Other possible symptoms include limited range of motion (extension block with ACL involvement, limited flexion with PCL lesions), a catching or locking sensation, instability, or joint line tenderness.^5,6 A palpable mass on physical exam is not usually present.⁶ Some investigators suggest that larger lesions and those closer to the femoral ligamentous attachments are more likely to cause symptoms.⁵

Cruciate ligament ganglion cysts can be an easily overlooked source of a patient’s symptoms because they often mimic more common pathologies.² The differential diagnosis of cruciate ligament ganglion cysts and posterior knee pain includes any other intra-articular cysts (eg, meniscal cysts), posterior meniscal tear, popliteus tendinopathy, or neoplasms (eg, hemangioma and synovial sarcoma).^2,6

MRI is the best method of diagnosis

Because the symptoms of cruciate ligament ganglion cysts are variable and nonspecific, the diagnosis is rarely made on clinical grounds alone.¹ The best method of evaluating suspected intra-articular pathologies such as cruciate ligament ganglion cysts is MRI.^5,10

Cruciate ligament ganglion cysts are more common in men and are usually incidental findings.

Cruciate ligament ganglion cysts typically follow fluid signal on all sequences, with low signal intensity on T1-weighted images and high signal intensity on T2-weighted images.^1,2,5,6 A pericruciate location with a multilocular appearance is usually sufficient evidence to make a diagnosis. However, solid or semi-solid pathologies (such as synovial cell sarcoma, synovial hemangioma, or synovial chondromatosis) can have similar signal intensity.

If necessary, intravenous contrast can be helpful; a lack of central contrast enhancement can differentiate ganglion cysts from other solid, enhancing, or partially enhancing lesions. Other diagnostic modalities, such as ultrasound, computed tomography (CT), and diagnostic arthroscopy, are less practical and have a wide range of sensitivity and specificity.^5,6,10

Arthroscopic excision is the treatment of choice

Asymptomatic cruciate ligament ganglion cysts are usually managed with clinical follow-up. For patients with symptomatic cysts, ultrasound- or CT-guided percutaneous cyst aspiration may temporarily improve symptoms, but recurrence rates have not been well studied.^2,6,9,10 Additionally, accessibility to cysts in this location via these approaches is limited. Arthroscopic excision of the cyst is the treatment of choice for symptomatic cases.^1,2,5,6,10

Our patient underwent arthroscopic cyst resection, which resulted in complete resolution of his symptoms. In 3 months, he returned to his regular physical activities with no pain or discomfort. One year later, he remained asymptomatic.

THE TAKEAWAY

Cruciate ligament ganglion cysts are a rare cause of posterior knee pain. An MRI is the best diagnostic modality to evaluate and confirm the diagnosis, as well as rule out other pathologies. The treatment of choice for symptomatic cases is arthroscopic excision of the cyst.

THE CASES

CASE 1 ›  A 15-month-old boy was brought to our center for plastic surgery after being referred by his general practitioner (GP). The patient had a non-healing lesion on his umbilicus that had been present since birth. It had remained the same size, but bled occasionally. The GP initially presumed the lesion was a granuloma and treated it with silver nitrate cautery, but this did not eradicate it.

After talking with the boy’s mother further, we learned that there had been a constant oozing from the area since birth and that the lesion protruded slightly from the abdomen when the child cried. The boy had congenital heart disease, but his bowel and genitourinary history were normal. A clinical examination revealed pink, moist tissue herniating from the umbilicus with surrounding abdominal fullness when the boy stood up (FIGURE 1A). An ultrasound showed a focal 19 x 7 mm complex area around the umbilicus with no definite track. The lesion was surgically removed. Histology revealed a completely excised vitellointestinal duct remnant.

CASE 2 ›  A 6-year-old boy with a history of attention-deficit/hyperactivity disorder was brought to our clinic with a non-healing umbilical lesion after being referred by his GP. The lesion had been present since birth and had failed to resolve despite several attempts to treat it with silver nitrate cautery. Clinically, the patient appeared to have a granulomatous umbilical polyp (FIGURE 1B). The patient underwent surgical excision of the lesion. Histological analysis revealed a completely excised vitellointestinal duct remnant (FIGURE 2).

DISCUSSION

The vitellointestinal duct (VID), also called the omphalomesenteric duct (OMD), connects the alimentary canal and the yolk sac in early embryogenesis. Failure of involution of the duct results in abnormalities such as Meckel’s diverticulum, cysts, and polyps.

VID anomalies occur in approximately 2% of newborns; a small percentage of these have patent connections to the intestine.¹ Parents are often the first to notice the abnormality and will typically see a reddish protrusion around the umbilicus or a persistent serous discharge around the umbilicus soon after birth.

VID remnants are similar in presentation to benign granulomas or granulation tissue, which are benign lesions that present in the first few weeks of life. Granulomas are reddish in color, bleed minimally when irritated by trauma, and respond well to silver nitrate cautery.² When the lesion fails to respond to treatment, an alternative diagnosis should be investigated further.

Ultrasonography is the best way to evaluate a suspected VID remnant

A suspected VID remnant should first be assessed with ultrasonography to determine the extent of the remnant and guide surgical treatment. Ultrasonography can also delineate the relationship of these congenital remnants with the umbilicus and bladder.³

Potential complications that can arise from these lesions include an intestinal hernia, intussusception, volvulus, abdominal pain, or a persistent discharge that can lead to infection.³ Mortality following complications is significantly high.⁴

Although the etiology of patent VIDs and their remnants remains unknown, the presence of such ducts is associated with other congenital anomalies, including Down Syndrome, structural cardiac malformation, conduction abnormalities, and cleft lip and palate.^5-7 Therefore, additional history taking and examinations may be required to identify these associated pathologies. In Case 1, the 15-month-old boy had congenital heart disease.

Surgical excision will prevent complications

A simple surgical excision should be performed for VID remnants. The prognosis is excellent when such procedures are performed in the non-acute setting. Some debate exists as to whether all remnants require formal abdominal exploration.^8,9

Treatment of patent VIDs requires surgical excision of the duct, with or without a segment of the small bowel, to obliterate the connection.¹⁰ Reconstruction of the umbilicus is then performed, depending on the surgical technique used.

Vitellointestinal duct remnants are similar in presentation to benign granulomasor granulation tissue.

Our patients both made complete recoveries following their surgeries with resolution of their symptoms.

THE TAKEAWAY

Consider a VID remnant as part of the differential diagnosis for any patient who has what appears to be a granulomatous umbilical lesion. Order ultrasonography to evaluate a suspected VID, especially for lesions that fail to respond to 2 or 3 silver nitrate treatments. Surgical excision of a VID remnant is usually curative.

THE CASES

CASE 1 ›  A 15-month-old boy was brought to our center for plastic surgery after being referred by his general practitioner (GP). The patient had a non-healing lesion on his umbilicus that had been present since birth. It had remained the same size, but bled occasionally. The GP initially presumed the lesion was a granuloma and treated it with silver nitrate cautery, but this did not eradicate it.

After talking with the boy’s mother further, we learned that there had been a constant oozing from the area since birth and that the lesion protruded slightly from the abdomen when the child cried. The boy had congenital heart disease, but his bowel and genitourinary history were normal. A clinical examination revealed pink, moist tissue herniating from the umbilicus with surrounding abdominal fullness when the boy stood up (FIGURE 1A). An ultrasound showed a focal 19 x 7 mm complex area around the umbilicus with no definite track. The lesion was surgically removed. Histology revealed a completely excised vitellointestinal duct remnant.

CASE 2 ›  A 6-year-old boy with a history of attention-deficit/hyperactivity disorder was brought to our clinic with a non-healing umbilical lesion after being referred by his GP. The lesion had been present since birth and had failed to resolve despite several attempts to treat it with silver nitrate cautery. Clinically, the patient appeared to have a granulomatous umbilical polyp (FIGURE 1B). The patient underwent surgical excision of the lesion. Histological analysis revealed a completely excised vitellointestinal duct remnant (FIGURE 2).

DISCUSSION

The vitellointestinal duct (VID), also called the omphalomesenteric duct (OMD), connects the alimentary canal and the yolk sac in early embryogenesis. Failure of involution of the duct results in abnormalities such as Meckel’s diverticulum, cysts, and polyps.

VID anomalies occur in approximately 2% of newborns; a small percentage of these have patent connections to the intestine.¹ Parents are often the first to notice the abnormality and will typically see a reddish protrusion around the umbilicus or a persistent serous discharge around the umbilicus soon after birth.

VID remnants are similar in presentation to benign granulomas or granulation tissue, which are benign lesions that present in the first few weeks of life. Granulomas are reddish in color, bleed minimally when irritated by trauma, and respond well to silver nitrate cautery.² When the lesion fails to respond to treatment, an alternative diagnosis should be investigated further.

Ultrasonography is the best way to evaluate a suspected VID remnant

A suspected VID remnant should first be assessed with ultrasonography to determine the extent of the remnant and guide surgical treatment. Ultrasonography can also delineate the relationship of these congenital remnants with the umbilicus and bladder.³

Potential complications that can arise from these lesions include an intestinal hernia, intussusception, volvulus, abdominal pain, or a persistent discharge that can lead to infection.³ Mortality following complications is significantly high.⁴

Although the etiology of patent VIDs and their remnants remains unknown, the presence of such ducts is associated with other congenital anomalies, including Down Syndrome, structural cardiac malformation, conduction abnormalities, and cleft lip and palate.^5-7 Therefore, additional history taking and examinations may be required to identify these associated pathologies. In Case 1, the 15-month-old boy had congenital heart disease.

Surgical excision will prevent complications

A simple surgical excision should be performed for VID remnants. The prognosis is excellent when such procedures are performed in the non-acute setting. Some debate exists as to whether all remnants require formal abdominal exploration.^8,9

Treatment of patent VIDs requires surgical excision of the duct, with or without a segment of the small bowel, to obliterate the connection.¹⁰ Reconstruction of the umbilicus is then performed, depending on the surgical technique used.

Vitellointestinal duct remnants are similar in presentation to benign granulomasor granulation tissue.

Our patients both made complete recoveries following their surgeries with resolution of their symptoms.

THE TAKEAWAY

Consider a VID remnant as part of the differential diagnosis for any patient who has what appears to be a granulomatous umbilical lesion. Order ultrasonography to evaluate a suspected VID, especially for lesions that fail to respond to 2 or 3 silver nitrate treatments. Surgical excision of a VID remnant is usually curative.

THE CASES

CASE 1 ›  A 15-month-old boy was brought to our center for plastic surgery after being referred by his general practitioner (GP). The patient had a non-healing lesion on his umbilicus that had been present since birth. It had remained the same size, but bled occasionally. The GP initially presumed the lesion was a granuloma and treated it with silver nitrate cautery, but this did not eradicate it.

After talking with the boy’s mother further, we learned that there had been a constant oozing from the area since birth and that the lesion protruded slightly from the abdomen when the child cried. The boy had congenital heart disease, but his bowel and genitourinary history were normal. A clinical examination revealed pink, moist tissue herniating from the umbilicus with surrounding abdominal fullness when the boy stood up (FIGURE 1A). An ultrasound showed a focal 19 x 7 mm complex area around the umbilicus with no definite track. The lesion was surgically removed. Histology revealed a completely excised vitellointestinal duct remnant.

CASE 2 ›  A 6-year-old boy with a history of attention-deficit/hyperactivity disorder was brought to our clinic with a non-healing umbilical lesion after being referred by his GP. The lesion had been present since birth and had failed to resolve despite several attempts to treat it with silver nitrate cautery. Clinically, the patient appeared to have a granulomatous umbilical polyp (FIGURE 1B). The patient underwent surgical excision of the lesion. Histological analysis revealed a completely excised vitellointestinal duct remnant (FIGURE 2).

DISCUSSION

The vitellointestinal duct (VID), also called the omphalomesenteric duct (OMD), connects the alimentary canal and the yolk sac in early embryogenesis. Failure of involution of the duct results in abnormalities such as Meckel’s diverticulum, cysts, and polyps.

VID anomalies occur in approximately 2% of newborns; a small percentage of these have patent connections to the intestine.¹ Parents are often the first to notice the abnormality and will typically see a reddish protrusion around the umbilicus or a persistent serous discharge around the umbilicus soon after birth.

VID remnants are similar in presentation to benign granulomas or granulation tissue, which are benign lesions that present in the first few weeks of life. Granulomas are reddish in color, bleed minimally when irritated by trauma, and respond well to silver nitrate cautery.² When the lesion fails to respond to treatment, an alternative diagnosis should be investigated further.

Ultrasonography is the best way to evaluate a suspected VID remnant

A suspected VID remnant should first be assessed with ultrasonography to determine the extent of the remnant and guide surgical treatment. Ultrasonography can also delineate the relationship of these congenital remnants with the umbilicus and bladder.³

Potential complications that can arise from these lesions include an intestinal hernia, intussusception, volvulus, abdominal pain, or a persistent discharge that can lead to infection.³ Mortality following complications is significantly high.⁴

Although the etiology of patent VIDs and their remnants remains unknown, the presence of such ducts is associated with other congenital anomalies, including Down Syndrome, structural cardiac malformation, conduction abnormalities, and cleft lip and palate.^5-7 Therefore, additional history taking and examinations may be required to identify these associated pathologies. In Case 1, the 15-month-old boy had congenital heart disease.

Surgical excision will prevent complications

A simple surgical excision should be performed for VID remnants. The prognosis is excellent when such procedures are performed in the non-acute setting. Some debate exists as to whether all remnants require formal abdominal exploration.^8,9

Treatment of patent VIDs requires surgical excision of the duct, with or without a segment of the small bowel, to obliterate the connection.¹⁰ Reconstruction of the umbilicus is then performed, depending on the surgical technique used.

Vitellointestinal duct remnants are similar in presentation to benign granulomasor granulation tissue.

Our patients both made complete recoveries following their surgeries with resolution of their symptoms.

THE TAKEAWAY

Consider a VID remnant as part of the differential diagnosis for any patient who has what appears to be a granulomatous umbilical lesion. Order ultrasonography to evaluate a suspected VID, especially for lesions that fail to respond to 2 or 3 silver nitrate treatments. Surgical excision of a VID remnant is usually curative.

Fibrous dysplasia is a developmental abnormality caused by excessive proliferation of immature spindle-cell fibrous tissues in bones. It is characterized by benign bony growths, which can lead to local swelling, bony deformities, and lytic conversion, predisposing the bone to pathologic fractures. Although this process can occur in cortical bone, it primarily affects the trabecular bone, leading to enlargement and expansion from within the medullary space. Malignant transformation to osteosarcoma or fibrosarcoma can occur, although this is exceedingly rare (<0.5%).^1,2

This case report describes a patient who presented with an expansile lytic mass in a lumbar transverse process that was postoperatively identified on pathology as monostotic fibrous dysplasia. Such lesions that involve the transverse processes are rare and have been associated with pain and significant discomfort.^3-5 This is the first reported case of a transverse process fibrous dysplasia causing urinary retention and neurologic symptoms simultaneously. The patient provided written informed consent for print and electronic publication of this case report.

Case Report

History

A 52-year-old black man presented to us with 6 to 8 months of increasing right flank pain, difficulty with urination, and right lower extremity pain in the area of his anterior thigh. He also complained of “buckling” of his thigh with ambulation. On review of systems, the patient denied any fevers, chills, headache, changes in weight or vision, or hearing problems. He had no systemic symptoms except for 6 months of frequent urinary tract infections and difficulty emptying his bladder, which resulted in urinary retention. He denied any significant medical history and denied any use of alcohol or tobacco.

Physical Examination

On physical examination, the patient was a well-appearing 52-year-old man in no apparent distress. No signs of gross deformity, erythema, ecchymosis, or infection were noted upon examination of his lower extremities. His motor examination was within normal limits from L2 to S1. However, both fine and gross sensation were decreased in the L3 distribution. Sensation was intact to the remaining nerve-root distributions. The Babinski sign was negative for both lower extremities, and clonus was within physiologic limits. Examination of his gait was notable for quadriceps buckling with ambulation.

Radiographic Examination

The patient initially presented to his primary care physician, who evaluated his symptoms with a computed tomography scan of his abdomen and pelvis. This showed a mass of the right L3 transverse process (Figure 1). The patient was referred to us for further management of this lesion. Dedicated magnetic resonance imaging of his lumbar spine was performed, showing an expansile, lytic, homogeneous mass in the patient’s right L3 transverse process. The mass showed a significant mass effect, compressing the exiting nerve roots and, presumably, his right ureter (Figure 2). A bone scan showed monostotic disease. The patient had failed conservative management, including physical therapy and anti-inflammatory medications. His right-sided radiculopathy was worsening, and he complained that the pain was affecting his quality of life and limiting his performance of his daily activities. A pain management specialist was requested to better manage his pain. Considering progression of his condition, surgical management was discussed, leading to a planned biopsy and resection of the mass.

Surgical Procedure

The patient was taken into the operating room and positioned prone on a Jackson table with a Wilson frame. Fluoroscopy was used to localize the right L3 transverse process. An incision was made over the right L3 transverse process and a Wiltse intramuscular approach was performed. After the right L3 transverse process was identified, the soft tissue from the transverse process was retracted in all directions, including medially up to the pedicle. The intertransverse ligament was detached from both the cephalad and caudal edges of the transverse process. We used a Woodson elevator to perform subperiosteal dissection to remove the soft tissue circumferentially. After dissection, we placed a Cobb elevator to protect the rostral and caudal soft tissue and used a high-speed burr to amputate the lytic transverse process at its base. The transverse process was removed en bloc (Figure 3) and sent for frozen pathologic evaluation (Figure 4). After the diagnosis of a benign lesion, the wound was closed in layers.

Complete resolution of both urinary and neurologic symptoms were immediately noted and up to 1 month postoperatively.

Discussion

Primary bone tumors of the spine are rare, with a reported incidence of 2.5 to 8.5 per 100,000 people per year.⁶ The estimated incidence of benign primary tumors involving the spine accounts for about 1% of all primary skeletal tumors and nearly 5% for malignant tumors.^7-9 In contrast, secondary tumors involving the bony spinal column are relatively common. Postmortem studies indicate up to 70% of cancer patients demonstrate axial skeletal involvement.^10,11 The most commonly encountered benign tumors affecting the spine include giant cell tumors, osteoid osteomas, osteoblastomas, and hemangiomas. Chordomas are frequently reported as the most common malignant primary spine neoplasms. Of all primary benign bone lesions, fibrous dysplasia accounts for approximately 1.4%.⁸

Primary and secondary malignant osseous tumors have a predilection for the anterior column, and primary benign lesions usually affect the posterior column.^8,12-14 Because of the greater blood supply and more direct communication with the viscera via the Batson plexus, the anterior column is most likely to be seeded by metastatic disease. Similarly, hemangiomas and multiple myeloma are typically located in the anterior column, most likely because of the more abundant blood supply there. Chordomas are also found in this cancellous anterior column. Osteoid osteoma, osteoblastoma, and aneurysmal bone cysts are found within the more cortical architecture of posterior elements. The location of this patient’s lesion within the transverse process elevates confidence in the diagnosis of a benign lesion.

The conventional, isolated form of fibrous dysplasia was originally described in 1942 by Lichtenstein and Jaffe.² They described 15 cases of benign “nonosteogenic fibromas” near the ends of long bones in young patients. Monostotic fibrous dysplasia constitutes the majority of these cases, approximately 80%.^1,2,8,15 Fibrous dysplasia may also present as part of McCune-Albright syndrome, in which case it is associated with precocious puberty and café au lait spots. Less commonly, they are associated with intramuscular myxomas, as in Mazabraud syndrome. The lesions in these syndromes are typically polyostotic. In all forms, fibrous dysplasia develops from an activating mutation in the gene that encodes the alpha subunit of the G protein on chromosome 20q13, activating cyclic adenylate cyclase and slowing the differentiation of osteoblasts.^3,8 

With regard to presentation, fibrous dysplasia is usually asymptomatic and discovered incidentally. The literature reports that the most common presenting symptom for patients with monostotic fibrous dysplasia of the spine is back pain localized to the lesion.¹⁵ Meredith and Healey² completed a comprehensive review of 54 cases of monostotic fibrous dysplasia involving the spine in which the majority of symptoms included back pain, neck pain, sacral region pain, pathologic fracture, painful torticollis, progressive myelopathy, paresthesias of the foot, and only 1 case of radiculopathy involving thoracic vertebra. In normal anatomy, the ureter lies within retroperitoneal fat anterior to the psoas muscle and L2-L5 transverse processes and is normally mobile.^16-18 This becomes clinically significant in lean patients as the ureter becomes closer to the spine. There are several reports of iatrogenic ureter injury in lumbar disc surgery.^16-18 Normal variants, including medialization towards the spine, may predispose the ureters to injury, iatrogenic, or otherwise. In fact, medialization of the ureters occurs commonly in black men and usually involves the right side, which may have occurred in this black patient.¹⁹

Fibrous dysplasia is most often diagnosed by its radiographic appearance or biopsy. However, recent data suggest that deoxyribonucleic acid (DNA) analysis may soon be able to diagnose this process.²⁰ Imaging typically reveals expansile, central lytic lesions within the medullary cavity. Pathology shows dense fibroblasts around immature woven bone, commonly referred to as “Chinese lettering.” The treatment varies from observation to en bloc surgical resection. Clinical observation is warranted for asymptomatic or incidental findings of monostotic fibrous dysplasia, as long as the risk for pathologic fracture is low.¹¹ Bisphosphonate therapy, both oral and intravenous, offers promising outcomes for the treatment of fibrous dysplasia, with improvement in pain and function as well as in the radiographic findings.^11,21 Management of monostotic fibrous dysplasia presenting as an isolated expansile mass of the transverse process in lumbar spine has rarely been described.^3-5 Troop and Herring⁵ reported a case of monostotic fibrous dysplasia in the lumbar spine, with involvement of the vertebral body and the posterior elements. Chow and coauthors³ and Harris and colleagues⁴ described the involvement of the transverse process of L4. Chow and coauthors’³ treatment consisted of excision that resulted in an asymptomatic patient at 8-year follow-up, while Harris and colleagues⁴ chose observation. In the latter study, the patient’s lower back pain persisted at 4-year follow-up.

Progressive enlargement, recurrence, and malignant transformation have all been described. Meredith and Healey² reported the reappearance of monostotic fibrous dysplasia affecting C2, extending through the fusion mass to involve a previously unaffected vertebra 20 years after the original C2 posterior elements excision via posterior spinal fusion from C1 to C3. In the literature, the incidence of malignant transformation ranges from 0.4% to 4%.⁸ One case of malignant transformation in thoracic spine was reported by Fu and colleagues.²² Therefore, complete removal of all affected bone is recommended.^{1,2,4,5,15,22,23}

Conclusion

We present an unusual condition with complete resolution of symptoms after surgical resection. Several points may be considered from this report. Fibrous dysplasia lesions have been found in all bones of the body, including the skull, face, and extremities; however, monostotic fibrous dysplasia involving the spine is rare.^11,23,24 Furthermore, there are no other reports of these lesions causing simultaneous nerve compression and urologic symptoms. Considering anatomy, clinicians may consider lesions of the lumbar transverse process in patients presenting to orthopedic surgeons with urinary symptoms, especially when combined with neurologic symptoms. In these lesions, fibrous dysplasia should be within the differential diagnosis. Clinicians should also recognize that complete resolution of symptoms has been reported with wide resection of these lesions.

Fibrous dysplasia is a developmental abnormality caused by excessive proliferation of immature spindle-cell fibrous tissues in bones. It is characterized by benign bony growths, which can lead to local swelling, bony deformities, and lytic conversion, predisposing the bone to pathologic fractures. Although this process can occur in cortical bone, it primarily affects the trabecular bone, leading to enlargement and expansion from within the medullary space. Malignant transformation to osteosarcoma or fibrosarcoma can occur, although this is exceedingly rare (<0.5%).^1,2

This case report describes a patient who presented with an expansile lytic mass in a lumbar transverse process that was postoperatively identified on pathology as monostotic fibrous dysplasia. Such lesions that involve the transverse processes are rare and have been associated with pain and significant discomfort.^3-5 This is the first reported case of a transverse process fibrous dysplasia causing urinary retention and neurologic symptoms simultaneously. The patient provided written informed consent for print and electronic publication of this case report.

Case Report

History

A 52-year-old black man presented to us with 6 to 8 months of increasing right flank pain, difficulty with urination, and right lower extremity pain in the area of his anterior thigh. He also complained of “buckling” of his thigh with ambulation. On review of systems, the patient denied any fevers, chills, headache, changes in weight or vision, or hearing problems. He had no systemic symptoms except for 6 months of frequent urinary tract infections and difficulty emptying his bladder, which resulted in urinary retention. He denied any significant medical history and denied any use of alcohol or tobacco.

Physical Examination

On physical examination, the patient was a well-appearing 52-year-old man in no apparent distress. No signs of gross deformity, erythema, ecchymosis, or infection were noted upon examination of his lower extremities. His motor examination was within normal limits from L2 to S1. However, both fine and gross sensation were decreased in the L3 distribution. Sensation was intact to the remaining nerve-root distributions. The Babinski sign was negative for both lower extremities, and clonus was within physiologic limits. Examination of his gait was notable for quadriceps buckling with ambulation.

Radiographic Examination

The patient initially presented to his primary care physician, who evaluated his symptoms with a computed tomography scan of his abdomen and pelvis. This showed a mass of the right L3 transverse process (Figure 1). The patient was referred to us for further management of this lesion. Dedicated magnetic resonance imaging of his lumbar spine was performed, showing an expansile, lytic, homogeneous mass in the patient’s right L3 transverse process. The mass showed a significant mass effect, compressing the exiting nerve roots and, presumably, his right ureter (Figure 2). A bone scan showed monostotic disease. The patient had failed conservative management, including physical therapy and anti-inflammatory medications. His right-sided radiculopathy was worsening, and he complained that the pain was affecting his quality of life and limiting his performance of his daily activities. A pain management specialist was requested to better manage his pain. Considering progression of his condition, surgical management was discussed, leading to a planned biopsy and resection of the mass.

Surgical Procedure

The patient was taken into the operating room and positioned prone on a Jackson table with a Wilson frame. Fluoroscopy was used to localize the right L3 transverse process. An incision was made over the right L3 transverse process and a Wiltse intramuscular approach was performed. After the right L3 transverse process was identified, the soft tissue from the transverse process was retracted in all directions, including medially up to the pedicle. The intertransverse ligament was detached from both the cephalad and caudal edges of the transverse process. We used a Woodson elevator to perform subperiosteal dissection to remove the soft tissue circumferentially. After dissection, we placed a Cobb elevator to protect the rostral and caudal soft tissue and used a high-speed burr to amputate the lytic transverse process at its base. The transverse process was removed en bloc (Figure 3) and sent for frozen pathologic evaluation (Figure 4). After the diagnosis of a benign lesion, the wound was closed in layers.

Complete resolution of both urinary and neurologic symptoms were immediately noted and up to 1 month postoperatively.

Discussion

Primary bone tumors of the spine are rare, with a reported incidence of 2.5 to 8.5 per 100,000 people per year.⁶ The estimated incidence of benign primary tumors involving the spine accounts for about 1% of all primary skeletal tumors and nearly 5% for malignant tumors.^7-9 In contrast, secondary tumors involving the bony spinal column are relatively common. Postmortem studies indicate up to 70% of cancer patients demonstrate axial skeletal involvement.^10,11 The most commonly encountered benign tumors affecting the spine include giant cell tumors, osteoid osteomas, osteoblastomas, and hemangiomas. Chordomas are frequently reported as the most common malignant primary spine neoplasms. Of all primary benign bone lesions, fibrous dysplasia accounts for approximately 1.4%.⁸

Primary and secondary malignant osseous tumors have a predilection for the anterior column, and primary benign lesions usually affect the posterior column.^8,12-14 Because of the greater blood supply and more direct communication with the viscera via the Batson plexus, the anterior column is most likely to be seeded by metastatic disease. Similarly, hemangiomas and multiple myeloma are typically located in the anterior column, most likely because of the more abundant blood supply there. Chordomas are also found in this cancellous anterior column. Osteoid osteoma, osteoblastoma, and aneurysmal bone cysts are found within the more cortical architecture of posterior elements. The location of this patient’s lesion within the transverse process elevates confidence in the diagnosis of a benign lesion.

The conventional, isolated form of fibrous dysplasia was originally described in 1942 by Lichtenstein and Jaffe.² They described 15 cases of benign “nonosteogenic fibromas” near the ends of long bones in young patients. Monostotic fibrous dysplasia constitutes the majority of these cases, approximately 80%.^1,2,8,15 Fibrous dysplasia may also present as part of McCune-Albright syndrome, in which case it is associated with precocious puberty and café au lait spots. Less commonly, they are associated with intramuscular myxomas, as in Mazabraud syndrome. The lesions in these syndromes are typically polyostotic. In all forms, fibrous dysplasia develops from an activating mutation in the gene that encodes the alpha subunit of the G protein on chromosome 20q13, activating cyclic adenylate cyclase and slowing the differentiation of osteoblasts.^3,8 

With regard to presentation, fibrous dysplasia is usually asymptomatic and discovered incidentally. The literature reports that the most common presenting symptom for patients with monostotic fibrous dysplasia of the spine is back pain localized to the lesion.¹⁵ Meredith and Healey² completed a comprehensive review of 54 cases of monostotic fibrous dysplasia involving the spine in which the majority of symptoms included back pain, neck pain, sacral region pain, pathologic fracture, painful torticollis, progressive myelopathy, paresthesias of the foot, and only 1 case of radiculopathy involving thoracic vertebra. In normal anatomy, the ureter lies within retroperitoneal fat anterior to the psoas muscle and L2-L5 transverse processes and is normally mobile.^16-18 This becomes clinically significant in lean patients as the ureter becomes closer to the spine. There are several reports of iatrogenic ureter injury in lumbar disc surgery.^16-18 Normal variants, including medialization towards the spine, may predispose the ureters to injury, iatrogenic, or otherwise. In fact, medialization of the ureters occurs commonly in black men and usually involves the right side, which may have occurred in this black patient.¹⁹

Fibrous dysplasia is most often diagnosed by its radiographic appearance or biopsy. However, recent data suggest that deoxyribonucleic acid (DNA) analysis may soon be able to diagnose this process.²⁰ Imaging typically reveals expansile, central lytic lesions within the medullary cavity. Pathology shows dense fibroblasts around immature woven bone, commonly referred to as “Chinese lettering.” The treatment varies from observation to en bloc surgical resection. Clinical observation is warranted for asymptomatic or incidental findings of monostotic fibrous dysplasia, as long as the risk for pathologic fracture is low.¹¹ Bisphosphonate therapy, both oral and intravenous, offers promising outcomes for the treatment of fibrous dysplasia, with improvement in pain and function as well as in the radiographic findings.^11,21 Management of monostotic fibrous dysplasia presenting as an isolated expansile mass of the transverse process in lumbar spine has rarely been described.^3-5 Troop and Herring⁵ reported a case of monostotic fibrous dysplasia in the lumbar spine, with involvement of the vertebral body and the posterior elements. Chow and coauthors³ and Harris and colleagues⁴ described the involvement of the transverse process of L4. Chow and coauthors’³ treatment consisted of excision that resulted in an asymptomatic patient at 8-year follow-up, while Harris and colleagues⁴ chose observation. In the latter study, the patient’s lower back pain persisted at 4-year follow-up.

Progressive enlargement, recurrence, and malignant transformation have all been described. Meredith and Healey² reported the reappearance of monostotic fibrous dysplasia affecting C2, extending through the fusion mass to involve a previously unaffected vertebra 20 years after the original C2 posterior elements excision via posterior spinal fusion from C1 to C3. In the literature, the incidence of malignant transformation ranges from 0.4% to 4%.⁸ One case of malignant transformation in thoracic spine was reported by Fu and colleagues.²² Therefore, complete removal of all affected bone is recommended.^{1,2,4,5,15,22,23}

Conclusion

We present an unusual condition with complete resolution of symptoms after surgical resection. Several points may be considered from this report. Fibrous dysplasia lesions have been found in all bones of the body, including the skull, face, and extremities; however, monostotic fibrous dysplasia involving the spine is rare.^11,23,24 Furthermore, there are no other reports of these lesions causing simultaneous nerve compression and urologic symptoms. Considering anatomy, clinicians may consider lesions of the lumbar transverse process in patients presenting to orthopedic surgeons with urinary symptoms, especially when combined with neurologic symptoms. In these lesions, fibrous dysplasia should be within the differential diagnosis. Clinicians should also recognize that complete resolution of symptoms has been reported with wide resection of these lesions.

Fibrous dysplasia is a developmental abnormality caused by excessive proliferation of immature spindle-cell fibrous tissues in bones. It is characterized by benign bony growths, which can lead to local swelling, bony deformities, and lytic conversion, predisposing the bone to pathologic fractures. Although this process can occur in cortical bone, it primarily affects the trabecular bone, leading to enlargement and expansion from within the medullary space. Malignant transformation to osteosarcoma or fibrosarcoma can occur, although this is exceedingly rare (<0.5%).^1,2

This case report describes a patient who presented with an expansile lytic mass in a lumbar transverse process that was postoperatively identified on pathology as monostotic fibrous dysplasia. Such lesions that involve the transverse processes are rare and have been associated with pain and significant discomfort.^3-5 This is the first reported case of a transverse process fibrous dysplasia causing urinary retention and neurologic symptoms simultaneously. The patient provided written informed consent for print and electronic publication of this case report.

Case Report

History

A 52-year-old black man presented to us with 6 to 8 months of increasing right flank pain, difficulty with urination, and right lower extremity pain in the area of his anterior thigh. He also complained of “buckling” of his thigh with ambulation. On review of systems, the patient denied any fevers, chills, headache, changes in weight or vision, or hearing problems. He had no systemic symptoms except for 6 months of frequent urinary tract infections and difficulty emptying his bladder, which resulted in urinary retention. He denied any significant medical history and denied any use of alcohol or tobacco.

Physical Examination

On physical examination, the patient was a well-appearing 52-year-old man in no apparent distress. No signs of gross deformity, erythema, ecchymosis, or infection were noted upon examination of his lower extremities. His motor examination was within normal limits from L2 to S1. However, both fine and gross sensation were decreased in the L3 distribution. Sensation was intact to the remaining nerve-root distributions. The Babinski sign was negative for both lower extremities, and clonus was within physiologic limits. Examination of his gait was notable for quadriceps buckling with ambulation.

Radiographic Examination

The patient initially presented to his primary care physician, who evaluated his symptoms with a computed tomography scan of his abdomen and pelvis. This showed a mass of the right L3 transverse process (Figure 1). The patient was referred to us for further management of this lesion. Dedicated magnetic resonance imaging of his lumbar spine was performed, showing an expansile, lytic, homogeneous mass in the patient’s right L3 transverse process. The mass showed a significant mass effect, compressing the exiting nerve roots and, presumably, his right ureter (Figure 2). A bone scan showed monostotic disease. The patient had failed conservative management, including physical therapy and anti-inflammatory medications. His right-sided radiculopathy was worsening, and he complained that the pain was affecting his quality of life and limiting his performance of his daily activities. A pain management specialist was requested to better manage his pain. Considering progression of his condition, surgical management was discussed, leading to a planned biopsy and resection of the mass.

Surgical Procedure

The patient was taken into the operating room and positioned prone on a Jackson table with a Wilson frame. Fluoroscopy was used to localize the right L3 transverse process. An incision was made over the right L3 transverse process and a Wiltse intramuscular approach was performed. After the right L3 transverse process was identified, the soft tissue from the transverse process was retracted in all directions, including medially up to the pedicle. The intertransverse ligament was detached from both the cephalad and caudal edges of the transverse process. We used a Woodson elevator to perform subperiosteal dissection to remove the soft tissue circumferentially. After dissection, we placed a Cobb elevator to protect the rostral and caudal soft tissue and used a high-speed burr to amputate the lytic transverse process at its base. The transverse process was removed en bloc (Figure 3) and sent for frozen pathologic evaluation (Figure 4). After the diagnosis of a benign lesion, the wound was closed in layers.

Complete resolution of both urinary and neurologic symptoms were immediately noted and up to 1 month postoperatively.

Discussion

Primary bone tumors of the spine are rare, with a reported incidence of 2.5 to 8.5 per 100,000 people per year.⁶ The estimated incidence of benign primary tumors involving the spine accounts for about 1% of all primary skeletal tumors and nearly 5% for malignant tumors.^7-9 In contrast, secondary tumors involving the bony spinal column are relatively common. Postmortem studies indicate up to 70% of cancer patients demonstrate axial skeletal involvement.^10,11 The most commonly encountered benign tumors affecting the spine include giant cell tumors, osteoid osteomas, osteoblastomas, and hemangiomas. Chordomas are frequently reported as the most common malignant primary spine neoplasms. Of all primary benign bone lesions, fibrous dysplasia accounts for approximately 1.4%.⁸

Primary and secondary malignant osseous tumors have a predilection for the anterior column, and primary benign lesions usually affect the posterior column.^8,12-14 Because of the greater blood supply and more direct communication with the viscera via the Batson plexus, the anterior column is most likely to be seeded by metastatic disease. Similarly, hemangiomas and multiple myeloma are typically located in the anterior column, most likely because of the more abundant blood supply there. Chordomas are also found in this cancellous anterior column. Osteoid osteoma, osteoblastoma, and aneurysmal bone cysts are found within the more cortical architecture of posterior elements. The location of this patient’s lesion within the transverse process elevates confidence in the diagnosis of a benign lesion.

The conventional, isolated form of fibrous dysplasia was originally described in 1942 by Lichtenstein and Jaffe.² They described 15 cases of benign “nonosteogenic fibromas” near the ends of long bones in young patients. Monostotic fibrous dysplasia constitutes the majority of these cases, approximately 80%.^1,2,8,15 Fibrous dysplasia may also present as part of McCune-Albright syndrome, in which case it is associated with precocious puberty and café au lait spots. Less commonly, they are associated with intramuscular myxomas, as in Mazabraud syndrome. The lesions in these syndromes are typically polyostotic. In all forms, fibrous dysplasia develops from an activating mutation in the gene that encodes the alpha subunit of the G protein on chromosome 20q13, activating cyclic adenylate cyclase and slowing the differentiation of osteoblasts.^3,8 

With regard to presentation, fibrous dysplasia is usually asymptomatic and discovered incidentally. The literature reports that the most common presenting symptom for patients with monostotic fibrous dysplasia of the spine is back pain localized to the lesion.¹⁵ Meredith and Healey² completed a comprehensive review of 54 cases of monostotic fibrous dysplasia involving the spine in which the majority of symptoms included back pain, neck pain, sacral region pain, pathologic fracture, painful torticollis, progressive myelopathy, paresthesias of the foot, and only 1 case of radiculopathy involving thoracic vertebra. In normal anatomy, the ureter lies within retroperitoneal fat anterior to the psoas muscle and L2-L5 transverse processes and is normally mobile.^16-18 This becomes clinically significant in lean patients as the ureter becomes closer to the spine. There are several reports of iatrogenic ureter injury in lumbar disc surgery.^16-18 Normal variants, including medialization towards the spine, may predispose the ureters to injury, iatrogenic, or otherwise. In fact, medialization of the ureters occurs commonly in black men and usually involves the right side, which may have occurred in this black patient.¹⁹

Fibrous dysplasia is most often diagnosed by its radiographic appearance or biopsy. However, recent data suggest that deoxyribonucleic acid (DNA) analysis may soon be able to diagnose this process.²⁰ Imaging typically reveals expansile, central lytic lesions within the medullary cavity. Pathology shows dense fibroblasts around immature woven bone, commonly referred to as “Chinese lettering.” The treatment varies from observation to en bloc surgical resection. Clinical observation is warranted for asymptomatic or incidental findings of monostotic fibrous dysplasia, as long as the risk for pathologic fracture is low.¹¹ Bisphosphonate therapy, both oral and intravenous, offers promising outcomes for the treatment of fibrous dysplasia, with improvement in pain and function as well as in the radiographic findings.^11,21 Management of monostotic fibrous dysplasia presenting as an isolated expansile mass of the transverse process in lumbar spine has rarely been described.^3-5 Troop and Herring⁵ reported a case of monostotic fibrous dysplasia in the lumbar spine, with involvement of the vertebral body and the posterior elements. Chow and coauthors³ and Harris and colleagues⁴ described the involvement of the transverse process of L4. Chow and coauthors’³ treatment consisted of excision that resulted in an asymptomatic patient at 8-year follow-up, while Harris and colleagues⁴ chose observation. In the latter study, the patient’s lower back pain persisted at 4-year follow-up.

Progressive enlargement, recurrence, and malignant transformation have all been described. Meredith and Healey² reported the reappearance of monostotic fibrous dysplasia affecting C2, extending through the fusion mass to involve a previously unaffected vertebra 20 years after the original C2 posterior elements excision via posterior spinal fusion from C1 to C3. In the literature, the incidence of malignant transformation ranges from 0.4% to 4%.⁸ One case of malignant transformation in thoracic spine was reported by Fu and colleagues.²² Therefore, complete removal of all affected bone is recommended.^{1,2,4,5,15,22,23}

Conclusion

We present an unusual condition with complete resolution of symptoms after surgical resection. Several points may be considered from this report. Fibrous dysplasia lesions have been found in all bones of the body, including the skull, face, and extremities; however, monostotic fibrous dysplasia involving the spine is rare.^11,23,24 Furthermore, there are no other reports of these lesions causing simultaneous nerve compression and urologic symptoms. Considering anatomy, clinicians may consider lesions of the lumbar transverse process in patients presenting to orthopedic surgeons with urinary symptoms, especially when combined with neurologic symptoms. In these lesions, fibrous dysplasia should be within the differential diagnosis. Clinicians should also recognize that complete resolution of symptoms has been reported with wide resection of these lesions.