Article

To the Editor:

Calcinosis cutis is a condition characterized by the deposition of insoluble calcium salts in the skin. Dystrophic calcinosis cutis is the most common type, occurring in previously traumatized skin in the absence of abnormal blood calcium levels. It commonly is seen in patients with connective tissue diseases and is thought to be precipitated by chronic inflammation and vascular hypoxia.¹ Herein, we describe a case of calcinosis cutis arising after treatment with subcutaneous glatiramer acetate, an agent that is effective for the treatment of relapsing-remitting multiple sclerosis (MS). Diagnostic workup and treatment modalities for calcinosis cutis in this patient population should be considered in the context of minimizing interruption or discontinuation of this disease-modifying agent.

A 53-year-old woman with a history of relapsing-remitting MS and systemic lupus erythematosus (SLE) presented with multiple firm asymptomatic subcutaneous nodules on the thighs of 1 year’s duration that were increasing in number. The involved areas were the injection sites of subcutaneous glatiramer acetate, an immunomodulator for the treatment of MS, which our patient self-administered 3 times weekly. Physical examination revealed multiple flesh-colored to white, firm, and nontender nodules on the thighs (Figure). There was no epidermal change, and she had no other skin involvement. A punch biopsy of one of the nodules revealed calcium deposits in collagen bundles of the deep dermis. Calcium, phosphorus, parathyroid hormone, and vitamin D levels were within reference range. She declined further treatment for the calcinosis cutis and opted to continue treatment with glatiramer acetate, as her MS was well controlled on this medication.

Glatiramer acetate is an immunogenic polypeptide injectable that is approved by the US Food and Drug Administration for the treatment of relapsing-remitting MS.² It is composed of synthetic polypeptides and contains 4 naturally occurring amino acids. Glatiramer acetate is administered subcutaneously as 20 mg/mL/d or 40 mg/mL 3 times weekly. Transient injection-site reactions are the most common cutaneous adverse events and include localized edema, induration, erythema, pain, and pruritus.³ There have been multiple reports of lobular panniculitis and skin necrosis as well as embolia cutis medicamentosa (Nicolau syndrome).^4,5 Our case of calcinosis cutis related to glatiramer acetate is unique. The mechanism of calcinosis cutis in our patient likely was dystrophic due to tissue damage, rather than due to the injection of a calcium-containing substance. Our patient’s history of SLE is a notable risk factor for the development of calcinosis cutis, likely incited by the trauma occurring with subcutaneous injections.⁶

The mainstay of treatment for localized calcinosis cutis in the setting of connective tissue disease is surgical excision as well as treatment of the underlying disorder. Potential therapies include calcium channel blockers, warfarin, bisphosphonates, intravenous immunoglobulin, minocycline, colchicine, anti–tumor necrosis factor agents, intralesional corticosteroids, intravenous sodium thiosulfate, and CO₂ laser.^1,6 Our patient was already on intravenous immunoglobulin for MS and hydroxychloroquine for SLE. In select cases where the patient is asymptomatic and prefers not to pursue treatment, no treatment is necessary.

Although calcinosis cutis may occur in SLE alone, it is uncommon and usually is seen in chronic severe SLE, where calcification usually occurs in the setting of pre-existing cutaneous lupus.⁴ This case report of calcinosis cutis following treatment with glatiramer acetate highlights some of the cutaneous side effects associated with glatiramer acetate injections and should prompt practitioners to consider dystrophic calcinosis cutis in patients requiring subcutaneous medications, particularly in those with pre-existing connective tissue disease.

To the Editor:

Calcinosis cutis is a condition characterized by the deposition of insoluble calcium salts in the skin. Dystrophic calcinosis cutis is the most common type, occurring in previously traumatized skin in the absence of abnormal blood calcium levels. It commonly is seen in patients with connective tissue diseases and is thought to be precipitated by chronic inflammation and vascular hypoxia.¹ Herein, we describe a case of calcinosis cutis arising after treatment with subcutaneous glatiramer acetate, an agent that is effective for the treatment of relapsing-remitting multiple sclerosis (MS). Diagnostic workup and treatment modalities for calcinosis cutis in this patient population should be considered in the context of minimizing interruption or discontinuation of this disease-modifying agent.

A 53-year-old woman with a history of relapsing-remitting MS and systemic lupus erythematosus (SLE) presented with multiple firm asymptomatic subcutaneous nodules on the thighs of 1 year’s duration that were increasing in number. The involved areas were the injection sites of subcutaneous glatiramer acetate, an immunomodulator for the treatment of MS, which our patient self-administered 3 times weekly. Physical examination revealed multiple flesh-colored to white, firm, and nontender nodules on the thighs (Figure). There was no epidermal change, and she had no other skin involvement. A punch biopsy of one of the nodules revealed calcium deposits in collagen bundles of the deep dermis. Calcium, phosphorus, parathyroid hormone, and vitamin D levels were within reference range. She declined further treatment for the calcinosis cutis and opted to continue treatment with glatiramer acetate, as her MS was well controlled on this medication.

Glatiramer acetate is an immunogenic polypeptide injectable that is approved by the US Food and Drug Administration for the treatment of relapsing-remitting MS.² It is composed of synthetic polypeptides and contains 4 naturally occurring amino acids. Glatiramer acetate is administered subcutaneously as 20 mg/mL/d or 40 mg/mL 3 times weekly. Transient injection-site reactions are the most common cutaneous adverse events and include localized edema, induration, erythema, pain, and pruritus.³ There have been multiple reports of lobular panniculitis and skin necrosis as well as embolia cutis medicamentosa (Nicolau syndrome).^4,5 Our case of calcinosis cutis related to glatiramer acetate is unique. The mechanism of calcinosis cutis in our patient likely was dystrophic due to tissue damage, rather than due to the injection of a calcium-containing substance. Our patient’s history of SLE is a notable risk factor for the development of calcinosis cutis, likely incited by the trauma occurring with subcutaneous injections.⁶

The mainstay of treatment for localized calcinosis cutis in the setting of connective tissue disease is surgical excision as well as treatment of the underlying disorder. Potential therapies include calcium channel blockers, warfarin, bisphosphonates, intravenous immunoglobulin, minocycline, colchicine, anti–tumor necrosis factor agents, intralesional corticosteroids, intravenous sodium thiosulfate, and CO₂ laser.^1,6 Our patient was already on intravenous immunoglobulin for MS and hydroxychloroquine for SLE. In select cases where the patient is asymptomatic and prefers not to pursue treatment, no treatment is necessary.

Although calcinosis cutis may occur in SLE alone, it is uncommon and usually is seen in chronic severe SLE, where calcification usually occurs in the setting of pre-existing cutaneous lupus.⁴ This case report of calcinosis cutis following treatment with glatiramer acetate highlights some of the cutaneous side effects associated with glatiramer acetate injections and should prompt practitioners to consider dystrophic calcinosis cutis in patients requiring subcutaneous medications, particularly in those with pre-existing connective tissue disease.

To the Editor:

Calcinosis cutis is a condition characterized by the deposition of insoluble calcium salts in the skin. Dystrophic calcinosis cutis is the most common type, occurring in previously traumatized skin in the absence of abnormal blood calcium levels. It commonly is seen in patients with connective tissue diseases and is thought to be precipitated by chronic inflammation and vascular hypoxia.¹ Herein, we describe a case of calcinosis cutis arising after treatment with subcutaneous glatiramer acetate, an agent that is effective for the treatment of relapsing-remitting multiple sclerosis (MS). Diagnostic workup and treatment modalities for calcinosis cutis in this patient population should be considered in the context of minimizing interruption or discontinuation of this disease-modifying agent.

A 53-year-old woman with a history of relapsing-remitting MS and systemic lupus erythematosus (SLE) presented with multiple firm asymptomatic subcutaneous nodules on the thighs of 1 year’s duration that were increasing in number. The involved areas were the injection sites of subcutaneous glatiramer acetate, an immunomodulator for the treatment of MS, which our patient self-administered 3 times weekly. Physical examination revealed multiple flesh-colored to white, firm, and nontender nodules on the thighs (Figure). There was no epidermal change, and she had no other skin involvement. A punch biopsy of one of the nodules revealed calcium deposits in collagen bundles of the deep dermis. Calcium, phosphorus, parathyroid hormone, and vitamin D levels were within reference range. She declined further treatment for the calcinosis cutis and opted to continue treatment with glatiramer acetate, as her MS was well controlled on this medication.

Glatiramer acetate is an immunogenic polypeptide injectable that is approved by the US Food and Drug Administration for the treatment of relapsing-remitting MS.² It is composed of synthetic polypeptides and contains 4 naturally occurring amino acids. Glatiramer acetate is administered subcutaneously as 20 mg/mL/d or 40 mg/mL 3 times weekly. Transient injection-site reactions are the most common cutaneous adverse events and include localized edema, induration, erythema, pain, and pruritus.³ There have been multiple reports of lobular panniculitis and skin necrosis as well as embolia cutis medicamentosa (Nicolau syndrome).^4,5 Our case of calcinosis cutis related to glatiramer acetate is unique. The mechanism of calcinosis cutis in our patient likely was dystrophic due to tissue damage, rather than due to the injection of a calcium-containing substance. Our patient’s history of SLE is a notable risk factor for the development of calcinosis cutis, likely incited by the trauma occurring with subcutaneous injections.⁶

The mainstay of treatment for localized calcinosis cutis in the setting of connective tissue disease is surgical excision as well as treatment of the underlying disorder. Potential therapies include calcium channel blockers, warfarin, bisphosphonates, intravenous immunoglobulin, minocycline, colchicine, anti–tumor necrosis factor agents, intralesional corticosteroids, intravenous sodium thiosulfate, and CO₂ laser.^1,6 Our patient was already on intravenous immunoglobulin for MS and hydroxychloroquine for SLE. In select cases where the patient is asymptomatic and prefers not to pursue treatment, no treatment is necessary.

Although calcinosis cutis may occur in SLE alone, it is uncommon and usually is seen in chronic severe SLE, where calcification usually occurs in the setting of pre-existing cutaneous lupus.⁴ This case report of calcinosis cutis following treatment with glatiramer acetate highlights some of the cutaneous side effects associated with glatiramer acetate injections and should prompt practitioners to consider dystrophic calcinosis cutis in patients requiring subcutaneous medications, particularly in those with pre-existing connective tissue disease.

To the Editor:

Bullous pemphigoid (BP) is an autoimmune blistering disease characterized by the formation of antihemidesmosomal antibodies, resulting in tense bullae concentrated on the extremities and trunk that often are preceded by a pruritic urticarial phase.¹ A rare complication of BP is the subsequent development of acquired hemophilia A. We report a case of BP with associated factor VIII–neutralizing antibodies in a patient who improved with prednisone and rituximab therapy.

A 78-year-old woman presented with red-orange pruritic plaques on the right heel that spread to involve the arms and legs, abdomen, and trunk with new-onset bullae over the course of 2 weeks (Figure 1). Dermatology was consulted, and a diagnosis of BP was confirmed via biopsy and direct immunofluorescence.

Despite treatment with prednisone 40 mg/d and clobetasol ointment 0.05%, she continued to develop extensive cutaneous bullae and new hemorrhagic bullae on the buccal mucosae (Figure 2), necessitating hospital admission. She clinically improved after prednisone was increased to 60 mg/d and mycophenolate mofetil 500 mg twice daily was added; however, she returned 8 days after discharge from the hospital with altered mental status, new-onset hematomas of the abdomen and right leg, and a hemoglobin level of 5.8 g/dL (reference range, 14.0–17.5 g/dL). Activated prothrombin time was prolonged without correction on mixing studies, raising concern for coagulation factor inhibition. Factor VIII activity was diminished to 9% and then 1% three days later. Mycophenolate mofetil was discontinued, and the patient was acutely stabilized with blood transfusions, intravenous immunoglobulin, tranexamic acid, and aminocaproic acid. Rituximab was initiated at 1000 mg and then administered again 2 weeks later. At 7-week follow-up, coagulation studies normalized, and there was no evidence of blistering dermatosis on examination.

Bullous pemphigoid generally is seen in patients older than 60 years, and the incidence increases with age. The disease course follows formation of IgG antibodies against BP180 or BP230, leading to localized activation of the complement cascade at the basement membrane zone.¹ Medications, vaccinations, UV radiation, and burns have been implicated in disease induction.²

Identification of antihemidesmosomal antibodies on lesional biopsy via direct immunofluorescence is the gold standard for diagnosis, though indirect antibodies measured via enzyme-linked immunosorbent assay may provide information regarding disease severity.¹ Patients with milder disease may be treated with topical corticosteroids, doxycycline, and nicotinamide; however, severe disease requires treatment with systemic glucocorticoids and steroid-sparing agents.³ Rituximab initially was approved by the US Food and Drug Administration for the treatment of pemphigus vulgaris, and mounting evidence for the use of rituximab in BP is promising. Although data are limited to retrospective studies, rituximab has shown notable remission rates and steroid-sparing effects in those with moderate to severe BP.⁴

Acquired hemophilia A (AHA) is caused by the production of IgG autoantibodies, which block physiologic interactions between factor VIII and factor IX, phospholipids, and von Willebrand factor.⁵ Acquired hemophilia A often is diagnosed by prolonged activated prothrombin time and decreased factor VIII activity after a previously unaffected patient develops severe bleeding. Treatment involves re-establishing hemostasis and the use of corticosteroids and immunosuppressive agents to diminish autoantibody production.⁴

Bullous pemphigoid–associated AHA likely is due to antigenic similarity between BP180 and factor VIII, leading to concomitant neutralization of factor VIII with the production of BP-associated autoantibodies.⁵ Bullous pemphigoid–associated AHA has been reported with manifestations of bleeding concurrent with or after the development of dermatologic disease. Rituximab use has been reported with clinical efficacy in several cases, including our patient.⁶ Continued hematologic monitoring is recommended, as recurrences are common within the first 2 years.⁵

To the Editor:

Bullous pemphigoid (BP) is an autoimmune blistering disease characterized by the formation of antihemidesmosomal antibodies, resulting in tense bullae concentrated on the extremities and trunk that often are preceded by a pruritic urticarial phase.¹ A rare complication of BP is the subsequent development of acquired hemophilia A. We report a case of BP with associated factor VIII–neutralizing antibodies in a patient who improved with prednisone and rituximab therapy.

A 78-year-old woman presented with red-orange pruritic plaques on the right heel that spread to involve the arms and legs, abdomen, and trunk with new-onset bullae over the course of 2 weeks (Figure 1). Dermatology was consulted, and a diagnosis of BP was confirmed via biopsy and direct immunofluorescence.

Despite treatment with prednisone 40 mg/d and clobetasol ointment 0.05%, she continued to develop extensive cutaneous bullae and new hemorrhagic bullae on the buccal mucosae (Figure 2), necessitating hospital admission. She clinically improved after prednisone was increased to 60 mg/d and mycophenolate mofetil 500 mg twice daily was added; however, she returned 8 days after discharge from the hospital with altered mental status, new-onset hematomas of the abdomen and right leg, and a hemoglobin level of 5.8 g/dL (reference range, 14.0–17.5 g/dL). Activated prothrombin time was prolonged without correction on mixing studies, raising concern for coagulation factor inhibition. Factor VIII activity was diminished to 9% and then 1% three days later. Mycophenolate mofetil was discontinued, and the patient was acutely stabilized with blood transfusions, intravenous immunoglobulin, tranexamic acid, and aminocaproic acid. Rituximab was initiated at 1000 mg and then administered again 2 weeks later. At 7-week follow-up, coagulation studies normalized, and there was no evidence of blistering dermatosis on examination.

Bullous pemphigoid generally is seen in patients older than 60 years, and the incidence increases with age. The disease course follows formation of IgG antibodies against BP180 or BP230, leading to localized activation of the complement cascade at the basement membrane zone.¹ Medications, vaccinations, UV radiation, and burns have been implicated in disease induction.²

Identification of antihemidesmosomal antibodies on lesional biopsy via direct immunofluorescence is the gold standard for diagnosis, though indirect antibodies measured via enzyme-linked immunosorbent assay may provide information regarding disease severity.¹ Patients with milder disease may be treated with topical corticosteroids, doxycycline, and nicotinamide; however, severe disease requires treatment with systemic glucocorticoids and steroid-sparing agents.³ Rituximab initially was approved by the US Food and Drug Administration for the treatment of pemphigus vulgaris, and mounting evidence for the use of rituximab in BP is promising. Although data are limited to retrospective studies, rituximab has shown notable remission rates and steroid-sparing effects in those with moderate to severe BP.⁴

Acquired hemophilia A (AHA) is caused by the production of IgG autoantibodies, which block physiologic interactions between factor VIII and factor IX, phospholipids, and von Willebrand factor.⁵ Acquired hemophilia A often is diagnosed by prolonged activated prothrombin time and decreased factor VIII activity after a previously unaffected patient develops severe bleeding. Treatment involves re-establishing hemostasis and the use of corticosteroids and immunosuppressive agents to diminish autoantibody production.⁴

Bullous pemphigoid–associated AHA likely is due to antigenic similarity between BP180 and factor VIII, leading to concomitant neutralization of factor VIII with the production of BP-associated autoantibodies.⁵ Bullous pemphigoid–associated AHA has been reported with manifestations of bleeding concurrent with or after the development of dermatologic disease. Rituximab use has been reported with clinical efficacy in several cases, including our patient.⁶ Continued hematologic monitoring is recommended, as recurrences are common within the first 2 years.⁵

To the Editor:

Bullous pemphigoid (BP) is an autoimmune blistering disease characterized by the formation of antihemidesmosomal antibodies, resulting in tense bullae concentrated on the extremities and trunk that often are preceded by a pruritic urticarial phase.¹ A rare complication of BP is the subsequent development of acquired hemophilia A. We report a case of BP with associated factor VIII–neutralizing antibodies in a patient who improved with prednisone and rituximab therapy.

A 78-year-old woman presented with red-orange pruritic plaques on the right heel that spread to involve the arms and legs, abdomen, and trunk with new-onset bullae over the course of 2 weeks (Figure 1). Dermatology was consulted, and a diagnosis of BP was confirmed via biopsy and direct immunofluorescence.

Despite treatment with prednisone 40 mg/d and clobetasol ointment 0.05%, she continued to develop extensive cutaneous bullae and new hemorrhagic bullae on the buccal mucosae (Figure 2), necessitating hospital admission. She clinically improved after prednisone was increased to 60 mg/d and mycophenolate mofetil 500 mg twice daily was added; however, she returned 8 days after discharge from the hospital with altered mental status, new-onset hematomas of the abdomen and right leg, and a hemoglobin level of 5.8 g/dL (reference range, 14.0–17.5 g/dL). Activated prothrombin time was prolonged without correction on mixing studies, raising concern for coagulation factor inhibition. Factor VIII activity was diminished to 9% and then 1% three days later. Mycophenolate mofetil was discontinued, and the patient was acutely stabilized with blood transfusions, intravenous immunoglobulin, tranexamic acid, and aminocaproic acid. Rituximab was initiated at 1000 mg and then administered again 2 weeks later. At 7-week follow-up, coagulation studies normalized, and there was no evidence of blistering dermatosis on examination.

Bullous pemphigoid generally is seen in patients older than 60 years, and the incidence increases with age. The disease course follows formation of IgG antibodies against BP180 or BP230, leading to localized activation of the complement cascade at the basement membrane zone.¹ Medications, vaccinations, UV radiation, and burns have been implicated in disease induction.²

Identification of antihemidesmosomal antibodies on lesional biopsy via direct immunofluorescence is the gold standard for diagnosis, though indirect antibodies measured via enzyme-linked immunosorbent assay may provide information regarding disease severity.¹ Patients with milder disease may be treated with topical corticosteroids, doxycycline, and nicotinamide; however, severe disease requires treatment with systemic glucocorticoids and steroid-sparing agents.³ Rituximab initially was approved by the US Food and Drug Administration for the treatment of pemphigus vulgaris, and mounting evidence for the use of rituximab in BP is promising. Although data are limited to retrospective studies, rituximab has shown notable remission rates and steroid-sparing effects in those with moderate to severe BP.⁴

Acquired hemophilia A (AHA) is caused by the production of IgG autoantibodies, which block physiologic interactions between factor VIII and factor IX, phospholipids, and von Willebrand factor.⁵ Acquired hemophilia A often is diagnosed by prolonged activated prothrombin time and decreased factor VIII activity after a previously unaffected patient develops severe bleeding. Treatment involves re-establishing hemostasis and the use of corticosteroids and immunosuppressive agents to diminish autoantibody production.⁴

Bullous pemphigoid–associated AHA likely is due to antigenic similarity between BP180 and factor VIII, leading to concomitant neutralization of factor VIII with the production of BP-associated autoantibodies.⁵ Bullous pemphigoid–associated AHA has been reported with manifestations of bleeding concurrent with or after the development of dermatologic disease. Rituximab use has been reported with clinical efficacy in several cases, including our patient.⁶ Continued hematologic monitoring is recommended, as recurrences are common within the first 2 years.⁵

To the Editor:

Peristomal pyoderma gangrenosum (PPG) is a rare entity first described in 1984.¹ Lesions usually begin as pustules that coalesce into an erythematous skin ulceration that contains purulent material. The lesion appears on the skin that surrounds an abdominal stoma. Peristomal pyoderma gangrenosum typically is associated with Crohn disease and ulcerative colitis, cancer, blood dyscrasia, diabetes mellitus, and hepatitis.² We describe a case of PPG following an ileostomy in a patient with colon cancer and a related history of Crohn disease.

A 32-year-old woman presented to a dermatology office with a spontaneously painful, 3.2-cm ulceration that was extremely tender to palpation, located immediately adjacent to the site of an ileostomy (Figure). The patient had a history of refractory constipation that failed to respond to standard conservative measures 4 years prior. She underwent a colonoscopy, which revealed a 6.5-cm, irregularly shaped, exophytic mass in the rectosigmoid portion of the colon. Histopathologic examination of several biopsies confirmed the diagnosis of moderately well-differentiated adenocarcinoma, and additional evaluation determined the cancer to be stage IIB. She had a medical history of pancolonic Crohn disease since high school that was treated with periodic infusions of infliximab at the standard dose of 5 mg/kg. Colon cancer treatment consisted of preoperative radiotherapy, complete colectomy with ileoanal anastomosis, and creation of a J-pouch and formation of a temporary ileostomy, along with postoperative capecitabine chemotherapy.

The ileostomy eventually was reversed, and the patient did well for 3 years. When the patient developed severe abdominal pain, the J-pouch was examined and found to be remarkably involved with Crohn disease. However, during the colonoscopy, the J-pouch was inadvertently punctured, leading to the formation of a large pelvic abscess. The latter necessitated diversion of stool, and the patient had the original ileostomy recreated.

Prior to presentation to dermatology, various consultants suspected the ulceration was possibly a deep fungal infection, cutaneous Crohn disease, a factitious ulceration, or acute allergic contact dermatitis related to some element of ostomy care. However, dermatologic consultation suggested that the troublesome lesion was classic PPG and recommended administration of a tumor necrosis factor (TNF) α–blocking agent and concomitant intralesional injections of dilute triamcinolone acetonide.

The patient was treated with subcutaneous adalimumab 40 mg once weekly, and received near weekly subcutaneous injections of triamcinolone acetonide 10 mg/mL. After 2 months, the discomfort subsided, and the ulceration gradually resolved into a depressed scar. Eighteen months later, the scar was barely perceptible as a minimally erythematous depression. Adalimumab ultimately was discontinued, as the residual J-pouch was removed, and the biologic drug was associated with extensive alopecia areata–like hair loss. There has been no recurrence of PPG in the 40 months since clinical resolution.

Peristomal pyoderma gangrenosum is an uncommon subtype of pyoderma gangrenosum, which is characterized by chronic, persistent, or recurrent painful ulceration(s) close to an abdominal stoma. In total, fewer than 100 cases of PPG have been reported thus far in the readily available medical literature.³ Inflammatory bowel disease (IBD) is the most frequently diagnosed systemic condition associated with PPG, though other associated conditions include diverticular disease, abdominal malignancy, and neurologic dysfunction. Approximately 2% to 4.3% of all patients who have stoma creation surgery related to underlying IBD develop PPG. It is estimated that the yearly incidence rate of PPG in all abdominal stomas is quite low (approximately 0.6%).⁴

Peristomal pyoderma gangrenosum can occur at any age, but it tends to predominate in young to middle-aged adults, with a slight female predilection. The etiology and pathogenesis of PPG are largely unknown, though studies have shown that an abnormal immune response may be critical to its development. Risk factors for PPG are not well defined but potentially include autoimmune disorders, a high body mass index, and females or African Americans with IBD.⁴ Because PPG does not have characteristic histopathologic features, it is a diagnosis of exclusion that is based on the clinical examination and histologic findings that rule out other potential disorders.

There are 4 types of PPG based on the clinical and histopathologic characteristics: ulcerative, pustular, bullous, and vegetative. Peristomal pyoderma gangrenosum tends to be either ulcerative or vegetative, with ulcerative being by far the predominant type. The onset of PPG is quite variable, occurring a few weeks to several years after stoma formation.⁵ Ulcer size can range from less than 3 cm to 30 cm.⁴ Lesions begin as deep painful nodules or as superficial hemorrhagic pustules, either idiopathic or following ostensibly minimal trauma. Subsequently, they become necrotic and form an ulceration. The ulcers can be single or multiple lesions, typically with erythematous raised borders and purulent discharge. The ulcers are extremely painful and rapidly progressive. After the ulcers heal, they often leave a characteristic weblike atrophic scar that can break down further following any form of irritation or trauma.⁵

A prompt diagnosis of PPG is important. A diagnosis of PPG should be considered when dealing with a noninfectious ulcer surrounding a stoma in patients with IBD or other autoimmune conditions.⁶ Because PPG is a rare skin disorder, it is likely to be missed and lead to unnecessary diagnostic workup and a delay in proper therapy. In our patient, a diagnosis of PPG was overlooked for other infectious and autoimmune causes. The diagnostic evaluation of a patient with PPG is based on 3 principles: (1) ruling out other causes of a peristomal ulcer, such as an abscess, contact dermatitis, or wound infection; (2) determining whether there is an underlying intestinal bowel disease in the stoma; and (3) identifying associated systemic disorders such as vasculitis, erythema nodosum, or similar processes.⁴ The differential diagnosis depends on the type and stage of PPG and can include malignancy, vasculitis, extraintestinal IBD, infectious disease, and insect bites. A review of the history of the ulcer is helpful in ruling out other diseases, and a colonoscopy or ileoscopy can identify if patients have an underlying active IBD. Swabs for smear and both bacterial and fungal cultures should be taken from the exudate and directly from the ulcer base. Biopsy of the ulcer also helps to exclude alternative diagnoses.⁶

The primary goals of treating PPG include to reduce pain and the risk for secondary infection, increase pouch adherence, and decrease purulent exudate.⁷ Although there is not one well-defined optimal therapeutic intervention, there are a variety of effective approaches that may be considered and used. In mild cases, management methods such as dressings, topical agents, or intralesional steroids may be capable of controlling the disease. Daily wound care is important. Moisture-retentive dressings can control pain, induce collagen formation, promote angiogenesis, and prevent contamination. Cleaning the wound with sterile saline and applying an anti-infective agent also may be effective. Application of ultrapotent topical steroids and tacrolimus ointment 0.3% can be used in patients without concomitant secondary infection. In patients who are in remission, human platelet-derived growth factor may be used. Intralesional injections of dilute triamcinolone acetonide or cyclosporine solution also can be helpful. Cyclosporin A was used as a systemic monotherapy to treat a 48-year-old man and 50-year-old woman with the idiopathic form of PPG. After 3 months of treatment, PPG had completely resolved and there were no major side effects.⁸ Other potential topical therapies that control inflammation and promote wound healing include benzoyl peroxide, chlormethine (topical alkylating agent and nitrogen mustard that has anti-inflammatory properties), nicotine, and 5-aminosalicylic acid. If an ulcer becomes infected, empiric antibiotic therapy should be given immediately and adjusted based on culture and sensitivity results.⁴

Systemic therapy should be considered in patients who do not respond to topical or local interventions, have a rapid and severe course, or have an active underlying bowel disease. Oral prednisone (1 mg/kg/d) has proved to be one of the most successful drugs used to treat PPG. Treatment should be continued until complete lesion healing, and low-dose maintenance therapy should be administered in recurrent cases. Intravenous corticosteroid therapy—hydrocortisone 100 mg 4 times daily or pulse therapy with intravenous methylprednisolone 1 g/d)—can be used for up to 5 days and may be effective. Oral minocycline 100 mg twice daily may be helpful as an adjunctive therapy to corticosteroids. When corticosteroids fail, oral cyclosporine 3 to 5 mg/kg/d often is prescribed. Studies have shown that patients demonstrate clinical improvement within 3 weeks of cyclosporine initiation, and it has been shown further to be more effective than either azathioprine or methotrexate.^4,8

Infliximab, a chimeric antibody that binds both circulating and tissue-bound TNF-α, has been shown to effectively treat PPG. A clinical trial conducted by Brooklyn et al⁹ found that 46% of patients (6/13) treated with infliximab responded compared with only 6% in a placebo control group (1/17). Although infliximab may result in sepsis, the benefits far outweigh the risks, especially for patients with steroid-refractory PPG.⁴ Adalimumab is a human monoclonal IgG1 antibody to TNF-α that neutralizes its function by blocking the interaction between the molecule and its receptor. Many clinical studies have shown that adalimumab induces and maintains a clinical response in patients with active Crohn disease. The biologic proved to be effective in our patient, but it is associated with potential side effects that should be monitored including injection-site reactions, pruritus, leukopenia, urticaria, and rare instances of alopecia.¹⁰ Etanercept is another potentially effective biologic agent.⁷ Plasma exchange, immunoglobulin infusion, and interferon-alfa therapy also can be used in refractory PPG cases, though data on these treatments are very limited.⁴

Unlike routine pyoderma gangrenosum—for which surgical intervention is contraindicated—surgical intervention may be appropriate for the peristomal variant. Surgical treatment options include stoma revision and/or relocation; however, both of these procedures are accompanied by failure rates ranging from 40% to 100%.⁵ Removal of a diseased intestinal segment, especially one with active IBD, may result in healing of the skin lesion. In our patient, removal of the residual and diseased J-pouch was part of the management plan. However,it generally is recommended that any surgical intervention be accompanied by medical therapy including oral metronidazole 500 mg/d and concomitant administration of an immunosuppressant.^1,3

Because PPG tends to recur, long-term maintenance therapy should always be considered. Pain reduction, anemia correction, proper nutrition, and management of associated and underlying diseases should be performed. Meticulous care of the stoma and prevention of leaks also should be emphasized. Overall, if PPG is detected and diagnosed early as well as treated appropriately and aggressively, the patient likely will have a good prognosis.⁴

To the Editor:

Peristomal pyoderma gangrenosum (PPG) is a rare entity first described in 1984.¹ Lesions usually begin as pustules that coalesce into an erythematous skin ulceration that contains purulent material. The lesion appears on the skin that surrounds an abdominal stoma. Peristomal pyoderma gangrenosum typically is associated with Crohn disease and ulcerative colitis, cancer, blood dyscrasia, diabetes mellitus, and hepatitis.² We describe a case of PPG following an ileostomy in a patient with colon cancer and a related history of Crohn disease.

A 32-year-old woman presented to a dermatology office with a spontaneously painful, 3.2-cm ulceration that was extremely tender to palpation, located immediately adjacent to the site of an ileostomy (Figure). The patient had a history of refractory constipation that failed to respond to standard conservative measures 4 years prior. She underwent a colonoscopy, which revealed a 6.5-cm, irregularly shaped, exophytic mass in the rectosigmoid portion of the colon. Histopathologic examination of several biopsies confirmed the diagnosis of moderately well-differentiated adenocarcinoma, and additional evaluation determined the cancer to be stage IIB. She had a medical history of pancolonic Crohn disease since high school that was treated with periodic infusions of infliximab at the standard dose of 5 mg/kg. Colon cancer treatment consisted of preoperative radiotherapy, complete colectomy with ileoanal anastomosis, and creation of a J-pouch and formation of a temporary ileostomy, along with postoperative capecitabine chemotherapy.

The ileostomy eventually was reversed, and the patient did well for 3 years. When the patient developed severe abdominal pain, the J-pouch was examined and found to be remarkably involved with Crohn disease. However, during the colonoscopy, the J-pouch was inadvertently punctured, leading to the formation of a large pelvic abscess. The latter necessitated diversion of stool, and the patient had the original ileostomy recreated.

Prior to presentation to dermatology, various consultants suspected the ulceration was possibly a deep fungal infection, cutaneous Crohn disease, a factitious ulceration, or acute allergic contact dermatitis related to some element of ostomy care. However, dermatologic consultation suggested that the troublesome lesion was classic PPG and recommended administration of a tumor necrosis factor (TNF) α–blocking agent and concomitant intralesional injections of dilute triamcinolone acetonide.

The patient was treated with subcutaneous adalimumab 40 mg once weekly, and received near weekly subcutaneous injections of triamcinolone acetonide 10 mg/mL. After 2 months, the discomfort subsided, and the ulceration gradually resolved into a depressed scar. Eighteen months later, the scar was barely perceptible as a minimally erythematous depression. Adalimumab ultimately was discontinued, as the residual J-pouch was removed, and the biologic drug was associated with extensive alopecia areata–like hair loss. There has been no recurrence of PPG in the 40 months since clinical resolution.

Peristomal pyoderma gangrenosum is an uncommon subtype of pyoderma gangrenosum, which is characterized by chronic, persistent, or recurrent painful ulceration(s) close to an abdominal stoma. In total, fewer than 100 cases of PPG have been reported thus far in the readily available medical literature.³ Inflammatory bowel disease (IBD) is the most frequently diagnosed systemic condition associated with PPG, though other associated conditions include diverticular disease, abdominal malignancy, and neurologic dysfunction. Approximately 2% to 4.3% of all patients who have stoma creation surgery related to underlying IBD develop PPG. It is estimated that the yearly incidence rate of PPG in all abdominal stomas is quite low (approximately 0.6%).⁴

Peristomal pyoderma gangrenosum can occur at any age, but it tends to predominate in young to middle-aged adults, with a slight female predilection. The etiology and pathogenesis of PPG are largely unknown, though studies have shown that an abnormal immune response may be critical to its development. Risk factors for PPG are not well defined but potentially include autoimmune disorders, a high body mass index, and females or African Americans with IBD.⁴ Because PPG does not have characteristic histopathologic features, it is a diagnosis of exclusion that is based on the clinical examination and histologic findings that rule out other potential disorders.

There are 4 types of PPG based on the clinical and histopathologic characteristics: ulcerative, pustular, bullous, and vegetative. Peristomal pyoderma gangrenosum tends to be either ulcerative or vegetative, with ulcerative being by far the predominant type. The onset of PPG is quite variable, occurring a few weeks to several years after stoma formation.⁵ Ulcer size can range from less than 3 cm to 30 cm.⁴ Lesions begin as deep painful nodules or as superficial hemorrhagic pustules, either idiopathic or following ostensibly minimal trauma. Subsequently, they become necrotic and form an ulceration. The ulcers can be single or multiple lesions, typically with erythematous raised borders and purulent discharge. The ulcers are extremely painful and rapidly progressive. After the ulcers heal, they often leave a characteristic weblike atrophic scar that can break down further following any form of irritation or trauma.⁵

A prompt diagnosis of PPG is important. A diagnosis of PPG should be considered when dealing with a noninfectious ulcer surrounding a stoma in patients with IBD or other autoimmune conditions.⁶ Because PPG is a rare skin disorder, it is likely to be missed and lead to unnecessary diagnostic workup and a delay in proper therapy. In our patient, a diagnosis of PPG was overlooked for other infectious and autoimmune causes. The diagnostic evaluation of a patient with PPG is based on 3 principles: (1) ruling out other causes of a peristomal ulcer, such as an abscess, contact dermatitis, or wound infection; (2) determining whether there is an underlying intestinal bowel disease in the stoma; and (3) identifying associated systemic disorders such as vasculitis, erythema nodosum, or similar processes.⁴ The differential diagnosis depends on the type and stage of PPG and can include malignancy, vasculitis, extraintestinal IBD, infectious disease, and insect bites. A review of the history of the ulcer is helpful in ruling out other diseases, and a colonoscopy or ileoscopy can identify if patients have an underlying active IBD. Swabs for smear and both bacterial and fungal cultures should be taken from the exudate and directly from the ulcer base. Biopsy of the ulcer also helps to exclude alternative diagnoses.⁶

The primary goals of treating PPG include to reduce pain and the risk for secondary infection, increase pouch adherence, and decrease purulent exudate.⁷ Although there is not one well-defined optimal therapeutic intervention, there are a variety of effective approaches that may be considered and used. In mild cases, management methods such as dressings, topical agents, or intralesional steroids may be capable of controlling the disease. Daily wound care is important. Moisture-retentive dressings can control pain, induce collagen formation, promote angiogenesis, and prevent contamination. Cleaning the wound with sterile saline and applying an anti-infective agent also may be effective. Application of ultrapotent topical steroids and tacrolimus ointment 0.3% can be used in patients without concomitant secondary infection. In patients who are in remission, human platelet-derived growth factor may be used. Intralesional injections of dilute triamcinolone acetonide or cyclosporine solution also can be helpful. Cyclosporin A was used as a systemic monotherapy to treat a 48-year-old man and 50-year-old woman with the idiopathic form of PPG. After 3 months of treatment, PPG had completely resolved and there were no major side effects.⁸ Other potential topical therapies that control inflammation and promote wound healing include benzoyl peroxide, chlormethine (topical alkylating agent and nitrogen mustard that has anti-inflammatory properties), nicotine, and 5-aminosalicylic acid. If an ulcer becomes infected, empiric antibiotic therapy should be given immediately and adjusted based on culture and sensitivity results.⁴

Systemic therapy should be considered in patients who do not respond to topical or local interventions, have a rapid and severe course, or have an active underlying bowel disease. Oral prednisone (1 mg/kg/d) has proved to be one of the most successful drugs used to treat PPG. Treatment should be continued until complete lesion healing, and low-dose maintenance therapy should be administered in recurrent cases. Intravenous corticosteroid therapy—hydrocortisone 100 mg 4 times daily or pulse therapy with intravenous methylprednisolone 1 g/d)—can be used for up to 5 days and may be effective. Oral minocycline 100 mg twice daily may be helpful as an adjunctive therapy to corticosteroids. When corticosteroids fail, oral cyclosporine 3 to 5 mg/kg/d often is prescribed. Studies have shown that patients demonstrate clinical improvement within 3 weeks of cyclosporine initiation, and it has been shown further to be more effective than either azathioprine or methotrexate.^4,8

Infliximab, a chimeric antibody that binds both circulating and tissue-bound TNF-α, has been shown to effectively treat PPG. A clinical trial conducted by Brooklyn et al⁹ found that 46% of patients (6/13) treated with infliximab responded compared with only 6% in a placebo control group (1/17). Although infliximab may result in sepsis, the benefits far outweigh the risks, especially for patients with steroid-refractory PPG.⁴ Adalimumab is a human monoclonal IgG1 antibody to TNF-α that neutralizes its function by blocking the interaction between the molecule and its receptor. Many clinical studies have shown that adalimumab induces and maintains a clinical response in patients with active Crohn disease. The biologic proved to be effective in our patient, but it is associated with potential side effects that should be monitored including injection-site reactions, pruritus, leukopenia, urticaria, and rare instances of alopecia.¹⁰ Etanercept is another potentially effective biologic agent.⁷ Plasma exchange, immunoglobulin infusion, and interferon-alfa therapy also can be used in refractory PPG cases, though data on these treatments are very limited.⁴

Unlike routine pyoderma gangrenosum—for which surgical intervention is contraindicated—surgical intervention may be appropriate for the peristomal variant. Surgical treatment options include stoma revision and/or relocation; however, both of these procedures are accompanied by failure rates ranging from 40% to 100%.⁵ Removal of a diseased intestinal segment, especially one with active IBD, may result in healing of the skin lesion. In our patient, removal of the residual and diseased J-pouch was part of the management plan. However,it generally is recommended that any surgical intervention be accompanied by medical therapy including oral metronidazole 500 mg/d and concomitant administration of an immunosuppressant.^1,3

Because PPG tends to recur, long-term maintenance therapy should always be considered. Pain reduction, anemia correction, proper nutrition, and management of associated and underlying diseases should be performed. Meticulous care of the stoma and prevention of leaks also should be emphasized. Overall, if PPG is detected and diagnosed early as well as treated appropriately and aggressively, the patient likely will have a good prognosis.⁴

To the Editor:

Peristomal pyoderma gangrenosum (PPG) is a rare entity first described in 1984.¹ Lesions usually begin as pustules that coalesce into an erythematous skin ulceration that contains purulent material. The lesion appears on the skin that surrounds an abdominal stoma. Peristomal pyoderma gangrenosum typically is associated with Crohn disease and ulcerative colitis, cancer, blood dyscrasia, diabetes mellitus, and hepatitis.² We describe a case of PPG following an ileostomy in a patient with colon cancer and a related history of Crohn disease.

A 32-year-old woman presented to a dermatology office with a spontaneously painful, 3.2-cm ulceration that was extremely tender to palpation, located immediately adjacent to the site of an ileostomy (Figure). The patient had a history of refractory constipation that failed to respond to standard conservative measures 4 years prior. She underwent a colonoscopy, which revealed a 6.5-cm, irregularly shaped, exophytic mass in the rectosigmoid portion of the colon. Histopathologic examination of several biopsies confirmed the diagnosis of moderately well-differentiated adenocarcinoma, and additional evaluation determined the cancer to be stage IIB. She had a medical history of pancolonic Crohn disease since high school that was treated with periodic infusions of infliximab at the standard dose of 5 mg/kg. Colon cancer treatment consisted of preoperative radiotherapy, complete colectomy with ileoanal anastomosis, and creation of a J-pouch and formation of a temporary ileostomy, along with postoperative capecitabine chemotherapy.

The ileostomy eventually was reversed, and the patient did well for 3 years. When the patient developed severe abdominal pain, the J-pouch was examined and found to be remarkably involved with Crohn disease. However, during the colonoscopy, the J-pouch was inadvertently punctured, leading to the formation of a large pelvic abscess. The latter necessitated diversion of stool, and the patient had the original ileostomy recreated.

Prior to presentation to dermatology, various consultants suspected the ulceration was possibly a deep fungal infection, cutaneous Crohn disease, a factitious ulceration, or acute allergic contact dermatitis related to some element of ostomy care. However, dermatologic consultation suggested that the troublesome lesion was classic PPG and recommended administration of a tumor necrosis factor (TNF) α–blocking agent and concomitant intralesional injections of dilute triamcinolone acetonide.

The patient was treated with subcutaneous adalimumab 40 mg once weekly, and received near weekly subcutaneous injections of triamcinolone acetonide 10 mg/mL. After 2 months, the discomfort subsided, and the ulceration gradually resolved into a depressed scar. Eighteen months later, the scar was barely perceptible as a minimally erythematous depression. Adalimumab ultimately was discontinued, as the residual J-pouch was removed, and the biologic drug was associated with extensive alopecia areata–like hair loss. There has been no recurrence of PPG in the 40 months since clinical resolution.

Peristomal pyoderma gangrenosum is an uncommon subtype of pyoderma gangrenosum, which is characterized by chronic, persistent, or recurrent painful ulceration(s) close to an abdominal stoma. In total, fewer than 100 cases of PPG have been reported thus far in the readily available medical literature.³ Inflammatory bowel disease (IBD) is the most frequently diagnosed systemic condition associated with PPG, though other associated conditions include diverticular disease, abdominal malignancy, and neurologic dysfunction. Approximately 2% to 4.3% of all patients who have stoma creation surgery related to underlying IBD develop PPG. It is estimated that the yearly incidence rate of PPG in all abdominal stomas is quite low (approximately 0.6%).⁴

Peristomal pyoderma gangrenosum can occur at any age, but it tends to predominate in young to middle-aged adults, with a slight female predilection. The etiology and pathogenesis of PPG are largely unknown, though studies have shown that an abnormal immune response may be critical to its development. Risk factors for PPG are not well defined but potentially include autoimmune disorders, a high body mass index, and females or African Americans with IBD.⁴ Because PPG does not have characteristic histopathologic features, it is a diagnosis of exclusion that is based on the clinical examination and histologic findings that rule out other potential disorders.

There are 4 types of PPG based on the clinical and histopathologic characteristics: ulcerative, pustular, bullous, and vegetative. Peristomal pyoderma gangrenosum tends to be either ulcerative or vegetative, with ulcerative being by far the predominant type. The onset of PPG is quite variable, occurring a few weeks to several years after stoma formation.⁵ Ulcer size can range from less than 3 cm to 30 cm.⁴ Lesions begin as deep painful nodules or as superficial hemorrhagic pustules, either idiopathic or following ostensibly minimal trauma. Subsequently, they become necrotic and form an ulceration. The ulcers can be single or multiple lesions, typically with erythematous raised borders and purulent discharge. The ulcers are extremely painful and rapidly progressive. After the ulcers heal, they often leave a characteristic weblike atrophic scar that can break down further following any form of irritation or trauma.⁵

A prompt diagnosis of PPG is important. A diagnosis of PPG should be considered when dealing with a noninfectious ulcer surrounding a stoma in patients with IBD or other autoimmune conditions.⁶ Because PPG is a rare skin disorder, it is likely to be missed and lead to unnecessary diagnostic workup and a delay in proper therapy. In our patient, a diagnosis of PPG was overlooked for other infectious and autoimmune causes. The diagnostic evaluation of a patient with PPG is based on 3 principles: (1) ruling out other causes of a peristomal ulcer, such as an abscess, contact dermatitis, or wound infection; (2) determining whether there is an underlying intestinal bowel disease in the stoma; and (3) identifying associated systemic disorders such as vasculitis, erythema nodosum, or similar processes.⁴ The differential diagnosis depends on the type and stage of PPG and can include malignancy, vasculitis, extraintestinal IBD, infectious disease, and insect bites. A review of the history of the ulcer is helpful in ruling out other diseases, and a colonoscopy or ileoscopy can identify if patients have an underlying active IBD. Swabs for smear and both bacterial and fungal cultures should be taken from the exudate and directly from the ulcer base. Biopsy of the ulcer also helps to exclude alternative diagnoses.⁶

The primary goals of treating PPG include to reduce pain and the risk for secondary infection, increase pouch adherence, and decrease purulent exudate.⁷ Although there is not one well-defined optimal therapeutic intervention, there are a variety of effective approaches that may be considered and used. In mild cases, management methods such as dressings, topical agents, or intralesional steroids may be capable of controlling the disease. Daily wound care is important. Moisture-retentive dressings can control pain, induce collagen formation, promote angiogenesis, and prevent contamination. Cleaning the wound with sterile saline and applying an anti-infective agent also may be effective. Application of ultrapotent topical steroids and tacrolimus ointment 0.3% can be used in patients without concomitant secondary infection. In patients who are in remission, human platelet-derived growth factor may be used. Intralesional injections of dilute triamcinolone acetonide or cyclosporine solution also can be helpful. Cyclosporin A was used as a systemic monotherapy to treat a 48-year-old man and 50-year-old woman with the idiopathic form of PPG. After 3 months of treatment, PPG had completely resolved and there were no major side effects.⁸ Other potential topical therapies that control inflammation and promote wound healing include benzoyl peroxide, chlormethine (topical alkylating agent and nitrogen mustard that has anti-inflammatory properties), nicotine, and 5-aminosalicylic acid. If an ulcer becomes infected, empiric antibiotic therapy should be given immediately and adjusted based on culture and sensitivity results.⁴

Systemic therapy should be considered in patients who do not respond to topical or local interventions, have a rapid and severe course, or have an active underlying bowel disease. Oral prednisone (1 mg/kg/d) has proved to be one of the most successful drugs used to treat PPG. Treatment should be continued until complete lesion healing, and low-dose maintenance therapy should be administered in recurrent cases. Intravenous corticosteroid therapy—hydrocortisone 100 mg 4 times daily or pulse therapy with intravenous methylprednisolone 1 g/d)—can be used for up to 5 days and may be effective. Oral minocycline 100 mg twice daily may be helpful as an adjunctive therapy to corticosteroids. When corticosteroids fail, oral cyclosporine 3 to 5 mg/kg/d often is prescribed. Studies have shown that patients demonstrate clinical improvement within 3 weeks of cyclosporine initiation, and it has been shown further to be more effective than either azathioprine or methotrexate.^4,8

Infliximab, a chimeric antibody that binds both circulating and tissue-bound TNF-α, has been shown to effectively treat PPG. A clinical trial conducted by Brooklyn et al⁹ found that 46% of patients (6/13) treated with infliximab responded compared with only 6% in a placebo control group (1/17). Although infliximab may result in sepsis, the benefits far outweigh the risks, especially for patients with steroid-refractory PPG.⁴ Adalimumab is a human monoclonal IgG1 antibody to TNF-α that neutralizes its function by blocking the interaction between the molecule and its receptor. Many clinical studies have shown that adalimumab induces and maintains a clinical response in patients with active Crohn disease. The biologic proved to be effective in our patient, but it is associated with potential side effects that should be monitored including injection-site reactions, pruritus, leukopenia, urticaria, and rare instances of alopecia.¹⁰ Etanercept is another potentially effective biologic agent.⁷ Plasma exchange, immunoglobulin infusion, and interferon-alfa therapy also can be used in refractory PPG cases, though data on these treatments are very limited.⁴

Unlike routine pyoderma gangrenosum—for which surgical intervention is contraindicated—surgical intervention may be appropriate for the peristomal variant. Surgical treatment options include stoma revision and/or relocation; however, both of these procedures are accompanied by failure rates ranging from 40% to 100%.⁵ Removal of a diseased intestinal segment, especially one with active IBD, may result in healing of the skin lesion. In our patient, removal of the residual and diseased J-pouch was part of the management plan. However,it generally is recommended that any surgical intervention be accompanied by medical therapy including oral metronidazole 500 mg/d and concomitant administration of an immunosuppressant.^1,3

Because PPG tends to recur, long-term maintenance therapy should always be considered. Pain reduction, anemia correction, proper nutrition, and management of associated and underlying diseases should be performed. Meticulous care of the stoma and prevention of leaks also should be emphasized. Overall, if PPG is detected and diagnosed early as well as treated appropriately and aggressively, the patient likely will have a good prognosis.⁴

Shave biopsy was consistent with a solitary periungual angiofibroma, often termed a Koenen tumor. These can manifest as a soft pink papule (as with this patient), sometimes with a distal keratinaceous tip. At times, the nail bed and nail plate may be deformed because of the angiofibroma.

Periungual angiofibromas can occur sporadically in children and adults, it was a solitary finding in this case. Importantly, periungual angiofibromas may also occur as a visible sign of a multisystem genetic disorder known as tuberous sclerosis complex (TSC). TSC causes benign tumors to develop throughout the body (eg, skin, brain, heart, lungs). The condition can be mild or lead to serious disabilities, including seizures and developmental delays.

In isolation, periungual angiofibromas are benign but occasionally hurt or bleed from light trauma. In such cases, or for cosmetic reasons, patients may seek treatments. Complete excision of the lesion may include the affected portion of the nail bed or matrix. This is more easily repaired when the lesion is on the lateral nail fold, facilitating an en bloc fusiform excision and matrixectomy.¹ Surgical excision of a lesion in the mid-proximal nail fold is much more likely to result in long-term nail deformity. Electrosurgery and various laser modalities have been successful as less invasive removal options.² While expensive, topical sirolimus 1% has been used successfully in sporadic angiofibromas and those associated with TSC.

The patient in this case underwent lateral nail fold excision with complete removal of the tumor and repair with a side-to-side closure.

‌

Text courtesy of Jonathan Karnes, MD, medical director, MDFMR Dermatology Services, Augusta, ME. Photos courtesy of Jonathan Karnes, MD (copyright retained).

Shave biopsy was consistent with a solitary periungual angiofibroma, often termed a Koenen tumor. These can manifest as a soft pink papule (as with this patient), sometimes with a distal keratinaceous tip. At times, the nail bed and nail plate may be deformed because of the angiofibroma.

Periungual angiofibromas can occur sporadically in children and adults, it was a solitary finding in this case. Importantly, periungual angiofibromas may also occur as a visible sign of a multisystem genetic disorder known as tuberous sclerosis complex (TSC). TSC causes benign tumors to develop throughout the body (eg, skin, brain, heart, lungs). The condition can be mild or lead to serious disabilities, including seizures and developmental delays.

In isolation, periungual angiofibromas are benign but occasionally hurt or bleed from light trauma. In such cases, or for cosmetic reasons, patients may seek treatments. Complete excision of the lesion may include the affected portion of the nail bed or matrix. This is more easily repaired when the lesion is on the lateral nail fold, facilitating an en bloc fusiform excision and matrixectomy.¹ Surgical excision of a lesion in the mid-proximal nail fold is much more likely to result in long-term nail deformity. Electrosurgery and various laser modalities have been successful as less invasive removal options.² While expensive, topical sirolimus 1% has been used successfully in sporadic angiofibromas and those associated with TSC.

The patient in this case underwent lateral nail fold excision with complete removal of the tumor and repair with a side-to-side closure.

‌

Text courtesy of Jonathan Karnes, MD, medical director, MDFMR Dermatology Services, Augusta, ME. Photos courtesy of Jonathan Karnes, MD (copyright retained).

Shave biopsy was consistent with a solitary periungual angiofibroma, often termed a Koenen tumor. These can manifest as a soft pink papule (as with this patient), sometimes with a distal keratinaceous tip. At times, the nail bed and nail plate may be deformed because of the angiofibroma.

Periungual angiofibromas can occur sporadically in children and adults, it was a solitary finding in this case. Importantly, periungual angiofibromas may also occur as a visible sign of a multisystem genetic disorder known as tuberous sclerosis complex (TSC). TSC causes benign tumors to develop throughout the body (eg, skin, brain, heart, lungs). The condition can be mild or lead to serious disabilities, including seizures and developmental delays.

In isolation, periungual angiofibromas are benign but occasionally hurt or bleed from light trauma. In such cases, or for cosmetic reasons, patients may seek treatments. Complete excision of the lesion may include the affected portion of the nail bed or matrix. This is more easily repaired when the lesion is on the lateral nail fold, facilitating an en bloc fusiform excision and matrixectomy.¹ Surgical excision of a lesion in the mid-proximal nail fold is much more likely to result in long-term nail deformity. Electrosurgery and various laser modalities have been successful as less invasive removal options.² While expensive, topical sirolimus 1% has been used successfully in sporadic angiofibromas and those associated with TSC.

The patient in this case underwent lateral nail fold excision with complete removal of the tumor and repair with a side-to-side closure.

‌

Text courtesy of Jonathan Karnes, MD, medical director, MDFMR Dermatology Services, Augusta, ME. Photos courtesy of Jonathan Karnes, MD (copyright retained).

Key clinical point: Both probiotic and drug interventions decreased the persistence of irritable bowel syndrome (IBS) symptoms and abdominal pain scores compared with placebo in patients with IBS.

Major finding: Compared with placebo, both probiotic and drug interventions improved the persistence of IBS symptoms (relative risk [RR] 0.68; 95% CI 0.51-0.92, and RR 0.87; 95% CI 0.81-0.92, respectively) and abdominal pain scores (standardized mean difference [SMD] −0.35; 95% CI −0.56 to −0.14, and SMD −0.10; 95% CI −0.20 to 0.00, respectively).

Study details Findings are from a systematic review and meta-analysis of 32 randomized controlled trials including adults with IBS.

Disclosures: This study did not receive financial support. The authors declared being scientific advisory board members or serving as consultants for various sources.

Source: van der Geest AM et al. Comparing probiotic and drug interventions in irritable bowel syndrome: A meta-analysis of randomised controlled trials. Benef Microbes. 2022 (Jul 18). Doi: 10.3920/BM2021.0123

Key clinical point: Both probiotic and drug interventions decreased the persistence of irritable bowel syndrome (IBS) symptoms and abdominal pain scores compared with placebo in patients with IBS.

Major finding: Compared with placebo, both probiotic and drug interventions improved the persistence of IBS symptoms (relative risk [RR] 0.68; 95% CI 0.51-0.92, and RR 0.87; 95% CI 0.81-0.92, respectively) and abdominal pain scores (standardized mean difference [SMD] −0.35; 95% CI −0.56 to −0.14, and SMD −0.10; 95% CI −0.20 to 0.00, respectively).

Study details Findings are from a systematic review and meta-analysis of 32 randomized controlled trials including adults with IBS.

Disclosures: This study did not receive financial support. The authors declared being scientific advisory board members or serving as consultants for various sources.

Source: van der Geest AM et al. Comparing probiotic and drug interventions in irritable bowel syndrome: A meta-analysis of randomised controlled trials. Benef Microbes. 2022 (Jul 18). Doi: 10.3920/BM2021.0123

Key clinical point: Both probiotic and drug interventions decreased the persistence of irritable bowel syndrome (IBS) symptoms and abdominal pain scores compared with placebo in patients with IBS.

Major finding: Compared with placebo, both probiotic and drug interventions improved the persistence of IBS symptoms (relative risk [RR] 0.68; 95% CI 0.51-0.92, and RR 0.87; 95% CI 0.81-0.92, respectively) and abdominal pain scores (standardized mean difference [SMD] −0.35; 95% CI −0.56 to −0.14, and SMD −0.10; 95% CI −0.20 to 0.00, respectively).

Study details Findings are from a systematic review and meta-analysis of 32 randomized controlled trials including adults with IBS.

Disclosures: This study did not receive financial support. The authors declared being scientific advisory board members or serving as consultants for various sources.

Source: van der Geest AM et al. Comparing probiotic and drug interventions in irritable bowel syndrome: A meta-analysis of randomised controlled trials. Benef Microbes. 2022 (Jul 18). Doi: 10.3920/BM2021.0123

Key clinical point: Fecal microbiota transplantation (FMT) reduced disease severity, improved microbiome α-diversity, and demonstrated a favorable safety profile in patients with refractory irritable bowel syndrome (IBS).

Major finding: The IBS severity index improved significantly at 12 weeks after FMT (P  =  .001), with 58.8% of patients being responders (≥50-point decrease in IBS severity index). Responders showed a significant increase in the median α-diversity index (P  =  .017), increased abundance of Neisseria and Akkermansia bacteria, and decreased abundance of Desulfovibrio and Delftia bacteria. No severe adverse events were reported.

Study details Findings are from a prospective study including 17 patients with refractory IBS who received FMT under colonoscopy.

Disclosures: This study was partly supported by the Japan Society for the Promotion of Science. The authors declared no conflicts of interest.

Source: Hamazaki M et al. Fecal microbiota transplantation in the treatment of irritable bowel syndrome: A single-center prospective study in Japan. BMC Gastroenterol. 2022;22:342 (Jul 14). Doi: 10.1186/s12876-022-02408-5

Key clinical point: Fecal microbiota transplantation (FMT) reduced disease severity, improved microbiome α-diversity, and demonstrated a favorable safety profile in patients with refractory irritable bowel syndrome (IBS).

Major finding: The IBS severity index improved significantly at 12 weeks after FMT (P  =  .001), with 58.8% of patients being responders (≥50-point decrease in IBS severity index). Responders showed a significant increase in the median α-diversity index (P  =  .017), increased abundance of Neisseria and Akkermansia bacteria, and decreased abundance of Desulfovibrio and Delftia bacteria. No severe adverse events were reported.

Study details Findings are from a prospective study including 17 patients with refractory IBS who received FMT under colonoscopy.

Disclosures: This study was partly supported by the Japan Society for the Promotion of Science. The authors declared no conflicts of interest.

Source: Hamazaki M et al. Fecal microbiota transplantation in the treatment of irritable bowel syndrome: A single-center prospective study in Japan. BMC Gastroenterol. 2022;22:342 (Jul 14). Doi: 10.1186/s12876-022-02408-5

Key clinical point: Fecal microbiota transplantation (FMT) reduced disease severity, improved microbiome α-diversity, and demonstrated a favorable safety profile in patients with refractory irritable bowel syndrome (IBS).

Major finding: The IBS severity index improved significantly at 12 weeks after FMT (P  =  .001), with 58.8% of patients being responders (≥50-point decrease in IBS severity index). Responders showed a significant increase in the median α-diversity index (P  =  .017), increased abundance of Neisseria and Akkermansia bacteria, and decreased abundance of Desulfovibrio and Delftia bacteria. No severe adverse events were reported.

Study details Findings are from a prospective study including 17 patients with refractory IBS who received FMT under colonoscopy.

Disclosures: This study was partly supported by the Japan Society for the Promotion of Science. The authors declared no conflicts of interest.

Source: Hamazaki M et al. Fecal microbiota transplantation in the treatment of irritable bowel syndrome: A single-center prospective study in Japan. BMC Gastroenterol. 2022;22:342 (Jul 14). Doi: 10.1186/s12876-022-02408-5

Key clinical point: Patients with irritable bowel syndrome (IBS) report a substantial impact of IBS on their abilities to work and perform daily activities.

Major finding: Overall, 10.5% of patients reported being unemployed, partly because of their condition, with the median level of absenteeism, presenteeism, and overall work impairment among employed patients being 0.0% (interquartile range [IQR] 0.0%-2.9%), 35.0% (IQR, 20.0%-60.0%), and 30.0% (IQR, 10.0%-60.0%), respectively. Moreover, 91.0% and 56.3% of patients reported that IBS symptoms interfered with their daily and social leisure activities, respectively.

Study details: This was a questionnaire-based study including 752 patients with Rome IV-defined IBS.

Disclosures: This study was supported by Tillotts Pharma UK Ltd. The authors declared no conflicts of interest.

Source: Goodoory VC et al. Impact of Rome IV irritable bowel syndrome on work and activities of daily living .Aliment Pharmacol Ther. 2022 (Jul 6). Doi: 10.1111/apt.17132

Key clinical point: Patients with irritable bowel syndrome (IBS) report a substantial impact of IBS on their abilities to work and perform daily activities.

Major finding: Overall, 10.5% of patients reported being unemployed, partly because of their condition, with the median level of absenteeism, presenteeism, and overall work impairment among employed patients being 0.0% (interquartile range [IQR] 0.0%-2.9%), 35.0% (IQR, 20.0%-60.0%), and 30.0% (IQR, 10.0%-60.0%), respectively. Moreover, 91.0% and 56.3% of patients reported that IBS symptoms interfered with their daily and social leisure activities, respectively.

Study details: This was a questionnaire-based study including 752 patients with Rome IV-defined IBS.

Disclosures: This study was supported by Tillotts Pharma UK Ltd. The authors declared no conflicts of interest.

Source: Goodoory VC et al. Impact of Rome IV irritable bowel syndrome on work and activities of daily living .Aliment Pharmacol Ther. 2022 (Jul 6). Doi: 10.1111/apt.17132

Key clinical point: Patients with irritable bowel syndrome (IBS) report a substantial impact of IBS on their abilities to work and perform daily activities.

Major finding: Overall, 10.5% of patients reported being unemployed, partly because of their condition, with the median level of absenteeism, presenteeism, and overall work impairment among employed patients being 0.0% (interquartile range [IQR] 0.0%-2.9%), 35.0% (IQR, 20.0%-60.0%), and 30.0% (IQR, 10.0%-60.0%), respectively. Moreover, 91.0% and 56.3% of patients reported that IBS symptoms interfered with their daily and social leisure activities, respectively.

Study details: This was a questionnaire-based study including 752 patients with Rome IV-defined IBS.

Disclosures: This study was supported by Tillotts Pharma UK Ltd. The authors declared no conflicts of interest.

Source: Goodoory VC et al. Impact of Rome IV irritable bowel syndrome on work and activities of daily living .Aliment Pharmacol Ther. 2022 (Jul 6). Doi: 10.1111/apt.17132

Key clinical point: In patients with constipation-predominant irritable bowel syndrome (IBS-C), short-term treatment with probiotics vs placebo led to a significant improvement in stool consistency and increased the number of fecal bacteria without increasing adverse events.

Major finding: Probiotics vs placebo significantly improved stool consistency (mean difference [MD] 0.71; P < .05) in 8 weeks and increased the number of fecal Bifidobacterium (MD 1.76; P < .05) and Lactobacillus (MD 1.69; P < .05) in 4 weeks, although the effects were not significant with longer treatment duration. Adverse effects were not significantly different between the probiotic and placebo groups.

Study details Findings are from a systematic review and meta-analysis of 10 randomized controlled trials including 757 patients with IBS-C.

Disclosures: This study was supported by the National Natural Science Foundation of China, the Gansu Special Project of Soft Science, and others. The authors declared no conflicts of interest.

Source: Shang X et al. Effectiveness and safety of probiotics for patients with constipation-predominant irritable bowel syndrome: A systematic review and meta-analysis of 10 randomized controlled trials. Nutrients. 2022;14(12):2482 (Jun 15). Doi: 10.3390/nu14122482

Key clinical point: In patients with constipation-predominant irritable bowel syndrome (IBS-C), short-term treatment with probiotics vs placebo led to a significant improvement in stool consistency and increased the number of fecal bacteria without increasing adverse events.

Major finding: Probiotics vs placebo significantly improved stool consistency (mean difference [MD] 0.71; P < .05) in 8 weeks and increased the number of fecal Bifidobacterium (MD 1.76; P < .05) and Lactobacillus (MD 1.69; P < .05) in 4 weeks, although the effects were not significant with longer treatment duration. Adverse effects were not significantly different between the probiotic and placebo groups.

Study details Findings are from a systematic review and meta-analysis of 10 randomized controlled trials including 757 patients with IBS-C.

Disclosures: This study was supported by the National Natural Science Foundation of China, the Gansu Special Project of Soft Science, and others. The authors declared no conflicts of interest.

Source: Shang X et al. Effectiveness and safety of probiotics for patients with constipation-predominant irritable bowel syndrome: A systematic review and meta-analysis of 10 randomized controlled trials. Nutrients. 2022;14(12):2482 (Jun 15). Doi: 10.3390/nu14122482

Key clinical point: In patients with constipation-predominant irritable bowel syndrome (IBS-C), short-term treatment with probiotics vs placebo led to a significant improvement in stool consistency and increased the number of fecal bacteria without increasing adverse events.

Major finding: Probiotics vs placebo significantly improved stool consistency (mean difference [MD] 0.71; P < .05) in 8 weeks and increased the number of fecal Bifidobacterium (MD 1.76; P < .05) and Lactobacillus (MD 1.69; P < .05) in 4 weeks, although the effects were not significant with longer treatment duration. Adverse effects were not significantly different between the probiotic and placebo groups.

Study details Findings are from a systematic review and meta-analysis of 10 randomized controlled trials including 757 patients with IBS-C.

Disclosures: This study was supported by the National Natural Science Foundation of China, the Gansu Special Project of Soft Science, and others. The authors declared no conflicts of interest.

Source: Shang X et al. Effectiveness and safety of probiotics for patients with constipation-predominant irritable bowel syndrome: A systematic review and meta-analysis of 10 randomized controlled trials. Nutrients. 2022;14(12):2482 (Jun 15). Doi: 10.3390/nu14122482

Key clinical point: Food supplements containing standardized menthol, limonene, and gingerol content significantly improved the efficacy of standard treatment in patients with irritable bowel syndrome (IBS) or IBS/functional dyspepsia (FD) without causing any obvious side effects.

Major finding: At visit 1 (before treatment), the median 7×7 questionnaire score of all patients indicated moderate illness. However, at visit 3, the score range indicated borderline illness in patients who received the food supplement and mild illness in those who received placebo (mean difference, −2.68; P  =  .009). No side effects were reported.

Study details Findings are from a randomized controlled trial including 56 patients with IBS or IBS/FD who were randomly assigned to receive food supplements or placebo in addition to the standard treatment regimen for 30 days.

Disclosures: This study did not receive any funding. The authors declared no conflicts of interest.

Source: Ivashkin VT et al. Efficacy and safety of a food supplement with standardized menthol, limonene, and gingerol content in patients with irritable bowel syndrome: A double-blind, randomized, placebo-controlled trial. PloS One. 2022;17(6):e0263880 (Jun 15). Doi: 10.1371/journal.pone.0263880

Key clinical point: Food supplements containing standardized menthol, limonene, and gingerol content significantly improved the efficacy of standard treatment in patients with irritable bowel syndrome (IBS) or IBS/functional dyspepsia (FD) without causing any obvious side effects.

Major finding: At visit 1 (before treatment), the median 7×7 questionnaire score of all patients indicated moderate illness. However, at visit 3, the score range indicated borderline illness in patients who received the food supplement and mild illness in those who received placebo (mean difference, −2.68; P  =  .009). No side effects were reported.

Study details Findings are from a randomized controlled trial including 56 patients with IBS or IBS/FD who were randomly assigned to receive food supplements or placebo in addition to the standard treatment regimen for 30 days.

Disclosures: This study did not receive any funding. The authors declared no conflicts of interest.

Source: Ivashkin VT et al. Efficacy and safety of a food supplement with standardized menthol, limonene, and gingerol content in patients with irritable bowel syndrome: A double-blind, randomized, placebo-controlled trial. PloS One. 2022;17(6):e0263880 (Jun 15). Doi: 10.1371/journal.pone.0263880

Key clinical point: Food supplements containing standardized menthol, limonene, and gingerol content significantly improved the efficacy of standard treatment in patients with irritable bowel syndrome (IBS) or IBS/functional dyspepsia (FD) without causing any obvious side effects.

Major finding: At visit 1 (before treatment), the median 7×7 questionnaire score of all patients indicated moderate illness. However, at visit 3, the score range indicated borderline illness in patients who received the food supplement and mild illness in those who received placebo (mean difference, −2.68; P  =  .009). No side effects were reported.

Study details Findings are from a randomized controlled trial including 56 patients with IBS or IBS/FD who were randomly assigned to receive food supplements or placebo in addition to the standard treatment regimen for 30 days.

Disclosures: This study did not receive any funding. The authors declared no conflicts of interest.

Source: Ivashkin VT et al. Efficacy and safety of a food supplement with standardized menthol, limonene, and gingerol content in patients with irritable bowel syndrome: A double-blind, randomized, placebo-controlled trial. PloS One. 2022;17(6):e0263880 (Jun 15). Doi: 10.1371/journal.pone.0263880

Key clinical point: Patients with diarrhea-predominant irritable bowel syndrome (IBS-D) vs healthy controls had lower serum zinc levels and poor scores for the quality of life (QoL) and physical and psychological health, and higher scores for depression, anxiety, and stress.

Major finding: Patients with IBS-D vs healthy controls reported significantly lower serum zinc levels (P  =  .001); mean scores for overall QoL and general health (53.48 vs 72.74; P ≤ .001), physical health (59.59 vs 71.30; P ≤ .001), and psychological health (55.80 vs 65.22; P ≤ .001); and higher mean scores for depression (P  =  .014), anxiety (P  =  .005), and stress (P  =  .001). Higher dietary zinc intake improved body image in patients with IBS-D (r 0.266; P  =  .044) without significantly influencing other parameters.

Study details: This was a case-control study including patients newly diagnosed with IBS-D (n = 61) and matched healthy controls (n = 61).

Disclosures: This study was supported by the Vice-Chancellor for Research of Isfahan University of Medical Sciences. The authors declared no conflicts of interest.

Source: Rezazadegan M et al. Sci Rep. 2022 Jun 29. doi: 10.1038/s41598-022-15080-2.

Key clinical point: Patients with diarrhea-predominant irritable bowel syndrome (IBS-D) vs healthy controls had lower serum zinc levels and poor scores for the quality of life (QoL) and physical and psychological health, and higher scores for depression, anxiety, and stress.

Major finding: Patients with IBS-D vs healthy controls reported significantly lower serum zinc levels (P  =  .001); mean scores for overall QoL and general health (53.48 vs 72.74; P ≤ .001), physical health (59.59 vs 71.30; P ≤ .001), and psychological health (55.80 vs 65.22; P ≤ .001); and higher mean scores for depression (P  =  .014), anxiety (P  =  .005), and stress (P  =  .001). Higher dietary zinc intake improved body image in patients with IBS-D (r 0.266; P  =  .044) without significantly influencing other parameters.

Study details: This was a case-control study including patients newly diagnosed with IBS-D (n = 61) and matched healthy controls (n = 61).

Disclosures: This study was supported by the Vice-Chancellor for Research of Isfahan University of Medical Sciences. The authors declared no conflicts of interest.

Source: Rezazadegan M et al. Sci Rep. 2022 Jun 29. doi: 10.1038/s41598-022-15080-2.

Key clinical point: Patients with diarrhea-predominant irritable bowel syndrome (IBS-D) vs healthy controls had lower serum zinc levels and poor scores for the quality of life (QoL) and physical and psychological health, and higher scores for depression, anxiety, and stress.

Major finding: Patients with IBS-D vs healthy controls reported significantly lower serum zinc levels (P  =  .001); mean scores for overall QoL and general health (53.48 vs 72.74; P ≤ .001), physical health (59.59 vs 71.30; P ≤ .001), and psychological health (55.80 vs 65.22; P ≤ .001); and higher mean scores for depression (P  =  .014), anxiety (P  =  .005), and stress (P  =  .001). Higher dietary zinc intake improved body image in patients with IBS-D (r 0.266; P  =  .044) without significantly influencing other parameters.

Study details: This was a case-control study including patients newly diagnosed with IBS-D (n = 61) and matched healthy controls (n = 61).

Disclosures: This study was supported by the Vice-Chancellor for Research of Isfahan University of Medical Sciences. The authors declared no conflicts of interest.

Source: Rezazadegan M et al. Sci Rep. 2022 Jun 29. doi: 10.1038/s41598-022-15080-2.