BRIEF REPORT Pediatric Dermatology Vol. 31 No. 2 e61–e62, 2014
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Bullous Sweet’s Syndrome After Granulocyte Colony-Stimulating Factor Therapy in a Child with Congenital Neutropenia Abstract: We present the case of a 20-month-old boy with congenital neutropenia for which he was being treated with granulocyte colony-stimulating factor (G-CSF) who developed bullous Sweet’s syndrome. Because of the challenging and extensive differential diagnosis of an acute bullous eruption in an immunocompromised child, we highlight the importance of a prompt and precise diagnosis before initiation of any systemic therapy in children with Sweet’s syndrome.
A 20-month-old Caucasian boy with a history of a genetic immunodeficiency was being treated with subcutaneous granulocyte colony-stimulating factor (G-CSF). His immunodeficiency was characterized by neutropenia, CD4+ lymphopenia, and hypogammaglobulinemia. He developed widespread symmetric, tender, flesh-colored to white, edematous coalescent plaques and tense bullae up to 1 cm in diameter on a noninflammatory background (Fig. 1A). The lesions were first noted on the back of his neck and then eventually spread to his extremities, sparing the trunk and ears. New lesions appeared at sites of intravenous injection. A review of systems was negative for any signs of infections. He continued to receive Pneumocystis jiroveci pneumonia prophylaxis with sulfamethoxazole and trimethoprim and fungal prophylaxis with itraconazole. Multiple blood and tissue cultures were negative for herpes simplex and varicella zoster viruses, bacteria, and fungi. Several skin biopsies revealed a spongiotic epidermis with a central collapsed vesicle containing neutrophils (Fig. 2). A confluent population of neutrophils surrounded the vessels and adnexa and extended throughout the dermis. No true leukocytoclastic vasculitis was appreciated. No viral inclusions were seen. No organisms were seen on periodic acid– Schiff or Grocott stains. Immunofluorescence was
DOI: 10.1111/pde.12282
© 2014 Wiley Periodicals, Inc.
Figure 1. (A) Generalized confluent, tense, painful bullae with mild hyperemic rims on the extensor surfaces of the lower extremities. (B) Rapid improvement 3 days after initiation of therapy with 0.5 mg/kg of oral prednisone.
negative for staining of immunoglobulin (Ig)A, IgG, and IgM. The patient was diagnosed with bullous Sweet’s syndrome and started on a 4-week course of oral prednisone at 2 mg/kg/day. G-CSF was suspected as a causative medication and was discontinued. He responded to this therapy with rapid clearing of the lesions as soon as day 3 after initiation of systemic steroids (Fig. 1B). Absolute neutropenia resolved while on steroids, whereas absolute lymphopenia remained unchanged. At the 1-month follow-up, the patient had only faintly erythematous round macules on his neck, back, chest, bilateral arms, hands, and legs. DISCUSSION Acute febrile neutrophilic dermatosis (Sweet’s syndrome) in children is most commonly idiopathic. Most often the precipitating event is a viral infection, with or without immunodeficiency. Many immunodeficient conditions associated with Sweet’s syndrome have been reported. Frequently the immunodeficient condition itself does not precipitate the Sweet’s syndrome. Rather, the treatment for this condition leads to an excess of neutrophils and induces differentiation and maturation of myeloid precursors, as observed in cases of retinoids (1) and G-CSF (2). It has been postulated that G-CSF-induced Sweet’s syndrome occurs when the number of neutrophils
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e62 Pediatric Dermatology Vol. 31 No. 2 March/April 2014
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Systemic corticosteroids are the criterion standard of therapy for Sweet’s syndrome (4). Oral prednisone 0.5 to 1.5 mg/kg/day tapered over 6 weeks results in the rapid relief of systemic symptoms and skin lesions within 7 days (5), although the relapse rate (30%) is high, requiring the patient to have a prolonged course or an additional immunosuppressive agent. We present an uncommon bullous variant of Sweet’s syndrome in a child with congenital neutropenia who was receiving treatment with G-CSF. Prompt diagnosis based on multiple negative bacterial and viral cultures, the presence of pathergy phenomenon, and supportive histologic examination was crucial before the initiation of systemic corticosteroids, which resulted in a rapid improvement. REFERENCES
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Figure 2. (A) Prominent papillary dermal edema and the formation of subepidermal bulla. (B) A dense neutrophilic infiltrate without evidence of primary leukocytoclastic vasculitis.
reaches some threshold at which cytokine dysregulation draws mature neutrophils into the skin (3).
1. Piette WW, Trapp JF, O’Donnell MJ et al. Acute neutrophilic dermatosis with myeloblastic infiltrate in a leukemia patient receiving all-trans-retinoic acid therapy. J Am Acad Dermatol 1994;30:293–297. 2. Richard MA, Grob JJ, Laurans R et al. Sweet’s syndrome induced by granulocyte colony-stimulating factor in a woman with congenital neutropenia. J Am Acad Dermatol 1996;35:629–631. 3. Giasuddin AS, El-Orfi AH, Ziu MM et al. Sweet’s syndrome: is the pathogenesis mediated by helper T cell type 1 cytokines? J Am Acad Dermatol 1998;39:940–943. 4. Cohen PR. Sweet’s syndrome—a comprehensive review of an acute febrile neutrophilic dermatosis. Orphanet J Rare Dis 2007;2:34. 5. Cohen PR, Kurzrock R. Sweet’s syndrome: a review of current treatment options. Am J Clin Dermatol 2002;3:117–131. Oleg E. Akilov, M.D., Ph.D.* Nisha Desai, M.D.* Ronald Jaffe, M.B.B.Ch.† Robin P. Gehris, M.D.‡ *Department of Dermatology, University of Pittsburgh, Pittsburgh, Pennsylvania, †Division of Pediatric Pathology, Department of Pathology, University of Pittsburgh, Pittsburgh, Pennsylvania, ‡Division of Pediatric Dermatology, Children’s Hospital of Pittsburgh, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania Address correspondence to Robin P. Gehris, M.D., Children’s Dermatology Services, 11279 Perry Highway, Pine Center Suite 108, Wexford, PA 15090, or e-mail: [email protected].
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B
Bullous Sweet’s Syndrome After Granulocyte Colony-Stimulating Factor Therapy in a Child with Congenital Neutropenia Abstract: We present the case of a 20-month-old boy with congenital neutropenia for which he was being treated with granulocyte colony-stimulating factor (G-CSF) who developed bullous Sweet’s syndrome. Because of the challenging and extensive differential diagnosis of an acute bullous eruption in an immunocompromised child, we highlight the importance of a prompt and precise diagnosis before initiation of any systemic therapy in children with Sweet’s syndrome.
A 20-month-old Caucasian boy with a history of a genetic immunodeficiency was being treated with subcutaneous granulocyte colony-stimulating factor (G-CSF). His immunodeficiency was characterized by neutropenia, CD4+ lymphopenia, and hypogammaglobulinemia. He developed widespread symmetric, tender, flesh-colored to white, edematous coalescent plaques and tense bullae up to 1 cm in diameter on a noninflammatory background (Fig. 1A). The lesions were first noted on the back of his neck and then eventually spread to his extremities, sparing the trunk and ears. New lesions appeared at sites of intravenous injection. A review of systems was negative for any signs of infections. He continued to receive Pneumocystis jiroveci pneumonia prophylaxis with sulfamethoxazole and trimethoprim and fungal prophylaxis with itraconazole. Multiple blood and tissue cultures were negative for herpes simplex and varicella zoster viruses, bacteria, and fungi. Several skin biopsies revealed a spongiotic epidermis with a central collapsed vesicle containing neutrophils (Fig. 2). A confluent population of neutrophils surrounded the vessels and adnexa and extended throughout the dermis. No true leukocytoclastic vasculitis was appreciated. No viral inclusions were seen. No organisms were seen on periodic acid– Schiff or Grocott stains. Immunofluorescence was
DOI: 10.1111/pde.12282
© 2014 Wiley Periodicals, Inc.
Figure 1. (A) Generalized confluent, tense, painful bullae with mild hyperemic rims on the extensor surfaces of the lower extremities. (B) Rapid improvement 3 days after initiation of therapy with 0.5 mg/kg of oral prednisone.
negative for staining of immunoglobulin (Ig)A, IgG, and IgM. The patient was diagnosed with bullous Sweet’s syndrome and started on a 4-week course of oral prednisone at 2 mg/kg/day. G-CSF was suspected as a causative medication and was discontinued. He responded to this therapy with rapid clearing of the lesions as soon as day 3 after initiation of systemic steroids (Fig. 1B). Absolute neutropenia resolved while on steroids, whereas absolute lymphopenia remained unchanged. At the 1-month follow-up, the patient had only faintly erythematous round macules on his neck, back, chest, bilateral arms, hands, and legs. DISCUSSION Acute febrile neutrophilic dermatosis (Sweet’s syndrome) in children is most commonly idiopathic. Most often the precipitating event is a viral infection, with or without immunodeficiency. Many immunodeficient conditions associated with Sweet’s syndrome have been reported. Frequently the immunodeficient condition itself does not precipitate the Sweet’s syndrome. Rather, the treatment for this condition leads to an excess of neutrophils and induces differentiation and maturation of myeloid precursors, as observed in cases of retinoids (1) and G-CSF (2). It has been postulated that G-CSF-induced Sweet’s syndrome occurs when the number of neutrophils
e61
e62 Pediatric Dermatology Vol. 31 No. 2 March/April 2014
A
Systemic corticosteroids are the criterion standard of therapy for Sweet’s syndrome (4). Oral prednisone 0.5 to 1.5 mg/kg/day tapered over 6 weeks results in the rapid relief of systemic symptoms and skin lesions within 7 days (5), although the relapse rate (30%) is high, requiring the patient to have a prolonged course or an additional immunosuppressive agent. We present an uncommon bullous variant of Sweet’s syndrome in a child with congenital neutropenia who was receiving treatment with G-CSF. Prompt diagnosis based on multiple negative bacterial and viral cultures, the presence of pathergy phenomenon, and supportive histologic examination was crucial before the initiation of systemic corticosteroids, which resulted in a rapid improvement. REFERENCES
B
Figure 2. (A) Prominent papillary dermal edema and the formation of subepidermal bulla. (B) A dense neutrophilic infiltrate without evidence of primary leukocytoclastic vasculitis.
reaches some threshold at which cytokine dysregulation draws mature neutrophils into the skin (3).
1. Piette WW, Trapp JF, O’Donnell MJ et al. Acute neutrophilic dermatosis with myeloblastic infiltrate in a leukemia patient receiving all-trans-retinoic acid therapy. J Am Acad Dermatol 1994;30:293–297. 2. Richard MA, Grob JJ, Laurans R et al. Sweet’s syndrome induced by granulocyte colony-stimulating factor in a woman with congenital neutropenia. J Am Acad Dermatol 1996;35:629–631. 3. Giasuddin AS, El-Orfi AH, Ziu MM et al. Sweet’s syndrome: is the pathogenesis mediated by helper T cell type 1 cytokines? J Am Acad Dermatol 1998;39:940–943. 4. Cohen PR. Sweet’s syndrome—a comprehensive review of an acute febrile neutrophilic dermatosis. Orphanet J Rare Dis 2007;2:34. 5. Cohen PR, Kurzrock R. Sweet’s syndrome: a review of current treatment options. Am J Clin Dermatol 2002;3:117–131. Oleg E. Akilov, M.D., Ph.D.* Nisha Desai, M.D.* Ronald Jaffe, M.B.B.Ch.† Robin P. Gehris, M.D.‡ *Department of Dermatology, University of Pittsburgh, Pittsburgh, Pennsylvania, †Division of Pediatric Pathology, Department of Pathology, University of Pittsburgh, Pittsburgh, Pennsylvania, ‡Division of Pediatric Dermatology, Children’s Hospital of Pittsburgh, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania Address correspondence to Robin P. Gehris, M.D., Children’s Dermatology Services, 11279 Perry Highway, Pine Center Suite 108, Wexford, PA 15090, or e-mail: [email protected].
