Letters to the Editor
350
Ketoprofen-induced lamina lucida-type linear IgA bullous dermatosis
Figure 2 Skin biopsy (HES 9400) showing capillary thrombosis and eccrine ischaemia.
modify the natural course of the condition and improve prognosis, because tissue damage develops rapidly and is rarely fully reversible.3,4 Prevention is based on guidelines concerning the injection technique. They can reduce the risk of complication, but cannot eliminate this risk entirely. A. Almudimeegh,1 F. Le Pelletier,2 N. Dupin1,* ^pital Cochin, Service de 1Dermatologie, 2 d’anatomo-pathologie, Ho Paris Descartes, Paris, France APHP et Universite *Correspondence: N. Dupin. E-mail: [email protected]
References 1 Ezzedine K, Vadoud-Seyedi J, Heenen M. Nicolau syndrome following diclofenac administration. Br J Dermatol 2004; 150: 385–387. 2 Erkek E, Tuncez F, Sanli C et al. Nicolau’s syndrome in a newborn caused by triple DPT (diphtheria – tetanus – pertussis) vaccination. J Am Acad Dermatol 2006; 54: S241–S242. 3 Corazza M, Capozzi O, Virgili A. Five cases of livedo-like dermatitis (Nicolau’s syndrome) due to bismuth salts and various other non-steroidal antiinflammatory drugs. J Eur Acad Dermatol Venereol 2001; 15: 585–588. 4 Andrade P, Pereira N, Brites MM, Goncßalo M, Figueiredo A. Nicolau livedoid dermatitis following intramuscular benzathine penicillin injection. Dermatol Online J 2010; 16: 11. 5 Cherasse A, Kahn MF, Mistrih R, Maillard H, Strauss J, Tavernier C. Nicolau’s syndrome after local glucocorticoid injection. Joint Bone Spine 2003; 70: 390–392. 6 McGee AM, Davison PM. Skin necrosis following injection of non-steroidal anti-inflammatory drug. Br J Anaesth 2002; 88: 139–140. 7 Lee DP, Bae GY, Lee MW, Choi JH, Moon KC, Koh JK. Nicolau syndrome caused by piroxicam. Int J Dermatol 2005; 44: 1069–1070. 8 Faucher L, Marcoux D. What syndrome is this? Nicolau syndrome. Pediatr Dermatol 1995; 12: 187–190. 9 Guarneri C, Polimeni G. Nicolau syndrome following etanercept administration. Am J Clin Dermatol 2010; 11(Suppl. 1): 51–52. 10 Silva AM, Ton A, Loureiro TF, Agrizzi BL. Late development of Nicolau syndrome: case report. An Bras Dermatol 2011; 86: 157–159. DOI: 10.1111/jdv.12759
JEADV 2016, 30, 320–386
Editor Linear IgA bullous dermatosis (LABD) is a rare autoimmune subepidermal blistering disorder, characterized by deposited and circulating IgA anti-basement membrane zone (BMZ) antibodies.1–3 Clinical features overlap between bullous pemphigoid and dermatitis herpetiformis. In paediatric cases, skin lesions show typically clustered vesicles in herpetiform arrangement on buttocks and genital areas. In adult cases, in addition to characteristic annular erythemas with peripheral vesicles, polymorphic or atypical presentations have been described. LABD is usually idiopathic, but can be triggered by several medications, most frequently by vancomycin, but also by other drugs, including various antibiotic, non-steroid anti-inflammatory, anti-hypertensive and anti-epileptic drugs.3 However, there is no report of LABD induced by ketoprofen. A 52-year-old female, without significant medical history, was admitted in our hospital, complaining of erythema nodosumlike lesions bilaterally distributed in shins and ankles. She also had arthralgias, fever and malaise. A chest X-ray performed 3 weeks ago showed bilateral hiliar nodes. We suspected L€ ofgren syndrome. However, various laboratory tests, ECG, high resolution scanner, bronchoscopy, and functional respiratory tests showed no involvement of other organs. Ketoprofen 50 mg/day, omeprazole 20 mg/day and enoxaparin 40 mg/day were given subcutaneously. Seven days later, the patient developed lineally arranged vesicles and blisters with pruritus on the cubital fossae (Fig. 1). Well-defined erythematous maculo-papules with central crusts also appeared on the
Figure 1 Tense blisters and vesicles clustered on the cubital fossa.
© 2014 European Academy of Dermatology and Venereology
Letters to the Editor
Figure 2 Buttocks showing multiple well-defined erythematous maculo-papules with central crusts.
dorsal hands, wrists and buttocks (Fig. 2). The Nikolsky sign was not present. Mucous membranes were spared. Two biopsies were taken from the left buttock and left cubital fossa, which showed similar histopathological findings. Focal parakeratosis and intraepidermal pustules, as well as marked leucocytoclasis and some subepidermal vesicles, were observed. Direct immunofluorescence demonstrated linear IgA deposition to BMZ (Fig. 3). Indirect immunofluorescence using normal human skin did not show circulating IgG or IgA anti-BMZ antibodies. However, indirect immunofluorescence of 1M NaCl-split-skin showed positive IgA reactivity with epidermal side of the split. Immunoblotting of normal human epidermal extracts and recombinant proteins of BP180 NC16a and C-terminal domains showed
351
negative results for both IgG and IgA antibodies. IgA antibodies did not react with the 120-kDa LAD-1 in a concentrated culture supernatant of HaCaT-cells. The patient was diagnosed as lamina lucida-type LABD. Ketoprofen was replaced by acetylsalicylic acid, while omeprazole and enoxaparin were maintained. Medium power topical corticosteroids were administered and the skin lesions disappeared in less than 72 h. LABD shows 3 patterns of IgA deposit level; i.e., lamina lucida, sublamina densa and both locations.4,5 Most patients with the lamina lucida-type LABD show IgA autoantibodies to the 97-kDa LABD-97 and the 120-kDa LAD-1, which are extracellular domain fragments of BP180.4–6 Circulating autoantibodies are detected in less than 50% and the titres are typically low (1 : 10 to 1 : 80), therefore, negative results in indirect immunofluorescence does not exclude LABD.3,6,7 Pathomechanism in drug-induced LABD is still largely unknown. Drugs may cross-react with autoantigens in BMZ. Drugs may change conformational structure or unmask hidden antigens. Alternatively, drugs may break self-tolerance by the hapten-mediated process.7 As non-steroidal anti-inflammatory drugs related to LABD, piroxicam, diclofenac and naproxen were reported.3,8–10 As autoimmune bullous disease induced by ketoprofen, there is only one case of localized contact pemphigus.6 However, to the best of our knowledge, there is no report of ketoprofen-induced LABD. n,1,* S. Pe rez-Gala,1 G. Solano-Lo pez,1 M.J. Concha-Garzo 2 3 3 n1 J. Fraga, N. Ishii, T. Hashimoto, E. Daude 1
Department of Dermatology, Hospital Universitario La Princesa, Madrid, Spain, 2Department of Pathology, Hospital Universitario La Princesa, Madrid, Spain, 3Department of Dermatology, Kurume University School of Medicine and Kurume University Institute of Cutaneous Cell Biology, Fukuoka, Japan n. E-mail: [email protected] *Correspondence: M.J. Concha-Garzo
References
Figure 3 Direct immunofluorescence: IgA linear positivity on the basal layer.
JEADV 2016, 30, 320–386
1 Ingen-Housz-Oro S. Linear IgA bullous dermatosis: a review. Ann Dermatol Venereol 2011; 138: 214–220. 2 Gl€aser R, Sticherlin M. Successful treatment of linear IgA bullous dermatosis with mycophenolate mofetil. Acta Derm Venereol 2002; 82: 308–309. 3 Guide SV, Marinkovich MP. Linear IgA bullous dermatosis. Clin Dermatol 2001; 19: 719–727. 4 Ishii N, Ohyama B, Yamaguchi Z, Hashimoto T. IgA autoantibodies against the NC16a domain of BP180 but not 120-kDa LAD-1 detected in a patient with linear IgA disease. Br J Dermatol 2008; 158: 1151–1153. 5 Egan CA, Martineau MR, Taylor TB, Meyer LJ, Petersen MJ, Zone JJ. IgA antibodies recognizing LABD97 are predominantly IgA1 subclass. Acta Derm Venereol 1999; 79: 343–346. 6 Kanitakis J, Souillet AL, Faure M, Claudy A. Ketoprofen-induced pemphigus-like dermatosis: localized contact pemphigus? Acta Derm Venereol 2001; 81: 304–305. 7 Fortuna G, Marinkovich MP. Linear immunoglobulin A bullous dermatosis. Clin Dermatol 2012; 30: 38–50.
© 2014 European Academy of Dermatology and Venereology
352
8 Plunkett RW, Chiarello SE, Beutner EH. Linear IgA bullous dermatosis in one of two piroxicam-induced eruptions: A distinct direct immunofluorescence trend revealed by the literature. J Am Acad Dermatol 2001; 45: 691–696. 9 Camilleri M, Pace JL. Linear IgA bullous dermatosis induced by piroxicam. J Eur Acad Dermatol Venereol 1998; 10: 70–72. 10 Bouldin MB, Clowers-Webb HE, Davis JL, McEvoy MT, Davis MD. Naproxen-associated linear IgA bullous dermatosis: case report and review. Mayo Clin Proc 2000; 75: 967–970. DOI: 10.1111/jdv.12760
Penile calciphylaxis diagnosed with computed tomography Editor Calciphylaxis, or calcifying uraemic arteriopathy, is a rare and frequently fatal condition that is diagnosed in 4% of dialysis or kidney transplant patients with end-stage renal disease (ESRD). Early recognition of calciphylaxis is important, as it carries a 5-year mortality rate of 42% for proximal involvement and 72% for distal involvement.1 We describe a 60-year-old African American man was admitted for a tender pruritic penile plaque that had been growing for 2 weeks. Past medical history included ESRD, peripheral vascular disease, and calciphylaxis on his left forearm diagnosed 6 months prior to his current admission with a computed tomography (CT) scan that exhibited extensive soft tissue calcifi-
Figure 1 Necrotic plaque with surrounding erythema and oedema on the glans penis consistent with calciphylaxis.
JEADV 2016, 30, 320–386
Letters to the Editor
cation. After his initial diagnosis of calciphylaxis, he was treated with 25 g of intravenous sodium thiosulphate (STS) with dialysis three times weekly for 6 months, which resolved the calciphylaxis. This treatment was discontinued a few weeks prior to his current admission. Examination revealed a tender 1.5 cm 9 1.5 cm necrotic plaque with surrounding erythema and oedema of the glans penis (Fig. 1). Although a biopsy was considered to aid in diagnosis of the penile lesion, given the potential for significant morbidity with a biopsy at this site, the patient declined this procedure. Consequently, he was diagnosed with penile calciphylaxis based on history, physical exam and laboratory findings, as well as radiographic evaluation, which exhibited characteristic ‘net-like’ calcifications on plain film and CT scan (Fig. 2). Treatment was started with STS 25 g three times weekly during dialysis, and the penile lesion resolved within 5 months. Penile calciphylaxis is a rare manifestation of calciphylaxis.2 Mortality risk is 69% within 6 months, as penile calciphylaxis is a late clinical consequence of ESRD. Necrotic lesions of the penis are associated with a high risk of infection and subsequent sepsis.2,3 The gold standard for diagnosis of calciphylaxis is biopsy, as histopathologic findings are well known. However, consideration should be given for lesion location and patient comorbidities. Biopsy of a poorly vascularized area increases the risk for infection and poor wound healing.3 Diagnostic clues include the history and physical, laboratory values and imaging. In contrast to necrosis secondary to arterial insufficiency, calciphylaxis plaques are painful and develop rapidly, and distal peripheral pulses are typically present. Laboratory findings include low serum albumin and elevated parathyroid hormone, calcium and phosphate.3
Figure 2 CT scan demonstrating net-like calcifications in the subcutaneous tissue of the left arm.
© 2014 European Academy of Dermatology and Venereology
350
Ketoprofen-induced lamina lucida-type linear IgA bullous dermatosis
Figure 2 Skin biopsy (HES 9400) showing capillary thrombosis and eccrine ischaemia.
modify the natural course of the condition and improve prognosis, because tissue damage develops rapidly and is rarely fully reversible.3,4 Prevention is based on guidelines concerning the injection technique. They can reduce the risk of complication, but cannot eliminate this risk entirely. A. Almudimeegh,1 F. Le Pelletier,2 N. Dupin1,* ^pital Cochin, Service de 1Dermatologie, 2 d’anatomo-pathologie, Ho Paris Descartes, Paris, France APHP et Universite *Correspondence: N. Dupin. E-mail: [email protected]
References 1 Ezzedine K, Vadoud-Seyedi J, Heenen M. Nicolau syndrome following diclofenac administration. Br J Dermatol 2004; 150: 385–387. 2 Erkek E, Tuncez F, Sanli C et al. Nicolau’s syndrome in a newborn caused by triple DPT (diphtheria – tetanus – pertussis) vaccination. J Am Acad Dermatol 2006; 54: S241–S242. 3 Corazza M, Capozzi O, Virgili A. Five cases of livedo-like dermatitis (Nicolau’s syndrome) due to bismuth salts and various other non-steroidal antiinflammatory drugs. J Eur Acad Dermatol Venereol 2001; 15: 585–588. 4 Andrade P, Pereira N, Brites MM, Goncßalo M, Figueiredo A. Nicolau livedoid dermatitis following intramuscular benzathine penicillin injection. Dermatol Online J 2010; 16: 11. 5 Cherasse A, Kahn MF, Mistrih R, Maillard H, Strauss J, Tavernier C. Nicolau’s syndrome after local glucocorticoid injection. Joint Bone Spine 2003; 70: 390–392. 6 McGee AM, Davison PM. Skin necrosis following injection of non-steroidal anti-inflammatory drug. Br J Anaesth 2002; 88: 139–140. 7 Lee DP, Bae GY, Lee MW, Choi JH, Moon KC, Koh JK. Nicolau syndrome caused by piroxicam. Int J Dermatol 2005; 44: 1069–1070. 8 Faucher L, Marcoux D. What syndrome is this? Nicolau syndrome. Pediatr Dermatol 1995; 12: 187–190. 9 Guarneri C, Polimeni G. Nicolau syndrome following etanercept administration. Am J Clin Dermatol 2010; 11(Suppl. 1): 51–52. 10 Silva AM, Ton A, Loureiro TF, Agrizzi BL. Late development of Nicolau syndrome: case report. An Bras Dermatol 2011; 86: 157–159. DOI: 10.1111/jdv.12759
JEADV 2016, 30, 320–386
Editor Linear IgA bullous dermatosis (LABD) is a rare autoimmune subepidermal blistering disorder, characterized by deposited and circulating IgA anti-basement membrane zone (BMZ) antibodies.1–3 Clinical features overlap between bullous pemphigoid and dermatitis herpetiformis. In paediatric cases, skin lesions show typically clustered vesicles in herpetiform arrangement on buttocks and genital areas. In adult cases, in addition to characteristic annular erythemas with peripheral vesicles, polymorphic or atypical presentations have been described. LABD is usually idiopathic, but can be triggered by several medications, most frequently by vancomycin, but also by other drugs, including various antibiotic, non-steroid anti-inflammatory, anti-hypertensive and anti-epileptic drugs.3 However, there is no report of LABD induced by ketoprofen. A 52-year-old female, without significant medical history, was admitted in our hospital, complaining of erythema nodosumlike lesions bilaterally distributed in shins and ankles. She also had arthralgias, fever and malaise. A chest X-ray performed 3 weeks ago showed bilateral hiliar nodes. We suspected L€ ofgren syndrome. However, various laboratory tests, ECG, high resolution scanner, bronchoscopy, and functional respiratory tests showed no involvement of other organs. Ketoprofen 50 mg/day, omeprazole 20 mg/day and enoxaparin 40 mg/day were given subcutaneously. Seven days later, the patient developed lineally arranged vesicles and blisters with pruritus on the cubital fossae (Fig. 1). Well-defined erythematous maculo-papules with central crusts also appeared on the
Figure 1 Tense blisters and vesicles clustered on the cubital fossa.
© 2014 European Academy of Dermatology and Venereology
Letters to the Editor
Figure 2 Buttocks showing multiple well-defined erythematous maculo-papules with central crusts.
dorsal hands, wrists and buttocks (Fig. 2). The Nikolsky sign was not present. Mucous membranes were spared. Two biopsies were taken from the left buttock and left cubital fossa, which showed similar histopathological findings. Focal parakeratosis and intraepidermal pustules, as well as marked leucocytoclasis and some subepidermal vesicles, were observed. Direct immunofluorescence demonstrated linear IgA deposition to BMZ (Fig. 3). Indirect immunofluorescence using normal human skin did not show circulating IgG or IgA anti-BMZ antibodies. However, indirect immunofluorescence of 1M NaCl-split-skin showed positive IgA reactivity with epidermal side of the split. Immunoblotting of normal human epidermal extracts and recombinant proteins of BP180 NC16a and C-terminal domains showed
351
negative results for both IgG and IgA antibodies. IgA antibodies did not react with the 120-kDa LAD-1 in a concentrated culture supernatant of HaCaT-cells. The patient was diagnosed as lamina lucida-type LABD. Ketoprofen was replaced by acetylsalicylic acid, while omeprazole and enoxaparin were maintained. Medium power topical corticosteroids were administered and the skin lesions disappeared in less than 72 h. LABD shows 3 patterns of IgA deposit level; i.e., lamina lucida, sublamina densa and both locations.4,5 Most patients with the lamina lucida-type LABD show IgA autoantibodies to the 97-kDa LABD-97 and the 120-kDa LAD-1, which are extracellular domain fragments of BP180.4–6 Circulating autoantibodies are detected in less than 50% and the titres are typically low (1 : 10 to 1 : 80), therefore, negative results in indirect immunofluorescence does not exclude LABD.3,6,7 Pathomechanism in drug-induced LABD is still largely unknown. Drugs may cross-react with autoantigens in BMZ. Drugs may change conformational structure or unmask hidden antigens. Alternatively, drugs may break self-tolerance by the hapten-mediated process.7 As non-steroidal anti-inflammatory drugs related to LABD, piroxicam, diclofenac and naproxen were reported.3,8–10 As autoimmune bullous disease induced by ketoprofen, there is only one case of localized contact pemphigus.6 However, to the best of our knowledge, there is no report of ketoprofen-induced LABD. n,1,* S. Pe rez-Gala,1 G. Solano-Lo pez,1 M.J. Concha-Garzo 2 3 3 n1 J. Fraga, N. Ishii, T. Hashimoto, E. Daude 1
Department of Dermatology, Hospital Universitario La Princesa, Madrid, Spain, 2Department of Pathology, Hospital Universitario La Princesa, Madrid, Spain, 3Department of Dermatology, Kurume University School of Medicine and Kurume University Institute of Cutaneous Cell Biology, Fukuoka, Japan n. E-mail: [email protected] *Correspondence: M.J. Concha-Garzo
References
Figure 3 Direct immunofluorescence: IgA linear positivity on the basal layer.
JEADV 2016, 30, 320–386
1 Ingen-Housz-Oro S. Linear IgA bullous dermatosis: a review. Ann Dermatol Venereol 2011; 138: 214–220. 2 Gl€aser R, Sticherlin M. Successful treatment of linear IgA bullous dermatosis with mycophenolate mofetil. Acta Derm Venereol 2002; 82: 308–309. 3 Guide SV, Marinkovich MP. Linear IgA bullous dermatosis. Clin Dermatol 2001; 19: 719–727. 4 Ishii N, Ohyama B, Yamaguchi Z, Hashimoto T. IgA autoantibodies against the NC16a domain of BP180 but not 120-kDa LAD-1 detected in a patient with linear IgA disease. Br J Dermatol 2008; 158: 1151–1153. 5 Egan CA, Martineau MR, Taylor TB, Meyer LJ, Petersen MJ, Zone JJ. IgA antibodies recognizing LABD97 are predominantly IgA1 subclass. Acta Derm Venereol 1999; 79: 343–346. 6 Kanitakis J, Souillet AL, Faure M, Claudy A. Ketoprofen-induced pemphigus-like dermatosis: localized contact pemphigus? Acta Derm Venereol 2001; 81: 304–305. 7 Fortuna G, Marinkovich MP. Linear immunoglobulin A bullous dermatosis. Clin Dermatol 2012; 30: 38–50.
© 2014 European Academy of Dermatology and Venereology
352
8 Plunkett RW, Chiarello SE, Beutner EH. Linear IgA bullous dermatosis in one of two piroxicam-induced eruptions: A distinct direct immunofluorescence trend revealed by the literature. J Am Acad Dermatol 2001; 45: 691–696. 9 Camilleri M, Pace JL. Linear IgA bullous dermatosis induced by piroxicam. J Eur Acad Dermatol Venereol 1998; 10: 70–72. 10 Bouldin MB, Clowers-Webb HE, Davis JL, McEvoy MT, Davis MD. Naproxen-associated linear IgA bullous dermatosis: case report and review. Mayo Clin Proc 2000; 75: 967–970. DOI: 10.1111/jdv.12760
Penile calciphylaxis diagnosed with computed tomography Editor Calciphylaxis, or calcifying uraemic arteriopathy, is a rare and frequently fatal condition that is diagnosed in 4% of dialysis or kidney transplant patients with end-stage renal disease (ESRD). Early recognition of calciphylaxis is important, as it carries a 5-year mortality rate of 42% for proximal involvement and 72% for distal involvement.1 We describe a 60-year-old African American man was admitted for a tender pruritic penile plaque that had been growing for 2 weeks. Past medical history included ESRD, peripheral vascular disease, and calciphylaxis on his left forearm diagnosed 6 months prior to his current admission with a computed tomography (CT) scan that exhibited extensive soft tissue calcifi-
Figure 1 Necrotic plaque with surrounding erythema and oedema on the glans penis consistent with calciphylaxis.
JEADV 2016, 30, 320–386
Letters to the Editor
cation. After his initial diagnosis of calciphylaxis, he was treated with 25 g of intravenous sodium thiosulphate (STS) with dialysis three times weekly for 6 months, which resolved the calciphylaxis. This treatment was discontinued a few weeks prior to his current admission. Examination revealed a tender 1.5 cm 9 1.5 cm necrotic plaque with surrounding erythema and oedema of the glans penis (Fig. 1). Although a biopsy was considered to aid in diagnosis of the penile lesion, given the potential for significant morbidity with a biopsy at this site, the patient declined this procedure. Consequently, he was diagnosed with penile calciphylaxis based on history, physical exam and laboratory findings, as well as radiographic evaluation, which exhibited characteristic ‘net-like’ calcifications on plain film and CT scan (Fig. 2). Treatment was started with STS 25 g three times weekly during dialysis, and the penile lesion resolved within 5 months. Penile calciphylaxis is a rare manifestation of calciphylaxis.2 Mortality risk is 69% within 6 months, as penile calciphylaxis is a late clinical consequence of ESRD. Necrotic lesions of the penis are associated with a high risk of infection and subsequent sepsis.2,3 The gold standard for diagnosis of calciphylaxis is biopsy, as histopathologic findings are well known. However, consideration should be given for lesion location and patient comorbidities. Biopsy of a poorly vascularized area increases the risk for infection and poor wound healing.3 Diagnostic clues include the history and physical, laboratory values and imaging. In contrast to necrosis secondary to arterial insufficiency, calciphylaxis plaques are painful and develop rapidly, and distal peripheral pulses are typically present. Laboratory findings include low serum albumin and elevated parathyroid hormone, calcium and phosphate.3
Figure 2 CT scan demonstrating net-like calcifications in the subcutaneous tissue of the left arm.
© 2014 European Academy of Dermatology and Venereology
