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Mucocutaneous involvement in newborn with congenital epidermolysis bullosa acquisita
3170
3314
Laryngeal involvement in paraneoplastic pemphigus associated with benign Brenner tumor Helena Rocchetto, MD, Departamento de Dermatologia do Hospital das Clınicas HCFMUSP, S~ao Paulo, Brazil; Denise Miyamoto, MD, Departamento de Dermatologia do Hospital das Clınicas -HCFMUSP, S~ao Paulo, Brazil; Valeria Aoki, MD, PhD, Departamento de Dermatologia do Hospital das Clınicas HCFMUSP, S~ao Paulo, Brazil; Celina Wakisaka Maruta, MD, PhD, Departamento de Dermatologia do Hospital das Clınicas -HCFMUSP, S~ao Paulo, Brazil; Claudia Giuli Santi, MD, PhD, Departamento de Dermatologia do Hospital das Clınicas HCFMUSP, S~ao Paulo, Brazil
Mucocutaneous involvement in newborn with congenital epidermolysis bullosa acquisita Paula Yume Sato Serzedello Corr^ea, MD, Hospital das Clınicas da Faculdade de Medicina da Universidade de S~ao Paulo, S~ao Paulo, Brazil; Denise Miyamoto, MD, Hospital das Clınicas da Faculdade de Medicina da Universidade de S~ao Paulo, S~ao Paulo, Brazil; Celina Wakisaka Maruta, PhD, Hospital das Clınicas da Faculdade de Medicina da Universidade de S~ao Paulo, S~ao Paulo, Brazil; Valeria Aoki, PhD, Hospital das Clınicas da Faculdade de Medicina da Universidade de S~ao Paulo, S~ao Paulo, Brazil; Claudia Giuli Santi, PhD, Hospital das Clınicas da Faculdade de Medicina da Universidade de S~ao Paulo, S~ao Paulo, Brazil
Introduction: Paraneoplastic pemphigus (PNP), a distinct autoimmune blistering disorder with underlying neoplasia, was first described in 1990 by Anhalt et al. PNP is usually associated with hematologic malignancy, although correlated solid tumors were described in nearly 15% of the cases. Polymorphic cutaneous lesions may resemble pemphigus vulgaris, erythema multiforme, bullous pemphigoid, lichen planus and graft-versus-host disease. Oral, ocular and genital mucosa are predominantly affected, and laryngeal manifestation is exceptional. We report a PNP case with exuberant laryngeal involvement associated with benign Brenner tumor.
Background: Epidermolysis bullosa acquisita (EBA) is a rare subepidermal bullous dermatosis with autoantibodies against type VII collagen, the main component of anchoring fibrils. EBA onset commonly occurs between 40 and 60 years of age, although cases during childhood have been described. Only one case of congenital EBA has been reported. We describe a second newborn with congenital EBA mucocutaneous lesions. Case report: A 25-year-old patient with EBA, receiving low dose prednisone, delivered a white female newborn with erosions on the scalp, nose, upper lip, tongue and limbs. A skin biopsy was performed at the right thigh: histopathologic analysis showed a subepidermal blister with neutrophils; direct immunofluorescence microscopy of perilesional skin exhibited IgG, IgM, and C3 deposits at the basement membrane zone. Serum IgG antibodies were bound to the dermal side of the cleavage in indirect immunofluorescence microscopy on salt-split skin; detection of serum antibodies against noncollagenous domain 1 of type VII collagen by ELISA is under analysis. These findings corroborated the hypothesis of congenital EBA and after approximately 3 months of supportive care, lesions completely healed with multiple milia. No recurrence was observed.
Case report: A 55-year-old female patient presented a 2-year history of brownish keratotic plaques on the trunk and limbs and violaceous papules on the face and neck. She also had conjunctival hyperemia and oral erosions with intense hoarseness. Ophthalmologic evaluation reported conjunctival erosions; nasofibroscopy revealed blisters at the laryngeal face of epiglottis. Due to benign Brenner tumor diagnosis, bilateral adnexectomy had been performed 6 months before referral to our clinic. A biopsy from left arm was obtained: histopathologic analysis showed apoptotic keratinocytes and lichenoid interface dermatitis. As she developed blisters on the face and palate with dysphagia and odynophagia, a biopsy from the palate was performed. Histopathologic evaluation exhibited apoptotic keratinocytes and a lymphoplasmacytic infiltrate at the lamina propria; direct immunofluorescence (IF) demonstrated IgG intercellular deposits at the epidermis, and IgG and C3 bound to the basement membrane zone. Indirect IF with rat bladder epithelium as substrate is under analysis. These findings suggested the diagnosis of PNP. She was submitted to a complete neoplasia screening, and no other tumor was found. Treatment with prednisone 1 mg/kg/day and azathioprine 150 mg/day was introduced with improvement of the lesions. Discussion: In our case, PNP onset preceded the diagnosis of the neoplasia, and persisted despite of complete surgical removal of the tumor. Besides, mucosal involvement may contribute to morbidity related to PNP and require sustained immunosuppressive therapy for adequate control. Conclusion: To our knowledge, this is the first case of PNP in association with benign Brenner tumor. Multidisciplinary evaluation and follow-up is recommended to determine the degree of mucosal involvement, and adjust therapy.
Discussion: Neonatal autoimmune bullous disease may be attributed to placental transfer of maternal autoantibodies influenced by hormonal changes during pregnancy. In experimental EBA mice models, serum levels of pathogenic type VII collagen antibodies were comparable in neonatal offspring and maternal mouse immediately after birth. On the previous report of congenital EBA, no new lesions developed after 10 days of life, earlier than the patient described on our case, who presented new erosions until 45 days of age. Although plasmatic IgG half-life is approximately 14 days in human adult, skin-bound IgG against type VII collagen may still be detectable after 8 weeks in neonatal offspring of maternal mice with EBA. Conclusion: To the best of our knowledge, our patient is the first case of congenital EBA with mucocutaneous lesions. Similar to the previous case, she improved without systemic treatment, and no complications were observed. Prolonged supportive care and follow-up may be recommended as delayed clinical remission might occur due to persistence of tissue-bound maternal autoantibodies. Commercial support: None identified.
Commercial support: None identified.
3603 Neutrophilic dermatosis of the hands: Case report Ticiana Stumpf, MD, Santa Casa de Misericordia de Porto Alegre, Porto Alegre, Brazil; Fernanda Bonkevitch, MD, Santa Casa de Misericordia de Porto Alegre, Porto Alegre, Brazil; Gabriela Mosena, MD, Santa Casa de Misericordia de Porto Alegre, Porto Alegre, Brazil; Mariana Ferreira, MD, Santa Casa de Misericordia de Porto Alegre, Porto Alegre, Brazil; Camila Rodrigues, MD, Santa Casa de Misericordia de Porto Alegre, Porto Alegre, Brazil; Gerson Vettorato, MD, MD, Santa Casa de Misericordia de Porto Alegre, Porto Alegre, Brazil
MuckleeWells syndrome (MWS) is a rare autosomal dominant disease caused by a heterozygous mutation on chromosome 1q44 affecting the NLRP3 (CIAS1) gene responsible for cryopyrin encodement. The NALP3 inflammasome complex utilizes cryopyrin as scaffolding for the promotion, activation and amplification of proinflammatory cytokines IL-1b and IL-18 responsible for the induction and maintenance of inflammation. Cryopyrin hyperactivity produces the classic clinical triad of urticaria, episodic fevers and sensorineural deafness, as displayed in MWS. Additionally, renal amyloidosis resulting in proteinuria and chronic renal insufficiency will occur in 25% of patients. We present a case of a female in her mid-30s with a transient urticarial eruption on her bilateral upper extremities, chest and back with associated recurrent low-grade fevers, eye redness and arthralgia present for approximately 20 years. Cold temperatures and stress exacerbated these symptoms. The patient also complained of new onset hearing loss with associated tinnitus. A family history of similar symptoms was present in her brother, mother and maternal grandmother. Laboratory examination revealed an elevated CRP. Protein electrophoresis demonstrated beta-gamma bridging with an increased IgA and polyclonal gamma globulins. Further examination findings were within normal limits. Genetic evaluation confirmed a diagnosis of MWS. Treatment with an IL-1 receptor antagonist has demonstrated vast improvement of her clinical symptoms. Early identification and treatment of MWS is key to delaying disease progression.
Neutrophilic dermatosis of the hands (NDH) is a rare disease with about 60 cases being described in literature. The exclusive involvement of hands is characteristic, which differentiates from Sweet syndrome and pyoderma gangrenosum. Having been described by Strutton et al in 1995 as pustular vasculitis of the dorsal hands (considered a variant of Sweet syndrome) it received its current denomination in 2000 by Galaria et al, and in the last few years it has been considered a distinct entity. A case report is presented below. A 49-year-old female of African descent diagnosed with rheumatoid arthritis five years ago (in use of 15 mg of methotrexate a week) came to us complaining about having asymptomatic lesions in her hands for two months. On examination there was a noninfiltrated erythematous plaques with undefined papulous edge on the dorsal of the hands. Biopsy was compatible with neutrophilic dermatosis. After topic application of corticotherapy with betamethasone for 10 days there was full remission of lesions. NDH manifests itself with papules, plaques, pustules, blisters and ulcerations, usually limited to the dorsal of hands and it can less often involve the palm area. It mostly attacks female patients (69%), and the average age is 62. There may be association with hematologic neoplasia (27% of cases) and inflammatory bowel disease (15%). Most of them present fever, leukocytosis and/or HSV increase and C-reactive protein. It is seldom associated with rheumatoid arthritis and other neoplasias. There were also demonstrations of associations with hepatitis C and sarcoidosis, and it does not seem to be inducted by drugs. In the histopathologic examination, there were infiltrated neutrophils in the reticular and papillary dermis, together with spongiosis, with the possibility of having intraepidermal pustules. Vasculitis is found in 22-28% of older injuries, which is a result of the release of toxic products by the neutrophils, with no immunological ground. In almost all cases described, there was a good response to the use of systemic corticosteroids with a dose of 1 mg per kilogram per day. Rarely, and in less extensive cases, topical corticosteroids or tacrolimus can be used. Spontaneous remission is rare. In case of relapse, dapsone and colchicine can be associated. Cyclosporin, azathioprine, methotrexate, indomethacin, and minocycline are cited less frequently.
Commercial support: None identified.
Commercial support: None identified.
3325 MuckleeWells syndrome: A rare cryopyrinopathy Monica Van Acker, DO, St. Joseph Mercy Hospital, Ypsilanti, MI, United States; David Fivenson, MD, St. Joseph Mercy Hospital, Ypsilanti, MI, United States
MAY 2016
J AM ACAD DERMATOL
AB147
3314
Laryngeal involvement in paraneoplastic pemphigus associated with benign Brenner tumor Helena Rocchetto, MD, Departamento de Dermatologia do Hospital das Clınicas HCFMUSP, S~ao Paulo, Brazil; Denise Miyamoto, MD, Departamento de Dermatologia do Hospital das Clınicas -HCFMUSP, S~ao Paulo, Brazil; Valeria Aoki, MD, PhD, Departamento de Dermatologia do Hospital das Clınicas HCFMUSP, S~ao Paulo, Brazil; Celina Wakisaka Maruta, MD, PhD, Departamento de Dermatologia do Hospital das Clınicas -HCFMUSP, S~ao Paulo, Brazil; Claudia Giuli Santi, MD, PhD, Departamento de Dermatologia do Hospital das Clınicas HCFMUSP, S~ao Paulo, Brazil
Mucocutaneous involvement in newborn with congenital epidermolysis bullosa acquisita Paula Yume Sato Serzedello Corr^ea, MD, Hospital das Clınicas da Faculdade de Medicina da Universidade de S~ao Paulo, S~ao Paulo, Brazil; Denise Miyamoto, MD, Hospital das Clınicas da Faculdade de Medicina da Universidade de S~ao Paulo, S~ao Paulo, Brazil; Celina Wakisaka Maruta, PhD, Hospital das Clınicas da Faculdade de Medicina da Universidade de S~ao Paulo, S~ao Paulo, Brazil; Valeria Aoki, PhD, Hospital das Clınicas da Faculdade de Medicina da Universidade de S~ao Paulo, S~ao Paulo, Brazil; Claudia Giuli Santi, PhD, Hospital das Clınicas da Faculdade de Medicina da Universidade de S~ao Paulo, S~ao Paulo, Brazil
Introduction: Paraneoplastic pemphigus (PNP), a distinct autoimmune blistering disorder with underlying neoplasia, was first described in 1990 by Anhalt et al. PNP is usually associated with hematologic malignancy, although correlated solid tumors were described in nearly 15% of the cases. Polymorphic cutaneous lesions may resemble pemphigus vulgaris, erythema multiforme, bullous pemphigoid, lichen planus and graft-versus-host disease. Oral, ocular and genital mucosa are predominantly affected, and laryngeal manifestation is exceptional. We report a PNP case with exuberant laryngeal involvement associated with benign Brenner tumor.
Background: Epidermolysis bullosa acquisita (EBA) is a rare subepidermal bullous dermatosis with autoantibodies against type VII collagen, the main component of anchoring fibrils. EBA onset commonly occurs between 40 and 60 years of age, although cases during childhood have been described. Only one case of congenital EBA has been reported. We describe a second newborn with congenital EBA mucocutaneous lesions. Case report: A 25-year-old patient with EBA, receiving low dose prednisone, delivered a white female newborn with erosions on the scalp, nose, upper lip, tongue and limbs. A skin biopsy was performed at the right thigh: histopathologic analysis showed a subepidermal blister with neutrophils; direct immunofluorescence microscopy of perilesional skin exhibited IgG, IgM, and C3 deposits at the basement membrane zone. Serum IgG antibodies were bound to the dermal side of the cleavage in indirect immunofluorescence microscopy on salt-split skin; detection of serum antibodies against noncollagenous domain 1 of type VII collagen by ELISA is under analysis. These findings corroborated the hypothesis of congenital EBA and after approximately 3 months of supportive care, lesions completely healed with multiple milia. No recurrence was observed.
Case report: A 55-year-old female patient presented a 2-year history of brownish keratotic plaques on the trunk and limbs and violaceous papules on the face and neck. She also had conjunctival hyperemia and oral erosions with intense hoarseness. Ophthalmologic evaluation reported conjunctival erosions; nasofibroscopy revealed blisters at the laryngeal face of epiglottis. Due to benign Brenner tumor diagnosis, bilateral adnexectomy had been performed 6 months before referral to our clinic. A biopsy from left arm was obtained: histopathologic analysis showed apoptotic keratinocytes and lichenoid interface dermatitis. As she developed blisters on the face and palate with dysphagia and odynophagia, a biopsy from the palate was performed. Histopathologic evaluation exhibited apoptotic keratinocytes and a lymphoplasmacytic infiltrate at the lamina propria; direct immunofluorescence (IF) demonstrated IgG intercellular deposits at the epidermis, and IgG and C3 bound to the basement membrane zone. Indirect IF with rat bladder epithelium as substrate is under analysis. These findings suggested the diagnosis of PNP. She was submitted to a complete neoplasia screening, and no other tumor was found. Treatment with prednisone 1 mg/kg/day and azathioprine 150 mg/day was introduced with improvement of the lesions. Discussion: In our case, PNP onset preceded the diagnosis of the neoplasia, and persisted despite of complete surgical removal of the tumor. Besides, mucosal involvement may contribute to morbidity related to PNP and require sustained immunosuppressive therapy for adequate control. Conclusion: To our knowledge, this is the first case of PNP in association with benign Brenner tumor. Multidisciplinary evaluation and follow-up is recommended to determine the degree of mucosal involvement, and adjust therapy.
Discussion: Neonatal autoimmune bullous disease may be attributed to placental transfer of maternal autoantibodies influenced by hormonal changes during pregnancy. In experimental EBA mice models, serum levels of pathogenic type VII collagen antibodies were comparable in neonatal offspring and maternal mouse immediately after birth. On the previous report of congenital EBA, no new lesions developed after 10 days of life, earlier than the patient described on our case, who presented new erosions until 45 days of age. Although plasmatic IgG half-life is approximately 14 days in human adult, skin-bound IgG against type VII collagen may still be detectable after 8 weeks in neonatal offspring of maternal mice with EBA. Conclusion: To the best of our knowledge, our patient is the first case of congenital EBA with mucocutaneous lesions. Similar to the previous case, she improved without systemic treatment, and no complications were observed. Prolonged supportive care and follow-up may be recommended as delayed clinical remission might occur due to persistence of tissue-bound maternal autoantibodies. Commercial support: None identified.
Commercial support: None identified.
3603 Neutrophilic dermatosis of the hands: Case report Ticiana Stumpf, MD, Santa Casa de Misericordia de Porto Alegre, Porto Alegre, Brazil; Fernanda Bonkevitch, MD, Santa Casa de Misericordia de Porto Alegre, Porto Alegre, Brazil; Gabriela Mosena, MD, Santa Casa de Misericordia de Porto Alegre, Porto Alegre, Brazil; Mariana Ferreira, MD, Santa Casa de Misericordia de Porto Alegre, Porto Alegre, Brazil; Camila Rodrigues, MD, Santa Casa de Misericordia de Porto Alegre, Porto Alegre, Brazil; Gerson Vettorato, MD, MD, Santa Casa de Misericordia de Porto Alegre, Porto Alegre, Brazil
MuckleeWells syndrome (MWS) is a rare autosomal dominant disease caused by a heterozygous mutation on chromosome 1q44 affecting the NLRP3 (CIAS1) gene responsible for cryopyrin encodement. The NALP3 inflammasome complex utilizes cryopyrin as scaffolding for the promotion, activation and amplification of proinflammatory cytokines IL-1b and IL-18 responsible for the induction and maintenance of inflammation. Cryopyrin hyperactivity produces the classic clinical triad of urticaria, episodic fevers and sensorineural deafness, as displayed in MWS. Additionally, renal amyloidosis resulting in proteinuria and chronic renal insufficiency will occur in 25% of patients. We present a case of a female in her mid-30s with a transient urticarial eruption on her bilateral upper extremities, chest and back with associated recurrent low-grade fevers, eye redness and arthralgia present for approximately 20 years. Cold temperatures and stress exacerbated these symptoms. The patient also complained of new onset hearing loss with associated tinnitus. A family history of similar symptoms was present in her brother, mother and maternal grandmother. Laboratory examination revealed an elevated CRP. Protein electrophoresis demonstrated beta-gamma bridging with an increased IgA and polyclonal gamma globulins. Further examination findings were within normal limits. Genetic evaluation confirmed a diagnosis of MWS. Treatment with an IL-1 receptor antagonist has demonstrated vast improvement of her clinical symptoms. Early identification and treatment of MWS is key to delaying disease progression.
Neutrophilic dermatosis of the hands (NDH) is a rare disease with about 60 cases being described in literature. The exclusive involvement of hands is characteristic, which differentiates from Sweet syndrome and pyoderma gangrenosum. Having been described by Strutton et al in 1995 as pustular vasculitis of the dorsal hands (considered a variant of Sweet syndrome) it received its current denomination in 2000 by Galaria et al, and in the last few years it has been considered a distinct entity. A case report is presented below. A 49-year-old female of African descent diagnosed with rheumatoid arthritis five years ago (in use of 15 mg of methotrexate a week) came to us complaining about having asymptomatic lesions in her hands for two months. On examination there was a noninfiltrated erythematous plaques with undefined papulous edge on the dorsal of the hands. Biopsy was compatible with neutrophilic dermatosis. After topic application of corticotherapy with betamethasone for 10 days there was full remission of lesions. NDH manifests itself with papules, plaques, pustules, blisters and ulcerations, usually limited to the dorsal of hands and it can less often involve the palm area. It mostly attacks female patients (69%), and the average age is 62. There may be association with hematologic neoplasia (27% of cases) and inflammatory bowel disease (15%). Most of them present fever, leukocytosis and/or HSV increase and C-reactive protein. It is seldom associated with rheumatoid arthritis and other neoplasias. There were also demonstrations of associations with hepatitis C and sarcoidosis, and it does not seem to be inducted by drugs. In the histopathologic examination, there were infiltrated neutrophils in the reticular and papillary dermis, together with spongiosis, with the possibility of having intraepidermal pustules. Vasculitis is found in 22-28% of older injuries, which is a result of the release of toxic products by the neutrophils, with no immunological ground. In almost all cases described, there was a good response to the use of systemic corticosteroids with a dose of 1 mg per kilogram per day. Rarely, and in less extensive cases, topical corticosteroids or tacrolimus can be used. Spontaneous remission is rare. In case of relapse, dapsone and colchicine can be associated. Cyclosporin, azathioprine, methotrexate, indomethacin, and minocycline are cited less frequently.
Commercial support: None identified.
Commercial support: None identified.
3325 MuckleeWells syndrome: A rare cryopyrinopathy Monica Van Acker, DO, St. Joseph Mercy Hospital, Ypsilanti, MI, United States; David Fivenson, MD, St. Joseph Mercy Hospital, Ypsilanti, MI, United States
MAY 2016
J AM ACAD DERMATOL
AB147