Acquired cutis laxa secondary to acute generalized exanthematous pustulosis: A case report and mini-review of literature.

Cutis laxa presents as loose redundant skin folds and loss of dermal elastic tissue. Acquired cutis laxa (ACL) is characterized by later onset. It has been reported in association with various kinds of neutrophilic dermatoses, drugs, metabolic disorders, and autoimmune disorders. Acute generalized exanthematous pustulosis (AGEP) is usually classified as a severe cutaneous adverse reaction characterized by T cell-mediated neutrophilic inflammation. We previously reported a mild case of AGEP caused by gemcitabine in a 76-year-old man. Here, we report a case of ACL secondary to AGEP in this patient. He developed AGEP 8 days after gemcitabine administration. Four weeks after beginning chemotherapy, his skin had become atrophic, loose, and darkly pigmented in areas previously affected by AGEP. Histopathological examination revealed edema and perivascular lymphocytic infiltration but no neutrophilic infiltration in the upper dermis. Elastica van Gieson staining showed that the elastic fibers in all layers of the dermis were sparse and shortened. Electron microscopy showed elevated numbers of fibroblasts and altered elastic fibers with irregular surfaces. Finally, he was diagnosed with ACL secondary to AGEP. He was treated with topical corticosteroids and oral antihistamines. Skin atrophy decreased over 3 months. We summarize 36 cases (including our case) with ACL secondary to neutrophilic dermatosis. We discuss these clinical manifestations, causative neutrophilic disorders, treatments, and outcomes. The mean age of patients was 3.5 years. Five patients had an aortic lesion as systemic involvement. The most common causative neutrophilic disorders were Sweet syndrome (24 cases), followed by urticaria-like neutrophilic dermatosis (11 cases). There were no cases of AGEP except for our case. Although treatment for ACL secondary to neutrophilic dermatosis, such as dapsone, oral prednisolone, adalimumab, and plastic surgery were reported, ACL is generally refractory and irreversible. Our patient was considered reversibly cured due to the absence of continuous neutrophil-mediated elastolysis.

Autoantibodies to BPAG1e Trigger Experimental Bullous Pemphigoid in Mice.

Bullous pemphigoid (BP) is an autoimmune blistering disease that targets the hemidesmosomal proteins BP180 and BP230/BPAG1e. Whereas the role of anti-BP180 antibodies has been extensively characterized, the pathogenicity of anti-BPAG1e antibodies remains unclear. The purpose of this study is to elucidate the role of antibodies to BPAG1e in the experimental bullous pemphigoid models. We generated Bpag1 conditional knockout mice, where the knockout of Bpag1 is restricted to keratin 5-expressing epithelial cells. Bpag1 conditional knockout mice were immunized with the C-terminal portion of BPAG1e, and the splenocytes were injected into Rag2-/- mice intravenously. The recipient mice presented with erosion on the feet and tails. Microscopic examination showed subepidermal blisters and a linear deposition of IgG at the dermal-epidermal junction. To assess the potential role of trauma on BP development, we inflicted surface wounds on the dorsum of the Rag2-/- recipient mice after adoptive transfer. The wounded Rag2-/- mice had increased morbidity and severity of BP-like symptoms. Moreover, the depletion of B cells from splenocytes abolished a subepidermal blistering phenotype in vivo. These findings demonstrate that antibodies to BPAG1e might play a pathogenic role in causing subepidermal blistering, and external factors, including trauma, might be a trigger for BP development.

Trichoscopic Findings of Erosive Pustular Dermatosis of the Scalp Associated with Gefitinib.

Alopecia associated with epidermal growth factor receptor (EGFR) inhibitor therapy is a rare cutaneous side effect with the potential to progress to scarring alopecia. Thus, dermatologists should make an early diagnosis. We present the case of a 57-year-old Japanese female with scarring alopecia associated with gefitinib, which is an EGFR inhibitor, including trichoscopic findings. The patient treated with gefitinib for non-small cell lung cancer experienced skin rash and hair loss of the scalp. The scalp lesions appeared similar to erosive pustular dermatosis of the scalp. Trichoscopic examination showed follicular keratotic plugging, milky red areas, white patches, hair shaft disorder, tapering hair, and absence of follicular opening. Histological examination showed ruptured hair follicles with a perifollicular infiltration of plasma cells, lymphocytes, and histiocytes. Oral minocycline and topical steroid treatment produced no improvement. With a reduction in the gefitinib dosage, alopecia gradually improved, although scarring remained. We consider these trichoscopic findings and suspect that follicular keratotic plugging might be a finding associated with scarring alopecia due to EGFR inhibitor therapy.