Epidermodysplasia verruciformis-associated eccrine neoplasm: a rare entity with distinctive clinical and histopathologic features.

Most tumors are caused by inherited or acquired genetic changes. However, a subset of tumors is driven by viral infection including Kaposi sarcoma, nasopharyngeal carcinoma, and others. Human papillomavirus (HPV) is an especially common cause of epithelial cancers and hyperplasias. Epidermodysplasia verruciformis (EDV) is a rare type of HPV infection with characteristic histopathologic features and a unique spectrum of HPV subtypes. We report here a distinctive form of EDV-associated eccrine neoplasia. Seven tumors from two patients were analyzed and show highly uniform features including multiple clustered clinical lesions, multifocal epidermal origin, eccrine differentiation with close association with the acrosyringium, an anastomosing growth pattern, and a bland monotonous poroid-to-basaloid cytomorphology. Clinical follow-up for one patient has been benign to date. These tumors show strong similarity to two previously reported cases, suggesting that this type of EDV-associated eccrine neoplasia may represent a rare but reproducible form of skin adnexal tumor with distinctive clinicopathologic features.

Inflammatory and glandular skin disease in pregnancy.

A switch from cell-mediated to humoral immunity (helper T 1 [Th1] to helper T 2 [Th2] shift) during gestation plays a key role in placental immune tolerance. As a result, skin diseases that are Th2 mediated often worsen, whereas skin diseases that are Th1 mediated often improve during gestation. Also, due to fluctuations in glandular activity, skin diseases involving sebaceous and eccrine glands may flare, whereas those involving apocrine glands may improve during pregnancy. Despite these trends, inflammatory and glandular skin diseases do not always follow the predicted pattern, and courses are often diverse. We review the gestational course of inflammatory skin diseases, such as atopic dermatitis (atopic eruption of pregnancy), psoriasis, impetigo herpetiformis, urticaria, erythema annulare centrifugum, pityriasis rosea, sarcoidosis, Sweet syndrome, and erythema nodosum, as well as glandular skin diseases, including acne vulgaris, acne rosacea, perioral dermatitis, hidradenitis suppurativa, Fox-Fordyce disease, hyperhidrosis, and miliaria. For each of these diseases, we discuss the pathogenesis, clinical presentation, and management with special consideration for maternal and fetal safety.

Aminolevulinic Acid Photodynamic Therapy in the Treatment of Erosive Pustular Dermatosis of the Scalp: A Case Series.

IMPORTANCE: Erosive pustular dermatosis of the scalp (EPDS) is an inflammatory skin condition that develops on sun-damaged skin in older individuals. Patients with EPDS present a therapeutic challenge because medical treatments and surgical modalities have met with limited success. Methyl aminolevulinate photodynamic therapy has been effective in 1 case but induced the disease in others. OBSERVATIONS: Eight patients with EPDS with mean (range) age 84 (67-93) years underwent gentle curettage of the hyperkeratotic lesions followed by aminolevulinic acid photodynamic therapy (PDT) 1 to 2 weeks later. Lesions resolved in 6 patients, whereas 2 patients had residual lesions at 6-week follow-up and underwent a second cycle of curettage and aminolevulinic acid PDT with resolution. One patient experienced a partial recurrence 5 months after the procedure and was successfully retreated with curettage + aminolevulinic acid PDT. No adverse effects were noted, and patients were satisfied with the treatment. CONCLUSIONS AND RELEVANCE: This series of patients demonstrated EPDS successfully treated with PDT. Lesions resolved in all patients with a protocol that included curettage followed by aminolevulinic acid PDT. Therefore, this protocol represents an efficacious modality for EPDS.

Dermal eosinophilic infiltrate in junctional epidermolysis bullosa.

Junctional epidermolysis bullosa (JEB) is a rare genodermatosis characterized by a split in the lamina lucida usually because of mutations in LAMA3, LAMB3 and LAMC2 resulting in absence or reduction of laminin-332. Rare subtypes of JEB have mutations in COL17A1, ITGB4, ITGA6 and ITGA3 leading to reduction or dysfunction of collagen XVII, integrin α6ß4 and integrin α3. The classic finding under light microscopy is a paucicellular, subepidermal split. We describe the unusual presence of an eosinophilic infiltrate in the bullae and subjacent dermis in a neonate with JEB, generalized intermediate (formerly known as non-Herlitz-type JEB), discuss the histologic differential diagnosis for a subepidermal blister in a neonate, review the literature regarding cases of epidermolysis bullosa (EB) presenting with inflammatory infiltrates, and discuss mechanisms to explain these findings. This case highlights that eosinophils can rarely be seen in EB and should not mislead the dermatopathologist into diagnosing an autoimmune blistering disorder.

Review of thalidomide use in the pediatric population.

Thalidomide is resurging in the management of adult rheumatologic skin conditions, especially lupus erythematosus. Although use in pediatric patients is reported since the 1990s, there are no systematic reviews describing treatment in children. Thalidomide has immunomodulatory and anti-tumor necrosis factor-α effects as well as antiangiogenic properties, making it useful for a broad spectrum of inflammatory disorders. Thalidomide is second-line treatment for aphthous stomatitis and chronic graft-versus-host disease in children and has been prescribed for many other conditions including actinic prurigo and epidermolysis bullosa pruriginosa. Systemic lupus erythematosus may be less responsive to thalidomide in children than adults. Peripheral neuropathy is observed in both idiosyncratic and dose-dependent relationships; children older than 12 years may be more susceptible to developing this adverse effect than younger patients. There are rare reports of thrombotic complications in children treated for nonmalignant indications. We review the mechanism of action and propose that thalidomide is an alternative treatment for patients who fail or have contraindications to anti-tumor necrosis factor-α biologics.

Neonatal junctional epidermolysis bullosa: treatment conundrums and ethical decision making.

Junctional epidermolysis bullosa (JEB), generalized severe (previously called JEB, Herlitz-type) has an extremely poor prognosis, with a mean age of death at 5 months old and most dead before age 3 years. We describe a typical case of a neonate with JEB who developed failure to thrive before his death from fungal septicemia at 4 months of age. This case highlights the ethical considerations of invasive treatments such as gastrostomy tube placements, intubations, and central line placements in neonates with JEB. We review the literature as well as discuss the ethical conundrums in the care of patients with JEB and other severe forms of epidermolysis bullosa.

Congenital kaposiform hemangioendothelioma with Kasabach-Merritt phenomenon successfully treated with low-dose radiation therapy.

Kaposiform hemangioendothelioma (KHE) associated with Kasabach-Merritt phenomenon is a life-threatening vasculopathy. The current mainstay treatment for KHEs is corticosteroids and chemotherapy, but these medications do not work for all patients and carry significant side effects. We report a neonate with a large congenital KHE who responded extremely well to low-dose radiation therapy.

Surgical approach and outcomes in patients with lithium-associated hyperparathyroidism.

BACKGROUND: Patients receiving lithium therapy are at elevated risk of developing hyperparathyroidism. In lithium-associated hyperparathyroidism (LAH), the incidence of multiglandular disease (MGD) is unclear, and the need for routine bilateral cervical exploration remains controversial. Therefore, in LAH patients, surgical approaches, pathologic findings, cure rates, and factors associated with persistent or recurrent disease were investigated. METHODS: Retrospective analysis of 27 patients with LAH undergoing parathyroidectomy with the intraoperative parathyroid hormone (PTH) assay. RESULTS: The median postoperative follow-up was 7 months; 17 patients had >6 months follow-up. Cervical exploration was unilateral in 9, bilateral in 18 (3 were converted from unilateral). Sixteen patients (62%) had MGD, 12 with four-gland hyperplasia and 4 with double adenomas. Ten patients (38%) had a single adenoma. Twenty-five (93%) of 27 patients had initially successful surgery. Of the 17 patients with >6 months follow-up, two had persistent disease and two experienced recurrent disease. All patients with a single adenoma remain free of disease. Three (75%) of four patients with persistent/recurrent disease had MGD and were receiving lithium at the time of surgery. Patients with persistent/recurrent disease were older (p = 0.01) and had experienced a longer duration of hypercalcemia (p = 0.04). CONCLUSIONS: LAH patients have a high incidence of MGD, and bilateral exploration is frequently necessary. With access to the intraoperative PTH assay, it is reasonable to initiate a unilateral approach because many patients will harbor single adenomas and can be reliably rendered normocalcemic. Patients with MGD remain at higher risk of persistent/recurrent disease.

An incompletely penetrant novel mutation in COL7A1 causes epidermolysis bullosa pruriginosa and dominant dystrophic epidermolysis bullosa phenotypes in an extended kindred.

Epidermolysis bullosa pruriginosa (EBP) is a rare subtype of dystrophic epidermolysis bullosa (DEB) characterized by intense pruritus, nodular or lichenoid lesions, and violaceous linear scarring, most prominently on the extensor extremities. Remarkably, identical mutations in COL7A1, which encodes an anchoring fibril protein present at the dermal-epidermal junction, can cause both DEB and EBP with either autosomal dominant or recessive inheritance. We present one family with both dystrophic and pruriginosa phenotypes of epidermolysis bullosa. The proband is a 19-year-old Caucasian woman who initially presented in childhood with lichenoid papules affecting her extensor limbs and intense pruritus consistent with EBP. Her maternal grandmother saw a dermatologist for similar skin lesions that developed without any known triggers at age 47 and mostly resolved spontaneously after approximately 10 years. The proband's younger brother developed a small crop of pruritic papules on his elbows, dorsal hands, knees, and ankles at age 13. Her second cousin once removed, however, reported a mild blistering disease without pruritus consistent with DEB. Genetic sequencing of the kindred revealed a single dominant novel intron 47 splice site donor G>A mutation, c.4668 + 1 G>A, which we predict leads to exon skipping. Incomplete penetrance is confirmed in her clinically unaffected mother, who carries the same dominant mutation. The wide diversity of clinical phenotypes with one underlying genotype demonstrates that COL7A1 mutations are incompletely penetrant and strongly suggests that other genetic and environmental factors influence clinical presentation.