Dermatological adverse events under programmed cell death-1 inhibitors as a prognostic marker in metastatic melanoma.

Melanoma is widely treated with programmed cell death-1 (PD-1) inhibitors. As part of their anti-tumor immunity effect, they increase the susceptibility to cutaneous immune-related adverse events (cIRAE) among other autoimmune effects. To characterize the manifestations of cIRAE in melanoma patients treated with PD-1 inhibitors, and evaluate the correlation with tumor response. A retrospective study of 95 metastatic malignant melanoma patients treated with PD-1 inhibitors at the Hadassah Medical Center during 2013-2016. The most common cIRAE was pruritus reported by 39 (41%) patients. All other cIRAE were noted in 34 patients (35.8%), of which the most common cutaneous manifestation was vitiligo, demonstrated in 17 patients (17.9%) followed by various rashes (7.4%, including erythema multiforme, oral lichen planus, photosensitive rash, insect bite-like reaction, and urticaria), psoriasiform rash (3.2%), bullous pemphigoid (3.2%), and eczema (1%). Interestingly, higher response rates to immunotherapy were demonstrated in patients who developed pruritus (85%) and cIRAE (88%), with lower mortality rates in the cIRAE group (38.2%) versus the non-cIRAE group (70.5%, p = 0.002). cIRAE are common among malignant melanoma patients treated with PD-1 inhibitors and may be a marker for favorable prognosis.

Necrotizing sialometaplasia related to vomiting and silastic ring vertical gastroplasty.

Necrotizing sialometaplasia (NS) is a self-limiting, ulcerated, benign process, affecting minor salivary glands most commonly in the palate. The comorbidity of eating disorders with NS is rare. We present a patient with bilateral NS who suffered from frequent episodes of vomiting. Review of the literature revealed a handful of such cases. The possible role of vomiting in the pathogenesis of NS is argued.

Prevalence of interdigital psoriasis of the feet ("psoriasis alba") in mild, moderate, and severe psoriasis.

Interdigital psoriasis of the feet ("psoriasis alba") is a rare form of inverse psoriasis. We conducted a cross-sectional study of the prevalence of interdigital psoriasis in mild, moderate, and severe psoriasis, compared to atopic dermatitis and normal controls. Data were collected during 2010-2013 from 232 psoriatic patients, 190 patients with atopic dermatitis, and 202 normal controls. The psoriatic and atopic dermatitis patients were from the dermatology department and outpatient clinic of the Hadassah-Hebrew University Medical Center in Jerusalem, Israel. The normal controls were healthy workers and volunteers from Hadassah Hospital who were not aware of any dermatological disease and had never consulted a general practitioner or dermatologist for skin problems of the feet. Our study revealed a prevalence of 2.6% of interdigital psoriasis of the feet in psoriatic patients, especially in men, and none in atopic dermatitis and normal controls. Three of the six affected patients with interdigital psoriasis of the feet complained of itching, both feet were involved in four patients, while two presented with additional palmoplantar psoriasis. The hematoxylin and eosin histopathological findings were in line with those found in inverse psoriasis. Dermatologists should be aware of this entity and treat it correctly. The diagnosis should be considered in psoriatic patients presenting with whitish plaque or patches in the toe-webs, in whom the fungal test is negative and are not responding to antimycotic treatment.

Oral syphilis lesions--a diagnostic approach and histologic characteristics of secondary stage.

Syphilis is among the oldest recognized sexually transmitted diseases. In the past decade, its incidence has risen significantly in the developed world. Oral syphilitic lesions, the most common extragenital sign of infection, are a diagnostic challenge to dentists, who are usually the first to examine the oral lesions. Biopsies are occasionally the first examination performed, but histologic findings are considered nonspecific. We present two new cases as well as an additional 25 published cases, suggesting that plasma cell arteritis and plasma cell neuritis is a combination that has not been reported in any other pathologic condition of the oral cavity and may be specific enough to direct the clinician toward a diagnosis of syphilis prior to clinical confirmation.

Chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature syndrome: a case report.

Chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature syndrome is a recently described chronic inflammatory syndrome consisting of widespread annular violaceous skin lesions and multisystemic inflammatory manifestations. We report a 12½-year-old boy with a young-age onset of recurrent fevers, annular violaceous plaques, alopecia areata, lipodystrophy, low weight and height, deformed fingers, wide-spaced nipples, chronic anemia, and elevated acute phase reactants. An abdominal punch biopsy demonstrated dense perivascular and interstitial infiltrates in the dermis, composed mainly of mononuclear cells. This syndrome may represent a new autosomal recessive auto-inflammatory genodermatosis. Increased awareness may lead to the discovery of more cases, and clarify its pathogenesis.

Atypical "allergic crease".

BACKGROUND: The allergic crease (nasal crease) is a transverse line, common among patients who suffer from allergic rhinitis. Although it is a very prevalent condition, the skin manifestations which accompany this condition have been only sparsely reported. MAIN OBSERVATION: We describe an 18-year-old man with allergic rhinitis, who developed cornified papules along an allergic crease. Dermoscopic examination revealed oval, slightly raised, gray, sharply demarcated papules. Histopathology revealed seborrheic keratosis like hyperplasia, accompanied by horn cysts. CONCLUSIONS: To our knowledge, cornified papules have not been reported previously along the allergic crease. Considering the fact that allergic rhinitis is a common chronic condition of childhood, increased awareness of the skin manifestations which accompany this condition is essential.

Inflammatory and chloracne-like skin lesions in B6C3F1 mice exposed to 3,3',4,4'-tetrachloroazobenzene for 2 years.

Exposure to dioxin and dioxin-like compounds (DLCs) has been connected to the induction of chloracne in humans and animals. 3,3',4,4'-Tetrachloroazobenzene (TCAB) is an environmental contaminant that induces chloracne in humans. TCAB has been studied only to a limited extent in laboratory animals. While performing a 2-year gavage study in B6C3F1 mice to evaluate the toxic and carcinogenic effects of TCAB, we also explored potential chloracnegenic properties. Groups of 50 male and 50 female B6C3F1 mice were exposed by gavage to TCAB at dose levels of 0, 3, 10 and 30 mg/kg for 5 days a week for 2 years. The animals developed treatment-related gross inflammatory skin lesions, which were characterized histologically by inflammation, fibrosis, hyperplasia, and ulcers. Additionally, many of the animals developed follicular dilatation and sebaceous gland atrophy, consistent with chloracne-like lesions. This current 2-year study supports recently published papers showing susceptibility to chloracne in mouse strains other than hairless mice. The chloracne-like lesions were not clinically evident; therefore, our study highlights the need for careful examination of the skin in order to identify subtle lesions consistent with chloracne-like changes in rodents exposed to dioxin and DLCs. Since previous short-term studies did not demonstrate any skin lesions, we suggest that reliable assessment of all safety issues involving dioxin and DLCs requires evaluation following chronic exposure. Such studies in animal models will help to elucidate the mechanisms of dioxin-related health hazards.

Fluorescence imaging for the demarcation of basal cell carcinoma tumor borders.

BACKGROUND: Basal cell carcinoma (BCC) is a common malignancy accounting for 80% of all nonmelanoma skin cancers. Mohs micrographic surgery (MMS) is considered superior to alternative treatments, but the procedure is time consuming and costly. Alternative simpler techniques to facilitate accurate tumor demarcation are therefore in demand. Fluorescence imaging following application of 5-aminolevulinic acid is a noninvasive diagnostic technique that gives rapid information about the superficial extent of the skin tumor. OBJECTIVE: To ascertain whether fluorescence imaging improves the clinical tumor border assessment by investigating the consistency between tumor size determination by MMS, clinical assessment, and fluorescence imaging. METHODS: Eighteen patients with histologically verified nodular BCCs on the face scheduled for MMS were included in the study. The night before the surgical procedure, 5-aminolevulinic methyl ester cream was applied to the lesion. The following morning, tumor borders were determined clinically (clinical size), after illumination with Wood's light (fluorescence size), and by the tumor defect left on the skin surface following removal of the MMS specimen (Mohs size). RESULTS: The median tumor sizes were 93.05 mm2 (Mohs size), 61.05 mm2 (clinical size), and 72.75 mm2 (fluorescence size). The interclass correlation coefficients between Mohs size and fluorescence size was 0.984 and Mohs size and clinical size was 0.752. CONCLUSION: Tumor border estimation by fluorescence imaging and clinical assessment underestimate the genuine tumor size determined by MMS; however, the fluorescence size showed a higher degree of consistency with the Mohs size than did the clinical size.

Involvement of the CXCL12/CXCR4 pathway in the recovery of skin following burns.

Burn wound healing is a complex process consisting of an inflammatory phase, the formation of granulation tissue, and remodeling. The role of the CXCL12/CXCR4 pathway in the recovery of skin following burns is unknown. We found that CXCL12 is similarly expressed in human, swine, and rat skin by pericyte and endothelial cells, fibrous sheet, fibroblasts, and axons. Following burns, the levels of CXCL12 were markedly increased in human burn blister fluids. One day after injury, there was a gradual increase in the expression of CXCL12 in the hair follicles and in blood vessel endothelium surrounding the burn. Three to 11 days following burns, an increased number of fibroblasts expressing CXCL12 were observed in the recovering dermis of rat, swine, and human skin. In contrast to CXCL12, CXCR4 expression was detected in proliferating epithelial cells as well as in eosinophils and mononuclear cells infiltrating the skin. In vitro, CXCL12 was expressed by primary human skin fibroblasts, but not by keratinocytes, and was stimulated by wounding a confluent cell layer of these fibroblasts. Blocking the CXCR4/CXCL12 axis resulted in the significant reduction in eosinophil accumulation in the dermis and improved epithelialization. Thus, blocking CXCR4/CXCL12 interaction may significantly improve skin recovery after burns.