Tolerability of Narrow-band Ultraviolet-B Phototherapy for Different Dermatological Diseases in Relation to Co-medications.

Phototherapy is an efficient therapy for a variety of skin diseases. Various drugs can cause photosensitivity and impact tolerability of phototherapy. The tolerability was investigated of narrowband ultraviolet-B 311 nm therapy in dependence on the underlying disease and long-term co-medication. A total of 534 narrowband ultraviolet-B therapy courses were examined. Compared with psoriasis, adverse events were observed more frequently in eczematous diseases and, in some cases, other indications. About two-thirds of all courses were carried out in patients taking at least one photosensitising drug, according to the summaries of product characteristics. Phototherapy was more frequently associated with adverse events when medication was taken concomitantly. When considering the tolerability of phototherapy in dependence on individual substances or drug classes, no statistically significant result was shown after adjustment.

Rheumatoid neutrophilic dermatosis under treatment with the interleukin-6-receptor-antagonist sarilumab in a patient with seropositive rheumatoid arthritis.

Skin manifestations may arise as adverse events following the use of novel drugs. We report a case of a patient with seropositive rheumatoid arthritis who developed a rheumatoid neutrophilic dermatosis (RND) under treatment with the interleukin-6-receptor-antagonist sarilumab. The skin lesions developed 2-3 days after the first injection. RND presents with asymptomatic, symmetrical fixed urticarial-like papules, plaques, and nodules, localized typically on the extensor surfaces of the forearms and hands. After discontinuing the medication, the nodules in our patient disappeared within a month.

[DMARD treatment and skin cancer : Recognition, state of knowledge and prevention]. / DMARD-Therapie und Hautkrebs : Erkennen, Stand des Wissens und Prävention.

BACKGROUND AND OBJECTIVE: Epithelial tumors differ in cellular origin, risk factors, incidence, and treatment. This article discusses the extent to which the use of disease-modifying antirheumatic drugs (DMARD) is associated with an increased risk for the development of skin tumors and for which substances the risk may be increased. In addition, some practical dermatological recommendations for rheumatologists are presented. METHODS: The most frequent tumors of the skin are classified according to their cellular origin into malignant melanoma (MM) and so-called keratinocyte cancer (KC). The clinical presentation of these tumors differs and also the risk for the development of these epithelial skin tumors under DMARD treatment varies depending on the drug and tumor entity. As rheumatologists frequently see these patients for follow-up, it is essential to know the clinical findings as well as the corresponding risk factors of the specific tumor entities. RESULTS: A generally valid and reliable estimation of the risk for the development of epithelial skin tumors under DMARD treatment can only be formulated in the form of tendencies at the present time due to the lack of data. The relevant literature shows that regular intensive dermatological screening is recommended. CONCLUSION: Patients undergoing immunosuppressive or immune-modulating treatment should be instructed in self-inspection of the skin, receive regular dermatological check-ups and be instructed in strict UV protection methods. Lesions that do not heal or recurrently bleed should be referred for a punch biopsy to rule out or diagnose an epithelial skin tumor, as should atypical inflammatory lesions that do not heal with the use of topical glucocorticoids. An interdisciplinary approach in patient management is the key to success in ensuring the maximum quality of life with the lowest possible risk of developing epithelial skin tumors for these patients.

Early Exanthema Upon Vemurafenib Plus Cobimetinib Is Associated With a Favorable Treatment Outcome in Metastatic Melanoma: A Retrospective Multicenter DeCOG Study.

BACKGROUND: The combination of BRAF and MEK inhibitors has become standard of care in the treatment of metastatic BRAF V600-mutated melanoma. Clinical factors for an early prediction of tumor response are rare. The present study investigated the association between the development of an early exanthema induced by vemurafenib or vemurafenib plus cobimetinib and therapy outcome. METHODS: This multicenter retrospective study included patients with BRAF V600-mutated irresectable AJCC-v8 stage IIIC/D to IV metastatic melanoma who received treatment with vemurafenib (VEM) or vemurafenib plus cobimetinib (COBIVEM). The development of an early exanthema within six weeks after therapy start and its grading according to CTCAEv4.0 criteria was correlated to therapy outcome in terms of best overall response, progression-free (PFS), and overall survival (OS). RESULTS: A total of 422 patients from 16 centers were included (VEM, n=299; COBIVEM, n=123). 20.4% of VEM and 43.1% of COBIVEM patients developed an early exanthema. In the VEM cohort, objective responders (CR/PR) more frequently presented with an early exanthema than non-responders (SD/PD); 59.0% versus 38.7%; p=0.0027. However, median PFS and OS did not differ between VEM patients with or without an early exanthema (PFS, 6.9 versus 6.0 months, p=0.65; OS, 11.0 versus 12.4 months, p=0.69). In the COBIVEM cohort, 66.0% of objective responders had an early exanthema compared to 54.3% of non-responders (p=0.031). Median survival times were significantly longer for patients who developed an early exanthema compared to patients who did not (PFS, 9.7 versus 5.6 months, p=0.013; OS, not reached versus 11.6 months, p=0.0061). COBIVEM patients with a mild early exanthema (CTCAEv4.0 grade 1-2) had a superior survival outcome as compared to COBIVEM patients with a severe (CTCAEv4.0 grade 3-4) or non early exanthema, respectively (p=0.047). This might be caused by the fact that 23.6% of patients with severe exanthema underwent a dose reduction or discontinuation of COBIVEM compared to only 8.9% of patients with mild exanthema. CONCLUSIONS: The development of an early exanthema within 6 weeks after treatment start indicates a favorable therapy outcome upon vemurafenib plus cobimetinib. Patients presenting with an early exanthema should therefore be treated with adequate supportive measures to provide that patients can stay on treatment.

Varying Mutational Alterations in Multiple Primary Melanomas.

In melanoma, the mitogen-activated protein (MAP) kinase pathway plays a crucial oncogenic role. Recent studies identified additional genetic alterations, eg, TERT-promoter mutations. Up to 8% of melanoma patients present with multiple primary melanomas (MPMs). The pathogenesis is not fully understood, and data on the genetic diversity of MPMs are limited. To identify putative diagnostic and therapeutic consequences, we assessed the mutational status of the BRAF and NRAS genes and TERT promoter in patients with MPMs. The study cohort consisted of 96 patients with 237 malignant melanomas. The BRAF, NRAS, and TERT-promoter genotypes were assessed in all MPMs and were correlated with patients' clinicopathological characteristics. BRAF mutations were found in 84 melanomas (35.4%), NRAS mutations, in 33 (14.0%); and TERT-promoter mutations, in 112 (47.3%). Mutation patterns were concordant between first and subsequent primary tumors in 23.9% of patients and were discordant in 61.4% of patients. The genetic alterations were partially different in 14.7% of patients. By Cox regression analysis, only the NRAS mutation had a significant negative prognostic impact on time to progression to stage III (P = 0.016) and on distant metastasis-free survival (P = 0.032). In the majority of primary melanomas in patients with MPMs, BRAF, NRAS, and TERT-promoter genotypes were discordant. Thus, molecular testing for targeted therapy should be performed on metastatic tissue and not on primary tumors.