A Systematic Review of Clinical Studies on Mucocutaneous Manifestations of COVID-19: Virus-Related and Drug-Related

Coronavirus could affect almost any part of the body including the skin. In this systematic review, the primary skin lesions resulting from the direct activity of the virus or the medications used for treatment and the changes in the behavior of the virus regarding the occurrence of these symptoms over time were assessed. PubMed/MEDLINE, Embase, PsycINFO, TRIP Cochrane, Cochrane Skin were searched for all published articles from February 19 to July 1, 2020, which met the inclusion criteria. Thirty-six related articles were extracted. Twenty-eight studies reported virus-related mucocutaneous eruptions and 8 articles, the drug-reactions. Data of 583 patients were included. Skin lesions of COVID-19 could be caused by both the virus itself or the influence of drugs used for the treatment. Morbilliform rashes, urticaria, and acral-vasculopathic cutaneous lesions were at the forefront of primary COVID-dependent skin lesions with no significant change during time, Also, Hydroxychloroquine, lopinavir/ritonavir, paracetamol, and antibiotics were reported as the main causes of drug-induced rashes. Since dermatologic manifestations may occur prior or simultaneously/after other COVID clinical symptoms, so they may helpful in patients’ early diagnosis or prediction of internal organ involvements via histopathologic evaluations of skin biopsies especially about vasculopathic and vasculitic, respectively.

Intractable pruritus in chronic myelomonocytic leukaemia and myelodysplastic syndromes: a case series

Intractable pruritus without visible primary skin lesions and refractory to antihistamines as a primary presentation of chronic myelomonocytic leukaemia (CMML) and myelodysplastic syndrome (MDS) is not well recognised. We present two cases of CMML and two cases of MDS with this challenging symptom. In two of them, the pruritus preceded the diagnosis of MDS/CMML by months. Various chemotherapeutic and immunosuppressive options were used with variable success. In one of the cases, the pruritus persisted despite achieving morphological remission of CMML with azacitidine but had a remarkable complete response to cladribine. The pathogenesis of intractable itching in CMML and MDS remains unclear but seems to be linked to the biology of these diseases and could precede definitive diagnostic features. Earlier diagnosis of these myeloid disorders may therefore be aided by increasing awareness among clinicians of the association with pruritus.

Epigenetic dysregulation underpins tumorigenesis in a cutaneous tumor syndrome

Patients with CYLD cutaneous syndrome (CCS; syn. Brooke-Spiegler syndrome) carry germline mutations in the tumor suppressor CYLD and develop multiple skin tumors with diverse histophenotypes 1,2. We comprehensively profiled the genomic landscape of 42 benign and malignant tumors across 13 individuals from four multigenerational families. Novel driver mutations were found in epigenetic modifiers DNMT3A and BCOR in 29% of benign tumors. Multi-level and microdissected sampling strikingly reveal that many clones with different DNMT3A mutations exist in these benign tumors, suggesting that intra-tumor heterogeneity is common. Integrated genomic and methylation profiling suggest that mutated DNMT3A drives tumorigenesis mechanistically through Wnt/ß-catenin pathway signaling. Phylogenetic and mutational signature analyses confirm the phenomenon of benign pulmonary metastases from primary skin lesions. In malignant tumors, additional epigenetic modifiers MBD4, CREBBP, KDM6A and EP300 were mutated. We thus present epigenetic dysregulation as a driver in CCS tumorigenesis and propose this may account for the diverse histophenotypic patterns despite the paucity of mutations seen. These findings add novel dimensions to existing paradigms of cutaneous tumorigenesis and metastasis.