How I explore...a disorder with an apparently healthy microscopic aspect of the skin.

peer reviewedSome dermatologic disorders named "Invisible dermatoses" are defined by obvious clinical signs while histologic alterations remain discrete. This situation may lead to clinico-pathological discrepancies impeding the establishment of a diagnosis. In other cases, the skin looks clinically normal but the histological examination allows to disclose some systemic diseases. Systematic analysis of the skin biopsy complemented by histochemical and immunohistochemical techniques may help reach the diagnosis

Identifying the potential origin of mucin in primary cutaneous mucinoses: A retrospective study and analysis using histopathology and multiplex fluorescence staining

Background: Primary cutaneous mucinoses (PCM) are rare diseases characterized by dermal or follicular mucin deposits. Objectives: A retrospective study characterizing PCM to compare dermal with follicular mucin to identify its potential origin on a single-cell level. Material and methods: Patients diagnosed with PCM between 2010 and 2020 at our department were included in this study. Biopsy specimens were stained using conventional mucin stains (Alcian blue, PAS) and MUC1 immunohistochemical staining. Multiplex fluorescence staining (MFS) was used to investigate which cells were associated with MUC1 expression in select cases. Results: Thirty-one patients with PCM were included, 14 with follicular mucinosis (FM), 8 with reticular erythematous mucinosis, 2 with scleredema, 6 with pretibial myxedema and one patient with lichen myxedematosus. In all 31 specimens, mucin stained positive for Alcian blue and negative for PAS. In FM, mucin deposition was exclusively found in hair follicles and sebaceous glands. None of the other entities showed mucin deposits in follicular epithelial structures. Using MFS, all cases showed CD4+ and CD8+ T cells, tissue histiocytes, fibroblasts and pan-cytokeratin+ cells. These cells expressed MUC1 at different intensities. MUC1 expression in tissue histiocytes, fibroblasts, CD4+ and CD8+ T cells, and follicular epithelial cells of FM was significantly higher than the same cell types in the dermal mucinoses (p < 0.001). CD8+ T cells were significantly more involved in expression of MUC1 than all other analysed cell types in FM. This finding was also significant in comparison with dermal mucinoses. Conclusion: Various cell types seem to contribute to mucin production in PCM. Using MFS, we showed that CD8+ T cells seem to be more involved in the production of mucin in FM than in dermal mucinoses, which could indicate that mucin in dermal and follicular epithelial mucinoses have different origins

Modulator Therapy for Cystic Fibrosis: An Exploration of Current Research

Developing a drug therapy that addresses the root cause of cystic fibrosis (CF) by increasing CFTR protein levels has long been a research challenge. After genetic therapy failed because a suitable delivery system could not be found, researchers began searching for small organic molecules that could act as chaperones for CFTR. These molecules, known as modulators, allowed CFTR to be assembled correctly and function similarly to wild type CFTR. Since 2012, four modulator drugs have been developed, tested, and approved by the FDA. In October 2019, Trikafta was approved as the first triple-combination modulator drug and has completely revolutionized CF therapy. This paper details the research challenges, successes, and failures that led to the development of modulator therapies

Discrete papular lichen myxedematosus: a rare entity or an under- diagnosed disease?

Primary cutaneous mucinoses are characterized by abnormal mucin deposits in the skin. Discrete papular lichenmyxedematosus (DPLM) is an unusual subtype which is characterized by the presence of multiples  smooth, waxy, or flesh-colored papules, 2 to 5 mm in size affecting the trunk and limbs and most commonly proximal sites. We report a 42-year-old man with both the clinical and histopathological described criteriaKey words: Mucinosis-discrete, papular lichen, myxedematosu

Plaque-Like Sclerodermiform Localized Mucinosis Rapidly Responsive to Topical Tacrolimus

We report the successful treatment of plaque-like sclerodermiform mucinosis using tacrolimus ointment topically. We present a 70-year-old male with a large chronic erythema and hardening of the nuchal skin and shoulder area. Subjective symptoms were a moderate pruritus and a rather disabling stiffness. A biopsy specimen revealed typical features of lichen myxedematosus. In a subsequent clinical examination, no associated illnesses such as hypothyroidism or gammopathy were found. Since no established therapy exists for this condition, and as there was a lack of response to potent topical glucocorticosteroids, tacrolimus 0.03% ointment was used off-label twice daily. Surprisingly, this resulted in a rapid, almost complete clearance of the skin within three weeks of treatment

Reticular erythematous mucinosis: A rare cutaneous mucinosis

Reticular erythematous mucinosis (REM) is a rare form of primary cutaneous mucinosis, most often involving the midline of the upper chest or back in middle-aged women. REM bears clinical and histopathologic resemblance to lupus erythematosus tumidus (LET), dermatomyositis, scleredema, and lichen myxedematosus. Early recognition and diagnosis of REM is particularly relevant to exclude the abovementioned diseases, as REM is more benign and has fewer systemic consequences. </p

Discrete Papular Lichen Myxedematosus and Scleromyxedema with Hypothyroidism: A Report of Two Cases

Scleromyxedema and lichen myxedematosus (LM) are rare disorders that fall along the spectrum of primary cutaneous mucinoses. Scleromyxedema is a systemic form that classically presents with generalized waxy papules, sclerodermoid eruption, and monoclonal gammopathy; LM is a localized form limited to the skin that classically presents with white, firm, waxy papules and lacks monoclonal gammopathy. According to diagnostic criteria established in 2001, the diagnosis of both conditions requires absence of thyroid disease. However, atypical cases that lack monoclonal gammopathy and that present with hypothyroidism have been reported, suggesting that these criteria may require revision. First, we report a case of a 58-year-old female with a history of Hashimoto thyroiditis and biopsy-proven scleromyxedema responsive to intravenous immunoglobulin therapy with delayed presentation of monoclonal gammopathy. Next, we report a case of a 54-year-old female with a history of hypothyroidism, Hodgkin’s lymphoma in remission after radiation and chemotherapy, and concurrent rheumatoid arthritis, with biopsy-proven LM temporarily responsive to systemic steroids. Our cases demonstrate that patients with papular mucinoses can have a multitude of concurrent and prior rheumatologic and endocrine conditions, including thyroid disease, which should not preclude a diagnosis of scleromyxedema and LM

Dermatoses com Alterações Histológicas Mínimas: Tornar o Invisível Visível

Skin biopsies remain an indispensable tool for aiding dermatologists in accurate diagnosis and treatment. However, some clinically evident skin diseases show histological picture resembling normal skin when examined after preparation with hematoxylin and eosin (H&amp;E). In order to establish the correct diagnosis, clinicopathological correlation is essential, together with further investigations such as special stains and immunohistochemistry techniques. Hereby, we discuss the most relevant of these “invisible” dermatoses on H&amp;E, and include strategy for approaching such cases.As biópsias cutâneas continuam a ser uma ferramenta indispensável no auxílio de dermatologistas para um diagnóstico e tratamento precisos. Contudo, algumas doenças dermatológicas clinicamente evidentes mostram imagens histológicas normais, quando examinadas após preparação com hematoxilina-eosina (H&amp;E). No sentido de estabelecer um diagnóstico correcto, é essencial a correlação clínico-patológica ou executar outras investigações adicionais, como colorações especiais e técnicas de imuno-histoquímica. Neste artigo, são discutidas as mais relevantes destas dermatoses “invisíveis” em H&amp;E, incluindo a estratégia de abordagem nestes casos