Efficacy and safety of crisaborole ointment, 2%, in participants aged ≥45 years with stasis dermatitis: Results from a fully decentralized, randomized, proof-of-concept phase 2a study.

BACKGROUND: Crisaborole ointment, 2%, is a nonsteroidal topical phosphodiesterase 4 inhibitor approved for the treatment of mild-to-moderate atopic dermatitis. OBJECTIVE: To evaluate the efficacy and safety of crisaborole in stasis dermatitis (SD). METHODS: In this randomized, double-blind, vehicle-controlled, decentralized phase 2a study (NCT04091087), 65 participants aged ≥45 years with SD without active ulceration received crisaborole or vehicle (1:1) twice-daily for 6 weeks. The primary end point was percentage change from baseline in total sign score at week 6 based on in-person assessment. RESULTS: Crisaborole-treated participants had significantly reduced total sign score from baseline versus vehicle based on in-person (nondermatologist) assessment (-32.4% vs -18.1%, P = .0299) and central reader (dermatologists) assessment of photographs (-52.5% vs -10.3%, P = .0004). Efficacy according to success and improvement per Investigator's Global Assessment score and lesional percentage body surface area reached statistical significance based on central reader but not in-person assessments. Skin and subcutaneous tissue disorders were common all-causality treatment-emergent adverse events with crisaborole. LIMITATIONS: Small sample size and short treatment duration were key limitations. In-person assessment was not conducted by dermatologists. CONCLUSION: Crisaborole improved signs and symptoms of SD and was well tolerated. Central reader assessment represents a promising approach for siteless clinical research.

[Pretibial myxedema after Graves' disease: A differential diagnosis of lymphedema]. / Myxœdème prétibial pseudo-tumoral après une maladie de Basedow : un diagnostic différentiel du lymphœdème.

INTRODUCTION: Pretibial myxedema is a rare manifestation of Graves' disease, and pseudotumoral forms may be confused with lower limb lymphedema. OBSERVATIONS: We reported 3 cases of pretibial myxedema in 2 women and 1 man, aged 72, 66, and 49 years, treated for Graves' disease 3, 25 and 32 years previously. Two patients were active smokers. Lymphedema diagnosis of the lower limbs was suspected in the presence of bilateral pseudotumoral lesions of the feet, toes and ankles and the presence of a Stemmer's sign (skin thickening at the base of the 2nd toe, pathognomonic of lymphedema). Lymphoscintigraphy in one case was normal, not confirming lymphedema. CONCLUSION: Pretibial pseudotumoral myxedema is a differential diagnosis of lower limb lymphedema. This diagnosis is confirmed by questioning the patient about preexisting Graves' disease, the underlying etiology, to decide the appropriate treatment and to encourage cessation of smoking, which is a risk factor for pretibial myxedema.

Novel teprotumumab treatment of severe thyroid dermopathy; ototoxicity as an adverse side effect.

Pretibial myxedema, more generally thyroid dermopathy, results from mucopolysaccharide accumulation in the dermis, typically between the knee and dorsal foot. Thyroid dermopathy presents in Graves disease, but can occur in Hashimoto thyroiditis, primary hypothyroidism, and euthyroid patients. Treatment of thyroid eye disease with teprotumumab is established in the literature, with few case reports also showing improvement in pretibial myxedema. Reported is a 76-year-old man with thyroid eye disease and pretibial myxedema treated with teprotumumab; improvement was demonstrated in both conditions. He developed "muffled" hearing as an adverse effect, a complication not widely published in the dermatology literature. At 18 months post-treatment, his symptoms are stable without recurrence, but hypoacusis persists. Given the long-term efficacy and side-effects, dermatologists should recognize the potential benefits and risks of using teprotumumab for thyroid dermopathy. A baseline audiogram may be considered prior to therapy. Additionally, longitudinal data is needed to document the benefits and risks of this novel therapy.

Stasis Dermatitis: An Overview of Its Clinical Presentation, Pathogenesis, and Management.

Stasis dermatitis is a chronic inflammatory skin disease of the lower extremities. It typically occurs in older individuals and is the cutaneous manifestation of venous hypertension caused by venous reflux. Such retrograde venous blood flow is the result of incompetent venous valves, valve destruction, or venous obstruction. Stasis dermatitis is eczematous. The associated impairment of venous valves may cause swelling of the legs, leading to serious conditions including venous ulcerations. Diagnosis can be challenging because of its clinical resemblance to other skin conditions and poor clinical recognition by physicians. The cornerstones of stasis dermatitis treatment are compression therapy to ameliorate pain and swelling, topical treatments to alleviate secondary skin changes, and interventional treatment options to correct the underlying causes of venous reflux. Given the central role of inflammation of the lower extremities in driving the cutaneous changes characteristic of stasis dermatitis, new therapeutic approaches that target the inflammation are under clinical evaluation in patients with stasis dermatitis.

Stasis dermatitis is a skin disease that can affect a person for a long time. It affects the legs of older people who have a disease called chronic venous insufficiency. This is when a person's veins have difficulty sending blood from their limbs back to their heart. Stasis dermatitis is caused by increased pressure inside a person's veins. Its signs and symptoms are skin discoloration, itch, dryness, and scaling and can be similar to the signs and symptoms of cellulitis and allergic contact dermatitis. Cellulitis is a common skin infection caused by bacteria. Cellulitis causes redness, swelling, and pain. Allergic contact dermatitis is an itchy skin rash caused by contact with something that irritates the skin. Stasis dermatitis is usually diagnosed after a healthcare provider has looked at person's skin and their medical history. Treatment for stasis dermatitis should treat the chronic venous insufficiency that causes the disease. It should also treat the skin lesions caused by stasis dermatitis. One way to treat stasis dermatitis is to reduce pain and swelling. This is done by applying pressure with compression stockings or bandages. Minor surgery can treat the venous insufficiency that causes stasis dermatitis. No treatments have been approved for the skin symptoms associated with stasis dermatitis. New ways to treat such symptoms need to be developed.

Hemangioendotelioma epitelioide cutáneo extenso multifocal agresivo. Informe de un caso / Aggressive multifocal extensive cutaneous epithelioid haemagioendothelioma. A case report

El hemangioendotelioma epitelioide es un tumor vascular infrecuente, descrito por primera vez en 1975 por Dail y Liebow como un carcinoma bronquioloalveolar. Habitualmente, se comporta como una neoplasia de bajo grado; sin embargo, se han descrito casos en los que el tumor manifiesta una elevada agresividad, extendiéndose con rapidez por todo el organismo. Presentamos el caso de un hombre de 41 años con dermatosis en muslo izquierdo y extensión rápida a abdomen, cuyo diagnóstico inicial fue de un carcinoma metastásico vs. linfoma. En la revisión de laminillas, se confirmó el diagnóstico de hemangioendotelioma epitelioide de piel, iniciando tratamiento con radioterapia. Este tumor afecta excepcionalmente la piel, habiéndose descrito pocos casos en la literatura médica.(AU)

Epithelioid haemangioendothelioma is a rare vascular tumor, first described in 1975 by Dail and Liebow as a bronchioloalveolar carcinoma. Although it usually behaves like a low-grade neoplasm, cases have been reported in which the tumor shows a high grade of malignancy, spreading rapidly throughout the body. We present the case of a 41-year-old man with dermatosis in the left thigh with rapid extension to the abdomen; the initial differential diagnoses were metastatic carcinoma versus lymphoma. When the histopathology was re-examined, a diagnosis of skin epithelioid hemangioendothelioma was confirmed and treatment with radiotherapy was initiated. This tumour rarely affects the skin; there are only a few previously reported cases.(AU)

Differentiation of hydrochlorothiazide-induced dermatitis from stasis dermatitis.

A woman in her 60s with a history of hypertension and stasis dermatitis presented to a primary care clinic with a bilateral, erythematous rash on the legs, stomach, and chest. Photosensitive rash and dermatitis may be caused by many conditions. Hydrochlorothiazide-induced dermatitis is a rare side effect of thiazide diuretics. Early identification of sulfa-sensitivity and photoallergic or phototoxic reaction is essential to accurate diagnosis and treatment of photosensitive dermatitis. Soliciting a targeted history is essential to delineating drug-induced dermatitis from stasis dermatitis. A thorough skin examination can elucidate the focal or extensive nature of the rash and is essential to making an accurate diagnosis. Immediate cessation of hydrochlorothiazide and switching drugs classes for hypertension management typically leads to resolution of symptoms.

Atypical ulcer arising on stasis dermatitis: achromic melanoma.

INTRODUCTION: Due to venous insufficiency, a vascular ulcer frequently occurs with the progression of stasis dermatitis. Achromic melanoma, a rare form of pigmentless melanoma frequently located on the sole of the foot, is often and easily confused with a typical wound. Diagnosis of ulcerated achromic melanoma is thus often delayed and associated with a poor prognosis. CASE REPORT: The authors report a very rare case of malignant melanoma in a 70-year-old female with stasis dermatitis. The painless ulcer was present for 1 year before the first visit. Upon clinical examination, a 2-cm diameter hypergranulating ulcer with irregular and pigmented borders was present. Dermoscopy revealed the presence of red globules, a gray-to-blue veil, irregular vessels, and the remains of a pigmented ridge pattern. Histological analysis showed infiltration of atypical melanocytes in the dermis, 2 mitoses, and ulceration. Diagnosis of melanoma was confirmed by positive MART-1 immunochemistry. After removal of the melanoma, the area was covered with an autologous skin graft excised from the inner thigh. In accordance with the guidelines, sentinel lymph node biopsy was performed, and the result was negative for lymph node involvement. A comprehensive clinical dermoscopic evaluation led to the correct diagnosis. CONCLUSIONS: The current case highlights the importance of evaluating a chronic, atypical, nonhealing ulcer clinically and dermoscopically as well as through a biopsy procedure.

Obesity-associated lymphedematous mucinosis and stasis mucinosis.

Cutaneous dermal mucinoses are a group of conditions characterized by abnormal deposition of mucin (hyaluronic acid and sulfated glycosaminoglycans) in the dermis. They can be classified either as localized or generalized forms and occur primarily or secondarily to systemic disorders. Obesity-associated lymphedematous mucinosis and pretibial stasis mucinosis are uncommon and relatively newly recognized disorders occurring in obese patients or in patients with venous insufficiency. Clinically, patients present with papules and nodules progressing to plaques and arising in an erythematous and edematous basis on the legs, especially the shins. Histopathologic examination indicates mucin deposition in the superficial portion of the dermis, angioplasia with an increase in small blood and/or lymphatic vessels, vertically running vessels, slight fibrosis, and no inflammation. Laboratory workup and histopathologic testing are helpful in differentiating these entities from pretibial myxedema (thyroid dermopathy), which represents the main differential diagnosis. Obesity-associated lymphedematous mucinosis and stasis mucinosis are not different entities but belong to a spectrum of mucinoses secondary to an increased body mass index, chronic lymphedema, and/or chronic venous insufficiency.

Local immune microenvironment of skin may play an important role in the development of pretibial myxedema.

Pretibial myxedema (PTM), characterized by the accumulation of glycosaminoglycans in dermis is an autoimmune skin disorder, which is almost always associated with Graves' disease (GD). Although fibroblast stimulated by thyroid-stimulating hormone receptor (TSHR) antibody, cytokines and growth factors have been postulated as target of the autoimmune process in the dermopathy, the pathogenesis of PTM remains unclear. We hypothesize that the local immune microenvironment of the skin including the antigens and antibodies, T cells, B cells, plasma cells and fibroblasts may play an important role in the development of PTM. Results obtained on PTM patients indicate increased thyroid-stimulating hormone receptor antibodies (TRAb) in the blood positively correlate with the dermal thickness of the lesions. Further analysis shows that there were more CD3+ T cells and CD20+ B cells in the skin lesions. These T and B cells are in close contact, indicating that inducible skin-associated lymphoid tissue (iSALT) may be formed in the area. In addition, we found that the infiltrating plasma cells can secrete TRAb, proving that B cells in the skin other than the thyroid are an additional source of TSHR antibodies. Meanwhile, the T and B cells in the skin or skin homogenate of patients can promote the proliferation of pretibial fibroblasts. In conclusion, our results provide evidence that the local immune microenvironment of the skin may play an important role in the development of PTM.

The chameleon rash: a review of the polyphenotypic dermatoses of dermatomyositis.

Dermatomyositis (DM) is an autoimmune connective tissue disease that is included in the idiopathic inflammatory myopathies. Cutaneous manifestations are a prominent part of the condition: some skin signs in DM are common to most patients, while other signs are encountered infrequently. A number of features are pathognomic for DM. The demonstration of myositis-specific antibodies (MSAs) in DM has extended the ability to define phenotypic subgroups. It appears that the presence of certain MSAs confers susceptibility to specific clinical features, an association which reveals a serotype-phenotype relationship. In this review article we have provided a detailed summary of common and under-recognized cutaneous manifestations of DM.

Tofacitinib for the treatment of refractory pyoderma gangrenosum.

Pyoderma gangrenosum (PG) is a rare, debilitating, inflammatory skin disease associated with a variety of systemic diseases. Because of its rarity, PG is treated with miscellaneous immunosuppressive agents as there is no US Food and Drug Administration-approved standardized treatment approach. We present four patients with PG treated with tofacitinib in the context of the six existing cases in the literature. Tofacitinib appeared to be beneficial in the small sample of patients (n = 10) who failed an average of four other systemic therapies. The majority of patients had classic PG located on the legs (80%, 8/10), while 20% of cases (2/10) were peristomal. The most common comorbidity was inflammatory bowel disease (78%, 7/9). There were no negative treatment results and 40% (4/10) of patients had complete healing of their ulcers, while the other 60% (6/10) had marked clinical improvement. From our observation, tofacitinib appears to be a promising steroid-sparing adjuvant treatment in patients with refractory PG who have failed on other systemic therapies.