Clinical and Experimental Dermatology最新文献

Background: Telogen effluvium (TE) is defined by an increased ratio of hairs in telogen to hairs in anagen. Diagnosis is not contingent on a self-reported quantum of telogen shedding. Androgenetic alopecia (AGA) is diagnosed histologically by follicular miniaturization. TE and AGA can both produce balding; however, their relative contributions and the sequence of these events are unknown.

Objectives: To correlate individual fibre diameter (a proxy for follicular miniaturization) with anagen and telogen duration to determine whether TE precedes or follows AGA.

Methods: Healthy men aged 18-55 years with stage 3-5 vertex balding had serial tattoo-directed phototrichograms on days 1, 84 and 112. Individual hairs were tracked with computer-assisted hair-to-hair matching. Fibre diameter was measured. Anagen and telogen duration were mathematically calculated using the fraction of anagen and telogen hairs that remained in the same cycle phase between follow-up examinations.

Results: There was a linear correlation between fibre diameter and anagen duration. Thin fibres (60 µm) had a shortened mean (SD) anagen duration of 200 (72) days. In balding scalps, thick anagen fibres (> 80 µm) also had a shortened mean anagen duration of 580 (150) days. Telogen duration did not vary with fibre diameter.

Conclusions: In men, a shortening of anagen duration precedes fibre diameter reduction. The clinical correlate of anagen shortening is TE, while reduction in fibre diameter correlates with follicle miniaturization and AGA. While visible TE occurs years in advance of visible balding in women with long hair, TE may go unnoticed in men with short hair. The observed sequence of events establishes that TE is a precursor to AGA. Failure to observe shedding does not negate a diagnosis of TE. We have developed a new model to describe the pathogenesis of balding.

Background: Pathogenic heterozygous desmoplakin (DSP) variants cause arrhythmogenic cardiomyopathy, predisposing to sudden cardiac death, and occasionally are found in dermatology patients with palmoplantar epidermal differentiation disorders (pEDDs) and curly/woolly hair. DSP variants of uncertain significance (VUS) in patients with pEDD complicate cardiac risk assessment.

Objectives: To characterize cardiocutaneous phenotypes associated with heterozygous DSP variants.

Methods: We enrolled 45 heterozygous DSP carriers [aged 2-80 years; 18 probands followed for cardiomyopathy (n = 16) or pEDD (n = 2) and 27 family members] and 10 family members who were noncarriers from 18 families at Helsinki University Hospital, Finland. Genetic, cardiac and dermatological evaluations included next-generation sequencing panels, whole exome or Sanger sequencing, laboratory tests, electrocardiography, echocardiography, cardiac magnetic resonance imaging, skin histology, immunohistochemistry and hair microscopy.

Results: Seventeen DSP variants (10 pathogenic/likely pathogenic, 7 VUS) were identified. Fifteen were newly associated with pEDD, including six also new for cardiomyopathy. Characteristic focal hyperkeratosis around heel rims and outer edges of soles (DSP-pEDD) was observed in 86% (36/42) of carriers, accompanied by palmar hyperkeratosis (36%, 15/42), pEDD-related pain (59%, 16/27), aquagenic whitening (58%, 19/33) and curly/wavy hair (57%, 24/42). Cardiac abnormalities occurred in 72% (31/43), with 60% (26/43) meeting cardiomyopathy criteria, 44% (19/43) exhibiting arrhythmias, and 16% (7/43) requiring resuscitation. VUS-associated phenotypes were similar to pathogenic/likely pathogenic variants. Onset of pEDD (median 13 years, range 1.5-70 years) preceded cardiomyopathy by three decades. Cardiac abnormalities affected 10% (3/29) of adults with pEDD by age 30, 52% (15/29) by age 50 and 83% (24/29) by age 70 years.

Conclusions: Heterozygous DSP variants cause childhood-onset focal pEDD preceding midlife-onset arrhythmogenic cardiomyopathy. Genetic testing is essential in pEDD and cardiac evaluation in patients with DSP variants.

Purpura fulminans (PF) is a dermatological emergency with a high mortality rate, characterized by extensive skin necrosis due to microvascular thrombosis. As a manifestation of systemic coagulopathy, PF is frequently associated with disseminated intravascular coagulation (DIC) and sepsis. Dermatologists play a crucial role in its early recognition and multidisciplinary management. This review aims to provide a comprehensive overview of PF, including its clinical presentation, classification, underlying pathophysiology, diagnosis and current management strategies. A systematic analysis of existing literature relating to PF was conducted, focusing on its clinical features, histopathology, laboratory investigations and treatment approaches. PF presents with painful, well-demarcated purpuric lesions that evolve into necrotic eschars. The disease is categorized into neonatal, postinfectious and acute infectious subtypes, with acute infectious PF being the most common. PF pathophysiology involves acquired or congenital deficiencies in proteins C and S, leading to unregulated thrombosis and vascular damage. Diagnosis requires a combination of clinical assessment, coagulation studies and histopathology. Management includes broad-spectrum antibiotics, coagulation support, protein C replacement (in neonatal patients), therapeutic plasma exchange and skin-directed treatments. Surgical intervention is often necessary for extensive necrosis. Given its life-threatening nature, PF demands heightened awareness in the dermatology community. Early diagnosis and prompt intervention can greatly improve outcomes. Strengthening interdisciplinary collaboration between dermatologists, intensivists and haematologists is essential for optimizing patient care and reducing mortality associated with PF.