Ichthyosis, psoriasiform dermatitis, and recurrent fungal infections in patients with biallelic mutations in PERP.

BACKGROUND: Germline autosomal dominant and autosomal recessive mutations in PERP, encoding p53 effector related to PMP-22 (PERP), a component of epidermal desmosomes, have been associated with a spectrum of keratodermas. Monoallelic nonsense mutations cause Olmsted syndrome with severe periorificial keratoderma and palmoplantar keratoderma (PPK). Biallelic recessive frameshift and missense mutations are associated with milder forms of the disease, including generalised erythrokeratoderma and PPK. OBJECTIVES: To add new insights into the genotype-phenotype correlations as a consequence of PERP mutations and to provide a comprehensive review of the literature. METHODS: Among 26 previously unresolved families within a cohort of 180 extended Iranian families with syndromic or non-syndromic ichthyosis, two families with shared clinical features were examined by whole-exome sequencing and genome-wide homozygosity mapping. Mycological and dermatopathological studies were performed to further characterise their atypical phenotypic presentations. RESULTS: In two unrelated multiplex consanguineous families affected by ichthyosis, two novel biallelic PERP variants, NM_022121.5, c.89T > C, p.Leu30Pro and c.466G > C, p.Gly156Arg, located inside of genomic homozygosity regions of the probands were detected. Interestingly, some patients had areas of scaly psoriasiform plaques on the background of generalised ichthyosis that appeared during active cutaneous fungal infections. Mycological examinations of these lesions revealed infections caused by Candida albicans, Epidermophyton floccosum, or Trichophyton rubrum. Histopathology of the psoriasiform lesions shared some features with psoriasis, which when combined with clinical presentation, led to incorrect diagnosis of guttate psoriasis or pustular psoriasis. CONCLUSIONS: PERP variants in ichthyosis patients can confer susceptibility to recalcitrant cutaneous fungal infections. Additionally, patients with episodic psoriasiform dermatitis in the setting of keratoderma should be considered for PERP genotyping and cutaneous fungal examinations.

Loss of normal anagen hair in pemphigus vulgaris.

BACKGROUND: Pemphigus vulgaris (PV) is a known cause of loss of 'normal' anagen hair; that is, shedding of intact anagen hairs covered by root sheaths. However, studies on this subject are limited. AIM: To investigate anagen hair shedding in patients with PV, and ascertain its association with disease severity. METHODS: In total, 96 consecutive patients with PV (new patients or patients in relapse) who were admitted to the dermatology wards of a tertiary hospital were enrolled in this study. Demographic data, PV phenotype, disease severity and presence of scalp lesions were recorded. A group of 10-20 hairs were pulled gently from different areas of the scalp (lesional and nonlesional skin) in all patients, and anagen hairs were counted. Disease severity was graded according to Harman score. RESULTS: Anagen hair was obtained by pull test in 59 of the 96 patients (61.5%), of whom 2 had normal scalp. The mean ± SD anagen hair count was 5.9 ± 7.6 (range 0-31). In univariate analysis, anagen hair loss (P < 0.01) and the presence of scalp lesions (P = 0.01) were associated with severe disease. Mean anagen hair count was significantly higher in the severe (mean 6.83 ± 7.89) than the moderate (mean 1.06 ± 1.94) subgroup (P < 0.001). Multivariate analysis confirmed anagen hair loss (OR = 1.16, 95% CI = 1.05-1.28, P < 0.01), but not scalp lesions (P = 0.69) as an independent predictor of disease severity. CONCLUSIONS: According to our study, normal anagen effluvium is a frequent finding in patients with PV, and interestingly, this was observed in nonlesional as well as lesional scalp. In addition, severe anagen hair loss was an independent predictor of the disease severity.

Diagnostic accuracy of punch biopsy in subtyping basal cell carcinoma.

BACKGROUND: Basal cell carcinoma (BCC) is the most common skin cancer in humans. The histological subtype reported by punch biopsy may influence the type of treatment. Few studies have investigated the accuracy of punch biopsy in diagnosing the true BCC subtype. OBJECTIVE: To determine the accuracy, sensitivity and specificity of punch biopsy in BCC subtype diagnosis. METHODS: In this retrospective study, 333 biopsy specimens and excisions were reviewed. Histological subtypes present in the initial biopsy were compared with tumour subtypes of the total excision. RESULTS: The concordance between the BCC subtype present in the biopsy specimen and in the subsequent excision specimen was 72.3%. The most common BCC patterns were nodular (158, 47.5%) and mixed subtype (90, 27%). Most mixed tumours contained one or more aggressive subtype (63/90, 70%). In 47/120 (39.1%) aggressive tumours (14.1% of the total), punch biopsy failed to correctly identify the aggressive component. The most commonly missed aggressive subtype was mixed aggressive including nodular/micronodular and nodular/infiltrative (30/47, 63.8%). In 45/213 (21.1%) non-aggressive BCCs (13.5% of total cases), punch biopsy incorrectly reported an aggressive subtype. The most commonly misidentified non-aggressive subtype was nodular (39/45, 86.6). The sensitivity and specificity of punch biopsy in diagnosing aggressive vs. non-aggressive BCC subtypes 60.8% (95% CI, 51.9-69.1) and 78.9% (95% CI, 72.8-83.8), respectively. The positive and negative predictive values were 61.9% and 78.1%, respectively. CONCLUSION: Punch biopsy has serious pitfalls in differentiating aggressive and non-aggressive BCC subtypes. Dermatologists should consider the possibility of aggressive components within non-aggressive BCCs reported using punch biopsy.

Comparison of desmoglein 1 and 3 enzyme-linked immunosorbent assay and direct immunofluorescence for evaluation of immunological remission in pemphigus vulgaris.

BACKGROUND: Drug withdrawal is the ultimate goal in the management of patients with pemphigus. Direct immunofluorescence (DIF) has long been considered the gold-standard test to predict immunological remission in pemphigus vulgaris (PV); however, there have been no comparisons between DIF and antidesmoglein (anti-Dsg) ELISA. AIM: To compare anti-Dsg ELISA with DIF in patients with PV for evaluation of immunological remission. METHODS: The study enrolled 46 patients with PV who had absence of any lesion, and had a daily prednisolone dosage of ≤ 10 mg without adjuvant drug treatment in the preceding 6 months. Biopsy specimens were taken from patients and processed for DIF. Intercellular deposition of IgG and/or C3 was considered positive. Serum samples were also collected for anti-Dsg1 and anti-Dsg3 ELISA, and an ELISA index value of > 20.0 was considered positive. RESULTS: DIF and anti-Dsg ELISA were positive for 11 (23.9%) and 18 patients (39.1%), respectively. Anti-Dsg ELISA had a sensitivity of 100%, a specificity of 80%, a positive predictive value of 61.1% and a negative predictive value of 100%. CONCLUSIONS: The high sensitivity of anti-Dsg ELISA proves that this simple serological test is a good substitute for DIF for evaluation of immunological remission in PV. As none of the DIF-positive patients was anti-Dsg-negative, it is possible that during the course of immunological remission, results for DIF may become negative before the results for Dsg ELISA do so.

Trichophyton Schoenleinii-induced widespread tinea corporis mimicking parapsoriasis.

We report a case of extensive tinea corporis in an 80-year-old woman on her forearms, thighs, legs, buttocks and trunk, mimicking parapsoriasis due to Trichophyton schoenleinii, without scalp involvement. Diagnosis of Trichophyton schoenleinii was confirmed by microscopy and mycological culture specimens.

A study on plucked hair as a substrate for direct immunofluorescence in pemphigus vulgaris.

BACKGROUND: It has recently been demonstrated in a study on 15 patients that plucked hair can be used as a substrate for direct immunofluorescence (DIF) in pemphigus. OBJECTIVE: Our aim was to assess the sensitivity of DIF on plucked hairs in pemphigus vulgaris (PV) patients with positive DIF of oral mucosa. METHODS: One hundred and ten new PV patients were enrolled in the study. They all showed the typical clinical and histological findings as well as positive DIF of the oral mucosa, diagnostic for PV. Approximately 30 hairs were obtained in the same way as for the trichogram. The hairs with their outer root sheaths (ORS) were processed for DIF in order to detect immunoglobulin G and C3. RESULTS: Immunodeposits favouring PV were demonstrated in the ORS of 100 cases showing a sensitivity of 91%. CONCLUSION: Regarding the relatively high sensitivity of DIF on plucked hair in PV patients with positive oral mucosal DIF in our study, it seems that hair plucking is a suitable alternative to the more invasive techniques of skin or mucosal biopsy for obtaining specimens for DIF in PV.

Persistent periorbital edema as a sole manifestation of cutaneous lupus erythematosus: report of two cases.

In lupus erythematosus, dramatic periorbital edema and erythema without any evidence of other significant cutaneous or systemic involvement is unusual. We describe two patients with severe periorbital edema and erythema as the sole manifestation of cutaneous lupus erythematosus.

Diffuse plane xanthoma in an otherwise healthy woman.

We report a case of diffuse plane xanthoma in a 40-year-old otherwise healthy woman. Her disease began 18 years ago as xanthelasma and progressed to involve large areas of her face, neck and trunk. No associated diseases were detected on repeated laboratory testing.