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.

Correlation of anti-γ/ε nicotinic acetylcholine receptor antibody levels with anti-desmoglein 1,3 antibody levels and disease severity in pemphigus vulgaris.

BACKGROUND: A role for nondesmoglein antigens in the pathogenesis of pemphigus vulgaris (PV) has been suggested in several studies. Acetylcholine receptors (AchR), are one of the most important groups of these antigens. However, the exact role of both antimuscarinic (m) and nicotinic (n) AchR antibodies (Abs) is still controversial. AIM: To evaluate anti-desmoglein (Dsg)1, Dsg 3 and anti-γ/ε nAchR Abs values in patients with PV before and 3 months after rituximab (RTX) treatment, and to assess their correlation with disease severity. METHODS: In total, 75 patients with PV (26 men, 49 women) who were planned to receive RTX were enrolled. Disease activity was assessed by using the Pemphigus Disease Area Index (PDAI). Using ELISA, anti-Dsg1,3 and anti-γ/ε nAchR Abs were determined at baseline and 3 months after RTX treatment. RESULTS: At baseline, 53.33% patients had positive values for anti-Dsg1, 89.33% for anti-Dsg3 and 13.33% for anti-γ/ε nAchR Abs. All patients with positive anti-γ/ε nAchR Abs had the mucocutaneous phenotype. PDAI, anti-Dsg1,3 and anti-γ/ε nAchR values were dramatically decreased 3 months after RTX infusion (P < 0.001). There was a significant positive correlation between disease activity and anti-γ/ε nAchR values at baseline (P = 0.04), whereas no significant correlation was observed between anti-Dsg1,3 and anti-γ/ε nAchR values at baseline and 3 months after RTX infusion. CONCLUSION: The reduction in anti-γ/ε nAchR Abs with clinical improvement in this study may suggest a synergic role for anti-γ/ε nAchR Abs with anti-Dsg1,3 Abs, or it could be an epiphenomenon.

Inter-rater reliability of the BIOCHIP indirect immunofluorescence dermatology mosaic in bullous pemphigoid and pemphigus patients.

BACKGROUND: The BIOCHIP (Dermatology Mosaic 7; EUROIMMUN, Lubeck, Germany) is a novel multiplex indirect immunofluorescence (IIF) technique used in the serological diagnosis of bullous pemphigoid (BP) and pemphigus. OBJECTIVE: To validate the accuracy and inter-rater reliability (IRR) of the BIOCHIP in the diagnosis of BP, pemphigus foliaceus (PF) and pemphigus vulgaris (PV). METHODS: Sera from patients with BP (n = 38), PF (n = 8), PV (n = 23), control patients (n = 64) and healthy control volunteers (n = 39) were tested. Sera were collected and analysed during the course of the disease at 1-5 different time points. The BIOCHIP was performed for all patients, digital images were captured of each incubated field, and the images were shared with 10 dermatologists experienced in reading IF from around the world to report. There were 312 BIOCHIP slides consisting of 1872 photos in total. All patients were de-identified. Fleiss Kappa was used to estimate the IRR. RESULTS: Fleiss Kappa was computed for each category (Oesophagus, Oesophagus immunofluorescence pattern, Salt-Split Skin (SSS), SSS immunofluorescence location, BP180, BP230, Dsg 1 and Ds3). The inter-rater agreement between the 10 raters varied between fair and moderate for all categories. Those that demonstrated fair concordance included monkey oesophagus (k = 0.257, P < 0.0001), oesophagus pattern (k = 0.357, P < 0.0001), Dsg1 (k = 0.390, P < 0.0001) and BP230 (k = 0.281, P < 0.0001). Moderate agreement was demonstrated for SSS (k = 0.416, P < 0.0001), SSS immunofluorescence location (k = 0.505, P < 0.0001), Dsg3 (k = 0.437, P < 0.0001) and BP180 (k = 0.559, P < 0.0001). CONCLUSION: The BIOCHIP mosaic-based immunofluorescence test is a simple, time and effort saving test that can aid in the diagnosis and screening of BP, PV and PF. However, the level of agreement was relatively low. The authors found the most common causes to be variable levels of training, indicating the presence of a learning curve in the interpretation of the results and ambiguous staining patterns leading to incongruent results.

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.

Association of Human Herpes Virus 6 Infection with Lichen Planopilaris.

Lichen planopilaris (LPP) is the prototype of cicatricial alopecia and is the follicular form of lichen planus. Some studies showed viral agents such as hepatitis C virus; Epstein Bar virus and human Herpes viruses are associated with classic and oral lichen planus. We conducted this study to find if there is a relationship between LPP and human herpes virus-6 (HHV-6) as this virus is prevalent worldwide. This cross-sectional study was conducted in Razi Hospital, Tehran, during one-year interval. Total of 30 treatment naïve LPP patients and 30 healthy matched controls enrolled the study. Serum anti-HHV-6 antibody and the presence of virus genome examined using ELISA and Nested PCR technique, respectively. HHV-6 genome was also determined three months after treatment in LPP patients. Twenty-nine (96.6%) and 3(10%) of LPP patients were positive for anti-HHV-6 antibody and DNA genome, respectively; while 28(93.3%) and 3(10%) were positive in the control group. The presence of anti-HHV-6 antibody and HHV-6 genome was not statistically different between LPP patients and controls (p value >0.05). The comparison between LPP cases after three months of systemic therapies and the same controls also showed no statistically significant difference (P value >0.05). This study showed there is no association between lichen planopilaris and HHV-6.

Self-healing Langerhans cell histiocytosis (Hashimoto-Pritzker disease): two Tunisian cases.

Self-healing Langerhans cell histiocytosis (SHLCH) is a rare self-limited variant of Langerhans cell histiocytosis that presents at birth or during the neonatal period. It was first described by Hashimoto and Pritzker in 1973. Subsequently, more than 70 cases have been reported in the literature. Regarding age of onset, SHLCH should be divided into congenital SHLCH and rare late-onset type. We report here two additional cases of SHLCH in Tunisian infants. We emphasize the need for long-term follow-up in such patients.

Cryotherapy plus oral zinc sulfate versus cryotherapy plus placebo to treat common warts: A double blind, randomized, placebo-controlled trial.

BACKGROUND: Cutaneous warts are caused by a small group of specific types of human papillomaviruses. Cryotherapy is a highly effective treatment for patients with viral warts; however, it is a painful method and usually requires several treatment sessions. Zinc is a trace element with many proven effects on the immune system. OBJECTIVE: Our aim was to assess the efficacy and safety of oral zinc sulfate in the treatment and recurrence rate of common warts. METHODS: Eighty-three patients with common warts participated in this double-blind, randomized, placebo-controlled trial. In both groups, three sessions of liquid nitrogen cryotherapy were performed for up to 2 months with 3-week intervals. The treatment group (n = 45) received oral zinc sulfate capsules in a dose of 10 mg/kg per day up to 600 mg day. The control group (n = 38) was provided with placebo of similar appearance. Treatment continued for 2 months and the follow-up period lasted up to 6 months. RESULTS: Warts completely resolved in 26 patients in the treatment group (68.4%) and 23 patients in the placebo group (63.9%; p = .68). Three patients (7.9%) in the treatment group and six patients (16.6%) in the placebo group has a recurrence of the warts (p = .19). CONCLUSION: According to our study, the addition of zinc to cryotherapy was not beneficial in the treatment of patients with common warts nor did it prevent recurrences.

Two measurement methods of motor ulnar nerve conduction velocity at the elbow: a comparative study.

BACKGROUND: Electrodiagnostically, localization of ulnar nerve lesions, which commonly occurs at the elbow, is sometimes problematic. Measurement of motor ulnar nerve conduction velocity (NCV) at the elbow is amongst the most popular techniques to diagnose ulnar neuropathy. In this method, recording from the first dorsal interosseous muscle (FDI) is suggested to be more sensitive than the abductor digiti minimi (ADM). However, the criterion for abnormality is based on the normal values recorded from ADM. AIMS: To determine the normal values of Ulnar motor NCV using FDI and ADM and the difference between the values obtained from FDI and ADM. Additionally, to measure the amount of reduction of NCV across the elbow for each recording site. MATERIALS AND METHODS: This was a cross-sectional study performed on 50 healthy volunteers (100 nerves). All subjects were in the same condition regarding joint position and surface hand temperature. We recorded ulnar NCV at forearm and across the elbow with recording electrode on both FDI and ADM, simultaneously. RESULTS AND CONCLUSIONS: The mean NCV at the elbow recorded from ADM and FDI were 62.65 +/- 7.62 m/s and 60.49 +/- 7.42 m/s respectively, showing significant difference. The ulnar minimum normal NCVs recorded from ADM and FDI were 47.4 m/s and 45.6 m/s, respectively. If the normal values of ADM are used as the basis for recording from FDI, it could lead to false-positive diagnosis of cases suspicious of ulnar neuropathy. Therefore it is preferred to use the normal values of FDI itself while recording.

Persistent lip enlargement: An unusual presentation of lupus erythematosus.

Macrocheilia is a challenging problem with a variety of underlying causes that are both local and systemic, and granulomatous causes underlie the majority of cases. In this study, we report on a 31-year old man who presented with a chronic lower lip enlargement and a nodular submental erythematous lesion. He was otherwise clinically healthy. Laboratory test results were within the normal limit except for a positive anti-double stranded DNA test result. A diagnosis of cutaneous lupus erythematosus was made on the basis of histopathology and direct immunofluorescence. The lesions resolved dramatically after treatment with hydroxychloroquine. Lupus erythematosus should be considered when examining patients who present with chronic lip swelling.

Thenar muscles H reflex in patients with fibromyalgia: A case control study.

OBJECTIVE: To delineate H-reflex parameters and specify the diagnostic accuracy measures of thenar muscle H-reflex in Fibromyalgia (FM). METHODS: The study was a cross sectional study performed on 30 subjects with FM and 30 healthy volunteers in two major referral hospitals. We recorded the number of obtainable thenar H-reflexes and their minimum latency, threshold and amplitude in each group. RESULTS: There was a significantly more chance to elicit the H-reflex in patients with FM. H reflex threshold and minimum latency were lower in FM group but no significant difference was shown for H wave amplitude. According to our study, thenar H-reflex has 46.7% sensitivity, 86.7% specificity and 66.7% diagnostic accuracy to detect FM. It also has moderate predictive values and positive likelihood ratio but low negative likelihood ratio. CONCLUSION: Higher rate of thenar muscle H-reflex in fibromyalgia can be interpreted as a confirmatory finding to central sensitization theory for this disorder. Obtaining H-reflex from thenar muscles could be a helpful diagnostic tool for fibromyalgia that increases the confidence in diagnosis. Although it is a weak tool for screening because of low sensitivity, it has a relatively high specificity.

Effects of in ovo injection of bovine lactoferrin before incubation in layer breeder eggs on tibia measurements and performance of laying hens.

There is increasing concern about welfare of laying hens in cages, and one aspect of this topic relates to bone fragility. Therefore, bone anabolic components such as bovine lactoferrin (bLF) may be an effective strategy to maintain the integrity and health of bones. A total of 1080 eggs were divided into four groups with three replicates, each comprising 270 eggs; (1) control group was injected with 100 µl of normal saline per egg; (2, 3 and 4) groups including 22.5 (low), 45 (medium) and 67.5 µg (high) of bLF in 100 µl of normal saline per egg. Eggs were incubated and after hatching, chicks were reared to 28 weeks of age. Tibia measurements were obtained at hatch and at 28 weeks of age. Tibia weight at hatch, was not influenced by in ovo injection of bLF in comparison with the control. Eggs injected with the high concentration of bLF (67.5 µg of bLF per egg) showed significant strengthening in laying-hen tibias at 28 weeks of age, as measured by ultimate force and bending stress, compared with the control. Egg weights from hens treated with this concentration of bLF were also significantly greater than the control. Our data suggest that tibia cortical thickness is a suitable variable for evaluating bone status reflecting bone integrity and strength. The present study also shows that bLF (67.5 µg of bLF per egg) injected into layer breeder eggs before incubation can be used to improve bone strength and egg weight of laying hens at 28 weeks of age, while having no detrimental effect on embryo hatchability.

[Solid cystic papillary tumor of the pancreas]. / Tumeur papillaire solide et kystique du pancréas.

Solid cystic papillary tumors of the pancreas are rare; they occur most commonly in young women. Despite their characteristic microscopic appearance, their immunophenotype is not specific. Their prognosis is excellent after complete surgical resection. The study aim was to report two cases in female patients who were 15 and 20 years old; the first tumor was discovered fortuitously and the second girl presented with abdominal pain and vomiting. Both tumors were encapsulated and located in the tail of the pancreas. The histological study showed the papillary architecture mixed with solid areas. Immunohistochemical staining was positive only for vimentin in one case and positive for cytokeratin, chromogranin, synaptophysin, neuron specific enolase, vimentin and protein S100 in the second case.