miRNA implication in the pathogenesis and the outcome of Tunisian endemic pemphigus foliaceus.

Pemphigus foliaceus (PF) is a bullous autoimmune skin disease diagnosed through sera and skin analyses. PF severity is associated with maintained anti-Dsg1 sera levels and its prognosis is unpredictable. MicroRNA (miRNA), dynamic regulators of immune function, have been identified as potential biomarkers for some autoimmune diseases. This study aimed to assess the miRNA expression of miR-17-5p, miR-21-5p, miR-146a-5p, miR-155-5p and miR-338-3p using quantitative real-time PCR in peripheral blood mononuclear cells (PBMC) and lesional skin samples from untreated and treated PF patients (both remittent and chronic) over 3 months. Overall, miRNA expression was significantly higher in PBMC than in biopsy samples. Blood miR-21 expression was increased in untreated patients compared to controls and had a diagnostic value with an AUC of 0.78. After 6 weeks, it decreased significantly, similar to anti-Dsg1 antibodies and the PDAI score. In addition, a positive correlation was observed between cutaneous miR-21 expression and the disease activity score. Conversely, cutaneous expressions of miR-17, miR-146a and miR-155 were significantly higher in treated chronic patients compared to remittent ones. The cutaneous level of miR-155 positively correlated with pemphigus activity, making it a potential predictive marker for patients' clinical stratification with an AUC of 0.86.These findings suggest that blood miR-21 and cutaneous miR-155 can be used as supplemental markers for PF diagnosis and activity, respectively in addition to classical parameters.

Pustular psoriasis of pregnancy: Clinical and genetic characteristics in a series of eight patients and review of the literature.

Pustular psoriasis of pregnancy (PPP) can lead to life-threatening complications. The objective of this study is to report clinical and genetic spectrum, prognostic factors and management options. A retrospective study was designed including eight PPP patients. Clinical data were collected, and performed genetic and statistical analysis to identify factors associated with fetal complications, resistance to treatment and post-partum flare extension. A systematic review of the literature was also carried out. Eight Tunisian patients, with a mean age of 23 ± 3.3 years, were included. They presented 14 flares (F) during pregnancies and one flare after delivery. Additional GPP flares outside pregnancy periods were noted in 2/8 of patients. The mean duration of PPP flares was 16.66 ± 7.8 weeks. The first flare occurred at a gestational age of 26 ± 5 weeks. Only 2/8 studied patients presented a homozygous mutation c.80 T > C (p.L27P) in IL36RN gene. Used treatments were topical steroids (n = 12F), systemic steroids (n = 5F), ciclosporin (n = 1F), UVB (n = 1F) and acitretin (in post-partum n = 6F). Complications were oligoamnios (n = 2), intra-uterine growth retardation (n = 1), fetal death in utero (n = 1), prematurity (n = 3), low weight at birth (n = 2). A significant association was found between (i) occurrence of fetal complications and early gestational age at the onset (p = 0.036), (ii) resistance to topical steroids and body surface affected area (p = 0.008), (iii) presence of mutation c.80 T > C in PPP flares and low serum levels of calcium (p = 0.01). Our systematic review of the literature identified 39 patients with 41 flares of PPP. Only 7/39 patients presented a causative mutation in IL36RN and CARD14 genes. PPP is characterized by a phenotypic heterogeneity and can be associated to IL36RN mutations. Its early onset can be associated with fetal complications. Systemic steroids and cyclosporine remain the most used therapies.

Hymenal polyps in two infants.

Pathological conditions of the hymen are rare in everyday medical practice. Hymenal polyps are polypoid formations originating from the hymenal rim and are benign and disappear spontaneously within a few weeks of onset. We report two cases of hymenal polyps in two infants.

Oxalosis in a Patient with Livedo Reticularis.

A 27-year-old man with terminal renal failure requiring peritoneal dialysis for the past 2 years was referred to the dermatologist for evaluation of red violaceous macular skin lesions consistent with livedo reticularis. These lesions had appeared suddenly on his legs (Figure 1). He had first experienced recurrent nephrolithiasis at the age of 14. Results from urine analysis and abdominal ultrasound revealed chronic kidney failure. Because the patient had a sister with similar findings, primary hyperoxaluria (PH) was suspected and genetic testing was performed in all members of his family. The results confirmed PH type 1 (PH1) in both our patient and his sister, who had died 8 years after the establishment of the diagnosis. A biopsy of the livedo reticularis lesions revealed deposits of a yellowish brown crystalline material within the lumen and the media of medium vessels in the hypodermis associated with a histiocytic giant cell reaction (Figure 2a). There was no evidence of extravascular calcium deposition in the sections examined. The deposits were intensely birefringent under polarized light, and classic speculated crystals of oxalate salts were observed (Figure 2b). No focal epidermal or superficial dermal necrosis was seen. On the basis of the histopathologic findings, the diagnosis of oxalate crystal-induced vascular disease was established. The patient subsequently developed complications including pancreatitis and peritonitis. He underwent hemodialysis until a combined liver-kidney transplant could be performed.

[Eosinophilic cellulitis: About a new pediatric case]. / Cellulite à éosinophile : à propos d'un nouveau cas pédiatrique.

Wells' syndrome or "eosinophilic cellulitis" is characterized by clinical features of cellulitis and histological pictures of eosinophils infiltrate of the dermis with some « flame ¼ figures. This is a very rare disease in the pediatric age. We report the case of a 14-month-old boy, presented with two farms painful nodular brownish lesions in the thigh and back of the foot as well as multiple erythematous papular and vesicular lesions on the forehead, cheeks, limbs and trunk. Biological analysis and histological examination confirmed the diagnosis of Wells' syndrome. The outcome was favorable with dermocorticoid.

Characteristics of DRESS Syndrome in the Elderly: A Comparative Study of 55 Patients.

Background: Drug reaction with eosinophilia and systemic symptoms (DRESS) is a rare drug reaction characterized by a skin rash, eosinophilia, and organ involvement. Objective: Our purpose is to focus on the clinical and epidemiological characteristics of DRESS in the elderly and to identify the incriminated drugs. Methods: This is a retrospective study including patients, hospitalized for DRESS with a RegiSCAR ≥4. The population was divided into 2 groups according to age: 65 years or older (G1) and <65 years (G2). The statistical study was performed using the comparative and multivariate analysis. Results: We included 55 patients (30.9% G1 and 69.1% G2). Skin manifestations were comparable in both groups. Lymphadenopathy was less common in G1 with a statistically significant difference (P = 0.012). Renal impairment was more frequent in the elderly with a statistically significant result (P = 0.005). DRESS in the elderly group was significantly associated with the occurrence of sepsis (P = 0.008). Allopurinol was the most common culprit associated with DRESS in G1 (P = 0.001). Relapses and recurrences were comparable in both groups (P = 0.71). Conclusions: DRESS in the elderly is associated with a high risk of complications, mainly kidney involvement and sepsis. Allopurinol is the most incriminated drug.

Exploring the role of vitamin D-VDR pathway in pemphigus foliaceous: a novel perspective on disease pathogenesis.

Several auto-immune diseases have been linked to vitamin D deficiency as a contributing environmental factor. Its pleiotropic effects on the immune system, especially its essential role in maintaining immune tolerance, make the vitamin D pathway of great interest. In this study, we focused on Pemphigus foliaceous (PF) in Tunisian population. we aimed to quantify the Serum 25[OH]D levels using chemiluminescence assay and to analyze the differential expression of the VDR, CYP27B1 and CYP24A1 genes in the circulating blood cells and lesional skin tissue of PF patients using Q-PCR. A genetic explanation was then sought to explore any direct relationship between tag polymorphisms and the inherited features of PF. Results confirmed a vitamin D hypovitaminosis in Tunisian PF patients. Interestingly, a differential gene expression correlated to the disease stratification was noted. Indeed, at the systemic level, an upregulation of VDR and CYP27B1 genes was observed in healthy controls compared to PF patients. Notably, in lesional skin tissue, the clinical and serological remission phase was correlated with high transcriptional levels of the VDR gene and conversely a drop in expression of the CYP24A1 gene. Genetic analysis indicated the involvement of the most appealing polymorphisms, rs2228570 and poly (A) microsatellite, in PF etiopathogenesis. Indeed, CAC13 haplotype was associated with a higher risk of PF development. Our findings suggest that alterations in the vitamin D-VDR pathway may influence PF physiopathology, making this pathway a potential target for pharmacological modulation, especially for cortico-resistant PF patients.

Direct medical cost related to the management of pemphigus: A pilot Tunisian study.

INTRODUCTION: Pemphigus is a therapeutically challenging disease with high morbidity and economic burden. First-line prescription of rituximab remains limited in Tunisia due to its high cost. Systemic steroids remain the standard of care but are associated with a major risk of morbidities and higher treatment costs. AIM: To assess the direct medical costs of pemphigus in Tunisia. METHODS: Retrospective estimation of direct medical costs during the 18 months following the diagnosis using the "bottom-up approach" in the Dermatology Department of Hedi Chaker Hospital, Sfax, Tunisia. RESULTS: Total medical costs were estimated at 38745.7 €, with an average cost of 1 210 € per patient and per year: paraclinical investigations (46%), medical treatment (30%), hospitalization (21%) and outpatient visits (3%). The average cost was the highest in the age group of 15-24 years (1553 €). Treatment costs related to corticosteroid-induced morbidity were estimated at 1208 €. CONCLUSIONS: The management of pemphigus in Tunisia needs to be adapted to take into account the health economic analysis in order to reduce overall disease costs and the burden of steroid-induced morbidities.

Unraveling the role of the vitamin D-VDR pathway in pemphigus vulgaris from Tunisian patients.

Vitamin D dysregulation has been recognized as a factor that may cause or aggravate autoimmunity. Vitamin D deficiency was found to be common in pemphigus vulgaris (PV) in different populations. This study aimed to investigate the vitamin D-VDR pathway in PV in the Tunisian population. A serological study was carried out to determine the vitamin D status in newly diagnosed PV patients. CYP27B1, CYP24A1 and VDR mRNA expression was assessed using quantitative real-time PCR in peripheral blood mononuclear cells (PBMC) from untreated newly diagnosed and treated PV patients. In addition, a genetic study was accomplished on VDR polymorphisms to investigate the changes in VDR gene expression. Overall, the serological study confirmed the hypovitaminosis D in newly diagnosed PV patients. Vitamin D-VDR pathway gene expression showed downregulation of CYP27B1 and CYP24A1 mRNA in first-discovery patients compared to healthy controls, while VDR mRNA was highly expressed in newly diagnosed PV patients. Moreover, CYP27B1, CYP24A1 and VDR mRNA were significantly upregulated in chronic disease severity groups compared to mild disease groups. The genetic study showed low VDR gene expression in carriers of FokI > CC genotype, which was more frequent among PV patients, and FokI > C-TaqI > C-ApaI > A-polyA > A16 haplotype, suggesting that the VDR gene polymorphisms testing can provide useful information for PV treatment decision-making. In conclusion, our findings underline the impact of vitamin D-VDR pathway disruption in the PV pathophysiology in Tunisian patients.

An unusual pigmented skin lesion on the nipple-areola area.

Considering the rarity and underdiagnoses of this disorder, a pigmented and hyperkeratotic skin lesion located on the trunk, resembling to acanthosis nigricans should always be investigated for terra firma-forme dermatosis (TFFD) and thus alcohol must be applied. TFFD should be known among dermatologists and can be easily diagnosed and treated with isopropyl alcohol.

Unusual malar rash with ulceration: What can we expect?

Considering the clinical polymorphism of the disease, longstanding skin lesions located on the face, resembling erysipelas in an endemic area should always be investigated for CL and thus, atypical presentations should be kept in mind.

Role of chemical exposure in the incidence of vitiligo: a case-control study in Tunisia.

Vitiligo is a multifactorial dermatosis with many etiological hypotheses that have been suggested for its occurrence. To our knowledge, few epidemiological studies are available on vitiligo induction factors and particularly on the role of exposure to chemicals in the onset of the disease has been found. Therefore, there is need to investigate the relationship between vitiligo and chemical exposures in order to understand this mysterious disease. We conducted a case-control study of patients with vitiligo whose diagnosis was made by a specialist in dermatology. The total study period was of 6 months extending from 1 July to 31 December 2019. The minimum sample size was determined as 46 cases and 92 controls. The control group was gender, age, and professional status matched to the vitiligo group. In the binary logistic regression model, household chemicals/colored toothpaste use, a history of a repeated antibiotic use, and an occupational exposure to phenol/catechol derivatives were significantly associated with vitiligo (three to fourfold increase). Our results suggest that chemical factors play a key role in the occurrence of vitiligo. Therefore, prevention of this dermatosis requires the identification of exposure to the incriminated chemicals in any patient followed for vitiligo. The earlier the diagnosis of 'chemical' or chemically aggravated vitiligo, the better the prognosis for this disease.

Trichofolliculoma: A Case Series.

Trichofolliculoma (TF) is a rare benign adnexal follicular tumor, described as hamartoma with follicular differentiation according to some authors. It typically appears during adulthood on the face or scalp as an isolated nodule with protrusion of central tufted hairs. We present a retrospective series of eleven patients with histologically confirmed TF to evaluate epidemiological, clinical, and histopathologic characteristics. The mean age at excision was 46 years with extremes ranging from 20 to 75 years. The sex ratio M/F was 0.37. Clinical presentation was a papule or nodule with an average diameter of 6,7mm (2-15 mm), firm with central pit in 54 percent and visible emerging vellus hairs in 18 percent of cases only. The localization was on the face in seven cases (63.6%) and only four cases were located outside the face (scalp [n=2], sub mammary fold [n=1] and shoulder [n=1]). Histologically, a cystically dilated hair follicle containing keratinous material with several mature and immature branched follicular structures is described in all cases. According to our series, TF occurs predominantly in women without age predilection, in the face. Central tufted hairs are only found in a minority of cases corresponding histologically to many secondary vellus hair follicles. In fact, histopathological examination is the gold standard for the diagnosis because clinical diagnosis could be challenging. Histology and dermoscopy may vary according to the age of the lesion. To date, only few case series have been published.

Follicular Basaloid Hamartoma and Associated Cutaneous Tumors: Clinical, Histopathological and Dermoscopic Aspects.

Background: Basaloid follicular hamartoma is an uncommun benign neoplasm of the hair follicule. The linear form of basaloid follicular hamartoma can be associated with basal cell carcinoma.OBJECTIVE: We report a case of a patient with multiple basal cell carcinomas developing on a congenital lesion allowing the diagnosis of basaloid follicular hamartoma on histopathology. Methods: Each lesion was evaluated by two dermatologists. All biopsy specimens were routinely stained with hematoxylin-eosin. Results: A 76 year-old-man consulted our dermatology departement for erythematous papules spread over the left lower limb. The lesion had been evolving since birth with flesh-colored to pinkish papules following Blaschko's lines from the root of the thigh to the foot. Three months before consultation, the papules increased in size leading to nodules with sometimes an ulcerated center. Dermoscopy under polarized mode displayed for ulcerated lesions (A) yellow-brownish crusts and ulceration surrounded by blue-grey ovoid nests, subtle short white streaks, brown dots and linear/arborising vessels. For nodular lesions (B), dermoscopic features are white pinkish hue, dotted and linear vessels, brown dots, blue-grey structureless areas and white prominent shiny streaks. There were some more erythematous inflamed and eroded areas in the background with a reversed honeycomb white network on dermoscopy (C), polymorphous vessels, whitish scales, ulcerations and milia-like cysts. The background lesion showed varied dermoscopic structures on a flesh colored slightly pinkish bottom (D). Histolopathology concluded for lesions A to an infiltrating and nodular basal cell carcinoma, (B) and (C) to fibroepithelioma of Pinkus and (D) to basaloid follicular hamartoma. Conclusion: Several case reports have documented dermoscopic features of a solitary basaloid follicular hamartoma. However, further studies are required to specify any reproducible features.

Slow-growing pedunculated nodule.

There have been limited reported cases of pedunculated basal cell carcinoma(BCC). Our case is original, and it combines two rare aspects of CBC: Pedunculated and giant. This uncommon aspect is rarely encountered.