Unilateral Onychodystrophy and Puffy Fingers: Think about Carpal Tunnel Syndrome.

An 87-year-old man was referred to our department for evaluation of his dystrophic left fingernails that developed progressively for the past 2 years. His past medical history included hemodialysis for 10 years for chronic renal failure. Examination of his nails revealed xanthonychia, onycholysis, Beau's lines, and marked hyperkeratosis of the nail plate involving all of his left fingernails. However, his right fingernails were not affected (Figure 1). He also had edema of the left hand associated with puffy fingers but without trophic disorders (Figure 2). Mycologic exam-ination with direct microscopy and culture of his affected nails were negative. Antinuclear antibodies (ANAs), Scl-70 (anti-topoisomerase) antibodies, anti-centromere antibodies, and anti-RNA polymerase III antibodies were all negative. Capillaroscopy showed no abnormalities. An X-ray of his left hand showed no bony abnormalities. For the past 5 years, the patient had suffered from paresthesia and numbness on the left hand in the area of the median nerve. Paresthesia, pain, burning, and tingling involved mainly the thumb, plus the index and middle fingers, but not the little finger. Carpal tunnel syndrome (CTS) was suspected. Neurologic examination and electromyography (EMG) confirmed the diagnosis of CTS of the left hand explaining his unilateral onychodystrophy. The patient was then referred to a hand surgeon for his CTS.

Subcutaneous Nodules of the Vulva.

A 32-year-old patient complained of three slow-growing subcutaneous nodules on her right labius majus, present for 3 years. Her past medical history was unremarkable. Cutaneous examination revealed three subcutaneous nodules of 1 cm diameter firmly adherent to the underlying tissues, located on her right labium majorum (Figure 1). Regional lymph nodes were not enlarged. She underwent an excision biopsy of a subcuta-neous nodule under local anesthesia. The gross specimen was firm, white and fleshy in appearance. A skin biopsy was performed, and histological findings revealed a non-encapsulated dermal nodule composed of clusters of polygonal cells with small central nuclei and abundant eosinophilic cytoplasm (Figure 2a). The tumor cells formed sheets and nests irregularly infiltrating between collagen bundles. There was no significant cyto-logic atypia and mitotic features. There were no necrosis and hemorrhage. The cells were positive for S-100 immunostain (Figure 2b). Hence, the diagnosis of benign vulvar granular cell tumor was assessed. The patient underwent surgical excision of the subcutaneous nodules with no recurrence at 2 years.

Chronic Blepharitis: Consider Tinea Blepharo-Ciliaris.

A 7-year-old girl with a history of being in contact with a cat was referred to our department due to her 1-month unilateral blepharitis that was initially treated as a herpetic infection without amelioration. She experienced itching and loss of her right eyelashes (Figure 1). Her visual acuity was 20/20. The slit lamp examination revealed anterior blepharitis with madarosis, broken eyelashes, and lesions in right lower eyelid, while the left eyelids were normal.

Alopecia patterns and trichoscopic findings in patients with autosomal recessive congenital ichthyosis.

Background: Autosomal recessive congenital ichthyosis (ARCI) is a rare genodermatosis categorized among nonsyndromic ichthyoses. While ARCI patients often manifest hair abnormalities, their impact on the quality of life remains underreported in the literature. Objective: This study aims to comprehensively characterize the clinical and trichoscopic findings of alopecia in ARCI patients. Methods: A prospective study spanning from January 2019 to December 2021 (3 years) was conducted at the Dermatology Department of Habib Thameur Hospital, Tunis, Tunisia. Clinical and trichoscopic examinations were performed on the hair of the participants, with molecular studies conducted on 15 patients. Results: The study included 30 patients, predominantly female (male/female = 0.58), with a mean age of 20 years. Twenty-eight patients were born from consanguineous marriages. Lamellar ichthyosis was observed in 22 cases, while congenital ichthyosiform erythroderma and bathing suit ichthyosis were each present in 4 cases. The ARCI severity score, assessed using the Visual Index For Ichthyosis Severity scale, had a mean value of 15 (4-28). Alopecia emerged as a prominent finding in 11 patients, presenting as hairline recession (13%), multiple patchy alopecia (27%), and alopecia of the eyebrows (13%). Trichoscopic findings included interfollicular and perifollicular scaling, perifollicular lamellar hyperkeratosis, peripilar casts, interfollicular erythema, loss of hair openings, predominance of single hair follicles, broken hair, vellus hair, anisotrichosis, pili torti, dystrophic hair, and comma hair. Several trichoscopic findings showed statistically significant associations with the severity of ARCI. Limitations: In our study, we only included 30 patients due to the rarity of this genodermatosis. Conclusion: Contrary to previous perceptions, alopecia is a notable finding in ARCI, particularly in patients with a severe form. This study provides a detailed characterization of alopecia in ARCI, shedding light on its prevalence and associated trichoscopic features, thereby enhancing our understanding of this dermatological condition.

Corrigendum: Current phenotypic and genetic spectrum of syndromic deafness in Tunisia: paving the way for precision auditory health.

[This corrects the article DOI: 10.3389/fgene.2024.1384094.].

Current phenotypic and genetic spectrum of syndromic deafness in Tunisia: paving the way for precision auditory health.

Hearing impairment (HI) is a prevalent neurosensory condition globally, impacting 5% of the population, with over 50% of congenital cases attributed to genetic etiologies. In Tunisia, HI underdiagnosis prevails, primarily due to limited access to comprehensive clinical tools, particularly for syndromic deafness (SD), characterized by clinical and genetic heterogeneity. This study aimed to uncover the SD spectrum through a 14-year investigation of a Tunisian cohort encompassing over 700 patients from four referral centers (2007-2021). Employing Sanger sequencing, Targeted Panel Gene Sequencing, and Whole Exome Sequencing, genetic analysis in 30 SD patients identified diagnoses such as Usher syndrome, Waardenburg syndrome, cranio-facial-hand-deafness syndrome, and H syndrome. This latter is a rare genodermatosis characterized by HI, hyperpigmentation, hypertrichosis, and systemic manifestations. A meta-analysis integrating our findings with existing data revealed that nearly 50% of Tunisian SD cases corresponded to rare inherited metabolic disorders. Distinguishing between non-syndromic and syndromic HI poses a challenge, where the age of onset and progression of features significantly impact accurate diagnoses. Despite advancements in local genetic characterization capabilities, certain ultra-rare forms of SD remain underdiagnosed. This research contributes critical insights to inform molecular diagnosis approaches for SD in Tunisia and the broader North-African region, thereby facilitating informed decision-making in clinical practice.

Nail involvement in connective tissue diseases: an epidemiological, clinical, and dermoscopic study.

BACKGROUND: The assessment of nail changes in connective tissue diseases (CTD) has been rarely explored in previous studies. The use of dermoscopy to study vascular changes in nailfolds is an interesting diagnostic technique. The aim of the study was to describe the epidemiological, clinical, and dermoscopic features of nail lesions in CTD. METHODS: A prospective study was performed at the Dermatology Department of Habib Thameur Hospital (Tunis, Tunisia) in collaboration with the Internal Medicine Department over a period of 15 months, from July 2020 to September 2021, including patients diagnosed with systemic sclerosis (SS), systemic lupus erythematosus (SLE) and dermatomyositis (DM). RESULTS: Our study included 48 patients. Nail involvement was found in 44 cases. Dermoscopic nailfold abnormalities were identified in 37 cases. The most common clinical features were ragged cuticle, nailfold erythema, and onycholysis. Additionally, splinter hemorrhage, longitudinal ridging, lunula abnormalities, melanonychia, trachyonychia, leukonychia, increase in transverse curvature, parrot beak nail, half and half nails, and onychorrhexis were described. Nailfold dermoscopy showed a normal pattern in 10 cases, a nonspecific pattern in nine cases (SLE), and a scleroderma pattern in 29 cases (SS and DM). The scleroderma pattern was further categorized into an early pattern (6), an active pattern (14), and a late pattern (9). Normal pattern was observed solely in patients in remission. The late scleroderma pattern was associated with disease duration and systemic involvement. In SLE, disease activity correlated with onycholysis, nailfold erythema, and pathologic pattern in dermoscopy. However, patients with DM displayed a positive correlation between pulmonary involvement and scleroderma pattern. CONCLUSION: Nail involvement in CTD includes a diverse range of abnormalities. Despite being nonspecific, it can provide crucial clues for establishing a diagnosis. Nailfold dermoscopy serves as a mirror for microangiopathy, enabling the detection of changes at an initial stage, and thus, it becomes a diagnostic and prognostic tool.

Cutaneous Metastases: Clinicopathologic Study of 30 Patients.

Cutaneous metastases (CMs) of internal malignancies are uncommon. The breast in women and the lung in men represent the two elective sites of internal malignancies metastasizing to the skin. The aim of this study was to determine the epidemiologic, clinical, and pathologic features of CMs. A retrospective study of the patients diagnosed with CMs over 30 years was conducted. Thirty cases of CMs were enrolled in our study. In 16 cases (53%), the skin metastasis revealed the internal malignancy. The mean age was 66.4 years with sex ratio men/women of 2. CMs were solitary in 18 cases and multiple in 14 cases. The most frequent location was the chest (12 cases), followed by the abdomen (eight cases), the scalp (seven cases), and the arms (six cases). The common sites of primary malignancy were the lungs in men (nine cases) and the breast in women (three cases). Nine out of 30 patients died with an average of 33 months after diagnosis. In our study, the most frequent primary malignancy in men was lung cancer and in women breast cancer. The onset of CMs during the course of internal malignancy worsens the prognosis of the disease.

Comorbidity of bathing suit ichthyosis and limb-girdle muscular dystrophy type 2 A in a Tunisian patient revealed by Whole Exome Sequencing.

Elevated rates of consanguinity and inbreeding are responsible for the high prevalence of recessively inherited diseases among inbred populations including Tunisia. In addition, the co-occurrence of two of these conditions, called also comorbidity, within the same individual or in members of the same family are often described in Tunisia which is challenging for diagnosis. The high throughput sequencing has improved the diagnosis of inherited diseases. We report here on a 32-year-old woman born to consanguineous parents. She presented with congenital ichthyosis and muscular dystrophy. She was primarily suspected as suffering from Chanarin-Dorfman syndrome (CDS) with unusual form. Screening of founder mutations allowed only the elucidation of the molecular etiology of Ichthyosis. As the result was inconclusive, Whole Exome Sequencing (WES) was conducted. WES data analysis led to the identification of a mutation in the CAPN3 gene underlying limb-girdle muscular dystrophy type 2A (LGMD2A). Sanger sequencing confirmed the familial segregation of mutations. This work presents the first case worldwide of individual comorbidity of bathing suit ichthyosis and LGMD2A. The co-occurrence of two diseases should be systematically considered when establishing a diagnosis especially in consanguineous populations. WES is a powerful tool for molecular diagnosis in particular for revealing comorbidities and rectifying the diagnosis.

Absent meibomian glands and cone dystrophy in ADULT syndrome: identification by whole exome sequencing of pathogenic variants in two causal genes TP63 and CNGB3.

BACKGROUND: Ectrodactyly is a rare congenital limb malformation characterized by a deep median cleft of the hand and/or foot due to the absence of central rays. It could be isolated or depicts a part of diverse syndromic forms. Heterozygous pathogenic variants in the TP63 gene are responsible for at least four rare syndromic human disorders associated with ectrodactyly. Among them, ADULT (Acro-Dermato-Ungual-Lacrimal-Tooth) syndrome is characterized by ectodermal dysplasia, excessive freckling, nail dysplasia, and lacrimal duct obstruction, in addition to ectrodactyly and/or syndactyly. Ophthalmic findings are very common in TP63-related disorders, consisting mainly of lacrimal duct hypoplasia. Absent meibomian glands have also been well documented in EEC3 (Ectrodactyly Ectodermal dysplasia Cleft lip/palate) syndrome but not in ADULT syndrome. METHODS: We report a case of syndromic ectrodactyly consistent with ADULT syndrome, with an additional ophthalmic manifestation of agenesis of meibomian glands. The proband, as well as her elder sister, presented with congenital cone dystrophy.The molecular investigation was performed in the proband using Whole Exome Sequencing. Family segregation of the identified variants was confirmed by Sanger sequencing. RESULTS: Two clinically relevant variants were found in the proband: the novel de novo heterozygous missense c.931A > G (p.Ser311Gly) in the TP63 gene classified as pathogenic, and the homozygous nonsense pathogenic c.1810C > T (p.Arg604Ter) in the CNGB3 gene. The same homozygous CNGB3 variation was also found in the sister, explaining the cone dystrophy in both cases. CONCLUSIONS: Whole Exome Sequencing allowed dual molecular diagnoses: de novo TP63-related syndromic ectrodactyly and familial CNGB3-related congenital cone dystrophy.

Idiopathic Granulomatous Mastitis Associated with Erythema Nodosum in a Pregnant Woman.

A 32-year-old woman at 17 weeks' gestation presented with fever and a 1-week history of an acute nodular eruption involving her legs, along with bilateral ankle and knee pain. She also had had a recurrent right breast abscess for 2 months for which she had been treated with oral antibiotics and surgical drainage, but with slight improvement. Cultures of the abscess showed no bacteria or fungi. She had no history of tuberculosis, sarcoidosis, trauma to the breast, or a family history of breast pathology. Cutaneous examination revealed multiple, tender, erythematous, subcutaneous nodules on her legs (Figure 1) and an ill-defined tender mass involving the inferior quadrant of the right breast without nipple discharge or retraction. There was a scar with drainage on her right breast (Figure 2). There were no regional lymphadenopathies. Left breast and left axilla examination was unremarkable. Significant laboratory findings included an erythrocyte sedimentation rate of 54 mm/hour (normal levels [NL] < 20 mm/hour), an elevated C reactive protein at 148 mg/L (NL < 5 mg/L), and a high level of white blood cells averaging 15,000 elements/mm3 (NL < 10,000/mm3).