Three atypical/malignant onychopapillomas in a 52-case series with immunohistochemical study.

BACKGROUND: Onychopapilloma (OP) is a benign tumor of the nail. Haneke reported one case of malignant OP in 2021. No systematic immunohistochemistry study has been conducted on OP. The aim of our study was to identify possible malignant OP in our series of OP and to describe the immunohistochemical expression of p16, p53, and Ki67 in typical and atypical/malignant ones. METHODS: Ninety-one cases were available for pathological review. Immunohistochemical analysis could be performed on 52 cases. RESULTS: In 88 of 91 cases, the diagnosis of OP was confirmed. Three atypical/malignant cases were observed. No OP expressed p16. A normal p53 expression was observed in two thirds of the cases, an abnormal increased p53 expression in one third, including the three atypical cases. A normal Ki67 expression was observed in 84% of the cases, an abnormal Ki67 expression with focal heterogeneous expression in the suprabasal layers in 6% and in all suprabasal cell layers in 10%, including the three atypical cases. CONCLUSIONS: The diagnosis of atypical/malignant OP may be underestimated. The expression of Ki67 and p53 in these tumors differs from the expression observed in conventional OP. The absence of p16 expression confirms that human papillomavirus does not play a role in the etiopathogenesis of OP.

Elevated cutaneous expression of stem cell factor in chronic spontaneous urticaria: a prospective cohort study.

BACKGROUND: Tissue expression of endothelial cell (EC) markers of microcirculatory changes in CSU is poorly investigated. OBJECTIVE: to explore the expression of specific EC markers (stem cell factor (SCF), vascular endothelial growth factor (VEGF) and membrane attack complex (MAC)) in CSU-L and CSU-NL skin through immunohistochemistry (IHC) and in serum. METHODS: Lesional (L) and non-lesional (NL) skin biopsies from CSU patients and HCs were studied for the IHC expression of SCF, VEGF and MAC in CSU patients (n = 23) and healthy controls (HCs, n = 9). In this population, we also investigated blood levels of VEGF and SCF. Patients were also assessed for clinical characteristics, disease activity, and markers of autoimmune CSU (aiCSU). RESULTS: Epidermal SCF reactivity was significantly higher in CSU-L skin compared to HC skin (p=0.026). In the dermis, SCF immunoreactivity was seen particularly on endothelial, perivascular and epithelial cells. In CSU-L skin, mean perivascular SCF stainings were significantly more intense compared to HCs (p<0.001). Furthermore, CSU-NL skin also showed significantly higher SCF stainings on dermal perivascular cells compared to HCs (p<0.001). CSU patients had the highest SCF immunoreactivity scores in the epidermis and/or on dermal ECs. These patients did not have significantly higher SCF serum levels. CONCLUSION: This is the first study to show elevated cutaneous expression of SCF in chronic spontaneous urticaria. These findings underline the potential therapeutic possibilities of anti-KIT antibodies in CSU treatment.

Onychomatricomas: A 41-Case Series to Assess Surgical Outcome.

BACKGROUND: Onychomatricoma (OM) is a rare benign tumor of the nail matrix. Treatment is surgical, but data are currently limited. OBJECTIVE: To review all cases of OM operated in their department and to assess the link between the location on the nail plate, the thickness and width of the lesion, and the postoperative outcomes. MATERIALS AND METHODS: Records of 62 patients were retrieved from their department's database over a 25-year period (1998-2023). RESULTS: Of the 62 patients, 41 were eligible. In total, 58% of OM occupied a width of a quarter of the nail plate, 51% had a plate thinner than 3 mm, and 51% were laterally located. Of the 41 patients included, 29 had a tangential excision and 12 underwent lateral longitudinal excision. Among the tangential excision group, 71% had normal nail regrowth. Onychomatricoma thicker than 3 mm and involving the total nail plate width had a sequelae in 60% of cases. CONCLUSION: Tangential excision of onychomatricomas allows a normal nail regrowth in 71% of cases. The risk of sequelae increases for tumors thicker than 3 mm and involving the total nail plate width. Medial or lateral location seems to have no influence.

Chronic Spontaneous Urticaria in Belgium: Deciphering the Clinical Profile and Treatment of Patients Visiting an Urban City Immunology Department.

BACKGROUND: Chronic urticaria (CSU) is a chronic inflammatory mast cell-driven disorder of which reliable clinical data in Belgium are lacking. This study focusses on clinical characteristics of CSU patients presenting at an urban Immunology-Allergology department. METHODS: Outpatients with CSU were included from 2018 to 2021. Clinical characteristics, Dermatology Life Quality Index (DLQI) and Urticaria activity score (UAS7) were collected by thorough anamnesis and questionnaires. Furthermore, patients underwent provocational testing, an autologous serum skin test (ASST) and a blood analysis. RESULTS: The study included 49 CSU patients and 20 non-CSU subjects. CSU was distributed differently with age and sex, showing higher numbers in female patients below the age of 46 years. 67% of CSU patients had accompanying angioedema of which 9% were reported genital. CSU patients scored a mean 8/30 on their DLQI questionnaire. There was no significant difference in immunoglobulin E (IgE), C-reactive protein, and tryptase levels between CSU patients and controls. Oral glucocorticosteroids were prescribed in 23% of CSU patients during their disease course though only half of these patients had a severity grade 4 CSU. In 82% of the included CSU patients, Urticaria Control Test (UCT) scores were below 12. When we hypothetically considered low IgE levels and high IgG anti-thyroid peroxidase levels as differentiation marker for autoimmune (ai)CSU and non-aiCSU, we found that 4% of all included CSU patients could be considered aiCSU. CONCLUSION: Generally, the inner-city population displayed the same clinical characteristics, as previous cohorts from Northern Europe. The relatively high rate of CSU patients receiving oral glucocorticosteroid treatment for their disease though not always classified as severe, underlines the need to train doctors of various specialties in the treatment algorithms of CSU. Furthermore, by looking at potential autoimmune characteristics, our findings open perspectives on the identification of new routinely used clinical parameters for the detection of aiCSU, a relatively small immunological subtype of CSU.

Clinical and molecular diagnosis of genodermatoses: Review and perspectives.

Genodermatoses are a complex and heterogeneous group of genetic skin disorders characterized by variable expression and clinical and genetic heterogeneity, rendering their diagnosis challenging. DNA-based techniques, like whole-exome sequencing, can establish a diagnosis in 50% of cases. RNA-sequencing is emerging as an attractive tool that can obtain information regarding gene expression while integrating functional genomic data with regard to the interpretation of variants. This increases the diagnostic rate by an additional 10-15%. In the present review, we detail the clinical steps involved in the diagnosis of genodermatoses, as well as the current DNA-based technologies available to clinicians. Herein, the intention is to facilitate a better understanding of the possibilities and limitations of these diagnostic technologies. In addition, this review could guide dermatologists through new emerging techniques, such as RNA-sequencing and its applications to familiarizing them with future techniques. Currently, this multi-omics approach is likely the best strategy designed to promote the diagnosis of patients with genodermatoses and discover new skin disease genes that could result in novel targeted therapies.

Intralesional steroid injections for inflammatory nail dystrophies in the pediatric population.

Intralesional injections of triamcinolone acetonide are widely used to successfully treat several inflammatory nail conditions. This procedure is well described in adults, but less frequently reported in children and teenagers, being largely considered too invasive and fear-provoking for pediatric patients. Our report shows how this procedure is feasible and successful in children, even without a digital block. The step-by-step technique and tips to reduce pain should encourage clinicians to offer it as an alternative option to children with inflammatory nail disorders.

A clinicopathological description of COVID-19-induced chilblains (COVID-toes) correlated with a published literature review.

BACKGROUND: The abundance of publications of COVID-19-induced chilblains has resulted in a confusing situation. METHODS: This is a prospective single-institution study from 15 March to 13 May 2020. Thirty-two patients received PCR nasopharyngeal swabs. Of these, 28 patients had a thoracic CT-scan, 31 patients had blood and urine examinations, 24 patients had skin biopsies including immunohistochemical and direct immunofluorescence studies, and four patients had electron microscopy. RESULTS: COVID-19-induced chilblains are clinically and histopathologically identical to chilblains from other causes. Although intravascular thrombi are sometimes observed, no patient had a systemic coagulopathy or severe clinical course. The exhaustive clinical, radiological, and laboratory work-up in this study ruled-out other primary and secondary causes. Electron microscopy revealed rare, probable viral particles whose core and spikes measured from 120 to 133 nm within endothelium and eccrine glands in two cases. CONCLUSION: This study provides further clinicopathologic evidence of COVID-19-related chilblains. Negative PCR and antibody tests do not rule-out infection. Chilblains represent a good prognosis, occurring later in the disease course. No systemic coagulopathy was identified in any patient. Patients presenting with acral lesions should be isolated, and chilblains should be distinguished from thrombotic lesions (livedo racemosa, retiform purpura, or ischemic acral necrosis).

Distal phalangeal bone erosions observed by HR-pQCT in patients with psoriatic onycholysis.

OBJECTIVES: PsA prevalence among skin psoriasis is ∼30%. Nail psoriasis, especially onycholysis, is present in >70% of PsA and the risk of developing PsA is more than doubled in patients with nail involvement. We hypothesized that onycholysis may be associated with early bone erosions of the DIP joint without harbouring PsA symptoms. METHODS: We compared tendon thickness, assessed by US, and bone erosions, assessed by high-resolution peripheral quantitative CT, of the DIP joint in patients with psoriatic onycholysis without PsA (ONY) with those in patients with cutaneous psoriasis only (PSO). We used patients with PsA as reference (PsA group), and healthy age-matched controls (CTRL). Differences between groups were assessed by analysis of variance tests followed by post hoc analysis using the Scheffe method. RESULTS: Mean (s.e.m.) age of the 87 participants (61% males) was 45.2 (1.3) years. The mean extensor tendon thickness was significantly larger in ONY than in PSO patients. In the PsA group, 68% of patients exhibited erosions of three different shapes: V-, Omega- and U-shape. Association with erosions was greater in the ONY group than in the PSO group (frequency: 57 vs 14%; P < 0.001; mean number of erosions: 1.10 (0.35) vs 0.03 (0.03); P < 0.001). CONCLUSION: Onycholysis was associated with significant enthesopathy and bone erosions in our cohort. These data support the pathogenic role of enthesopathy in PsA. Onycholysis may be considered as a surrogate marker of severity in psoriasis. TRIAL REGISTRATION: ClinicalTrails.gov, https://clinicaltrials.gov, NCT02813720.

Markers for the involvement of endothelial cells and the coagulation system in chronic urticaria: A systematic review.

Chronic urticaria (CU) is a chronic inflammatory mast cell-driven disorder. Endothelial cells (ECs) contribute importantly to key features of CU. Several markers of EC (dys)function in CU have been reported, but have not yet been systematically reviewed. In this study, we systematically reviewed and categorized all published markers of EC functions in CU through a comprehensive search in Pubmed, The Cochrane Library, Web of Science, and SCOPUS using the following Mesh terms: CU AND pathogenesis AND (vasculopathy OR microangiopathy OR ECs OR marker). In total, 79 articles were selected and the identified biomarkers were categorized according to EC (dys)function in CU. The most frequent and consistently reported upregulated biomarkers in CU skin were adhesion molecules, TF, and P-selectin. The most frequently reported upregulated and reliable biomarkers in sera of CU patients were F1+2 for coagulation cascade involvement, D-dimers for fibrinolysis, and MMP-9 for vascular permeability. Emerging biomarkers described in the selected articles were endostatin, heat shock proteins, cleaved high molecular weight kininogen, and adipokines. This systematic review contributes to the pool of growing evidence for vascular involvement in CU where EC dysfunction is present in different aspects of cell survival, maintenance of vascular structure, and coagulation/fibrinolysis balance.

Direct examination, histopathology and fungal culture for the diagnosis of onychomycosis: A retrospective, comparative study on 2245 specimens.

BACKGROUND: Onychomycosis affects 5.5% of the general population and represents up to 50% of all nail diseases. Diagnosis and pathogen identification are essential in order to plan an adequate treatment. Many diagnostic techniques are available, and however, no solid data regarding comparison between different techniques over a large number of specimens are available to date. OBJECTIVES: To compare sensitivity and specificity of direct examination, histopathology and fungal culture in our referral mycology laboratory. METHODS: Nail specimens received at the cutaneous pathology and mycology laboratory of the University Hospital Saint-Pierre (Brussels, Belgium) between 1 January and 15 May 2018 were retrospectively analysed. All specimens were submitted to direct examination and culture. In cases of adequate specimen size, histopathology was performed. Fungal culture was considered the gold standard for diagnosis. RESULTS: A total of 2245 nail samples were included in the study. Onychomycosis was diagnosed in 1266 specimens. Sensitivity and positive predictive value were found to be higher for direct examination compared to histopathology, while sensitivity of direct examination was found to be lower. Combined approach with all the three techniques showed the highest rate of positivity, followed by the association of direct examination and histopathology. CONCLUSIONS: To our knowledge, this study included the largest number of nail specimens to date, allowing a comparison between direct examination, culture and histopathology. Direct examination showed to be the most performing technique in routine practice. Histopathology represents the most effective option in cases where both specimen size and laboratory resources are adequate. Our paper adds to the literature the 'real-life' experience of the mycology laboratory of a referral centre for nail diseases.

Isolated nail lichen planus: An expert consensus on treatment of the classical form.

Lichen planus is a benign inflammatory disorder of unknown etiology that may affect the skin, mucosae, scalp, and nails. When the nails are affected, it may lead to permanent destruction with severe functional and psychosocial consequences. Therefore, prompt diagnosis and early treatment are essential, even in mild cases. There are currently no guidelines for the management of nail lichen planus and the published literature on treatment is limited. The aim of this review is to provide practical management recommendations for the classical form of nail lichen planus, especially when restricted to the nails. Topical treatment has poor short-term efficacy and may cause long-term side effects. Instead, intralesional and intramuscular triamcinolone acetonide should be considered first-line therapies. Oral retinoids are second-line choices, and immunosuppressive agents may also be considered.

Acne fulminans induced by a low dose isotretinoin: case report and review of the literature.

Acne fulminans is a rare complication of classic acne. Less than 200 cases have been reported. It usually affects adolescent males with pre-existing acne vulgaris. It is characterized by an acute eruption of numerous and large inflammatory nodules, plaques, erosions, and ulcers covered by hemorrhagic crusts. The disorder may occur spontaneously or may be triggered by isotretinoin. We report a young boy who developed acne fulminans after isotretinoin therapy at a dose of 0.1mg/kg/day. A systematic literature review gathering previously reported cases on PubMed revealed that one similar case has been reported. Regarding therapeutic strategies, there are no randomized clinical trials to identify the best treatment for acne fulminans. Recommendations are based on case series and case reports. We share this case to raise awareness of the induction of acne fulminans by a very low dose of isotretinoin.

Recommendations for the definition, evaluation, and treatment of nail psoriasis in adult patients with no or mild skin psoriasis: A dermatologist and nail expert group consensus.

Nail involvement in psoriasis is common, and the severity of it does not always parallel the intensity of cutaneous disease. We created a consensus group, of which the aim was to provide practical recommendations for the treatment of nail psoriasis in patients without skin psoriasis or with mild skin lesions with no indication for a systemic treatment. This collaborative process was conducted by an international panel of dermatologists with special expertise in nail disorders, using formal consensus methods. During this process, the panel strived to establish an agreement regarding the definition of nail psoriasis, the severity of nail psoriasis, and treatment response. Treatment recommendations are provided regarding nail psoriasis severity and matrix or bed involvement. Few-nail disease was considered as nail psoriasis affecting ≤3 nails. In the case of matrix involvement only, intralesional steroid injections were considered the treatment of choice. Topical steroids alone or in combination with topical vitamin D analogues were suggested for nail psoriasis limited to the nail bed. For the systemic treatment of nail psoriasis acitretin, methotrexate, cyclosporine, small molecules, and biologics may be employed.

Treatment of Ingrowing Toenails With Phenol 88% or Trichloroacetic Acid 100%: A Comparative, Prospective, Randomized, Double-Blind Study.

BACKGROUND: Phenol is the gold standard for chemical matricectomy in ingrowing toenail. Recently, trichloroacetic acid (TCA) was used as cauterant. Both agents have high success rates but a postoperative healing time claimed to be faster for TCA rather than phenol. OBJECTIVE: Comparing the efficacy, the postoperative oozing time, the inflammatory reaction, and the postoperative pain. MATERIALS AND METHODS: Comparative, prospective, randomized, double-blind study. Eighty-four patients with 96 ingrowing toenails were randomized in 2 groups. Forty-six ingrowing toenails were treated with phenol 88% and 50 with TCA 100% within a 4-month period. Patients were observed 4 times for the presence of oozing and for the degree of inflammation. Patients assessed also oozing and pain on a scale basis during 34 days. RESULTS: Oozing was observed to be less with phenol treatment, as from the second week. Inflammation was also significantly inferior in the phenol group at Week 4. Patients evaluated the incidence of pain below 2/10 for both cauterants, while oozing was higher with TCA during 34 days. The overall success rates of both groups were similar with 100%. CONCLUSION: Phenol and TCA are both effective but TCA does not offer any advantage in terms of postoperative morbidity compared with phenol.