Onychoscopic characteristics of Trichophyton rubrum and Trichophyton interdigitalis fungal infections: A multicentric study.

BACKGROUND: Trichophyton rubrum and Trichophyton mentagrophytes variant interdigitalis are the most frequent etiologic agents of onychomycosis. Diagnosis of certainty requires mycological examination, which often results unfeasible. OBJECTIVES: The aim of our study is to describe pathogen specific dermoscopic features, allowing a differential diagnosis without the need for cultural examination, in order to prescribe the most appropriate treatment anyway. PATIENTS AND METHODS: We conducted an observational retrospective study on 54 patients with a culture proven diagnosis of distal subungual onychomycosis of the toenail, caused by Trichophyton rubrum or Trichophyton mentagrophytes variant interdigitalis. Using a videodermatoscope we collected data on nail colour (white, yellow, orange, brown, dark) and on dermoscopic patterns (aurora, spikes, jagged, ruin, linear edge, dots, striae). RESULTS: Fifty-four patients, with a total of 72 nails, were eligible for this study. Analysing the association between discoloration of the nail plate and type of infection (T. rubrum or T. interdigitalis), no correlation turned out to be statistically significant. Instead, significant associations between spikes and T. rubrum infection and striae and infection from T. interdigitalis were identified. Finally, a 100% specificity was identified for white colour and ruin pattern for T. rubrum infection, and brown colour, jagged border and aurora pattern for T. interdigitalis. CONCLUSIONS: Trying to find relationships between specific pathogens and dermoscopic patterns, we found out an association between spikes and striae and T. rubrum and T. interdigitalis respectively. Further larger studies are however necessary to evaluate our preliminary findings.

Diagnosis and surgical treatment of benign nail unit tumors.

Little is known about benign non-melanocytic nail tumors, probably due to their low pathogenicity. They are commonly misdiagnosed as inflammatory or infective diseases. They have various features, depending on the type of tumor and its location in the nail apparatus. The typical sign of a tumor is the presence of a mass and/or secondary nail changes from damaged nail structures. In particular, if a single digit is affected by a dystrophic sign or a symptom is reported without any explanation, the presence of a tumor should always be ruled out. Dermatoscopy helps to enhance visualization of the condition and in many cases supports the diagnosis. It may also assist in identifying the right place to biopsy, but it never replaces surgery. Most common non-melanocytic nail tumors are analyzed in this paper, including glomus tumor, exostosis, myxoid pseudocyst, acquired fibrokeratoma, onychopapilloma, onychomatricoma, superficial acral fibromyxoma and subungual keratoacanthoma. The aim of our study is to review the main clinical and dermatoscopic characteristics of the most common benign non-melanocytic nail tumors, to correlate them with the histopathology and to advise practitioners of the best surgical management.

Mutational landscape in squamous cell carcinoma of the nail unit.

Squamous cell carcinoma (SCC) is the most common malignancy of the nail unit. Pathogenetic mechanisms are yet to be determined, and a deeper molecular characterization of this disease is still necessary. The aim was to obtain a molecular characterization of NU SCC samples using an NGS approach to identify the genetic drivers involved in this tumor. The presence of HPV infection was also assessed. Furthermore, the mutational status was correlated with specific clinical-pathological features for a better insight into the carcinogenesis of this uncommon tumor. We analysed twenty paraffin-embedded nail unit SCC samples from patients diagnosed with primary SCC of the nail unit by next genome sequencing. In the 20 tested samples, the neoplastic cells enrichment ranged from 10% to 50% (mean value: 25.7%). In 14/20 cases (70.0%), at least one mutation was detected; whereas in the other six cases (30.0%), no alterations were observed ('wild-type/WT cases'). Overall, a total of 23 mutations were identified in the 20 specimens. TP53 was the most mutated gene (6/20 cases, 30.0%), while cKit, GNAS, EGFR, DICER1 and CTNNB1 were observed in one sample each (5.0%). No clinical-pathological parameters (age, sex, depth of invasion-DOI, histological subtype, grading and HPV) were significantly associated with the mutational status. The nail unit SCC mutational landscape appeared to be heterogeneous, favouring the hypothesis of a complex pathogenesis and an interaction of multiple elements, including HPV infections. This wealth of information undoubtedly improves our understanding of SCC biology.

Clinical and onychoscopic features of histopathologically proven onychopapillomas and literature update.

BACKGROUND: Onychopapilloma is a benign tumor of the distal nail matrix and proximal nail bed with heterogeneous clinical presentations. It poses a diagnostic challenge because it could mimic subungual malignancies and inflammatory conditions. Clinical, onychoscopic, and histopathological clues play critical roles in diagnosis. METHODS: We performed a retrospective chart review of onychopapilloma cases collected over 10 years, and characterized the clinical, onychoscopic, and histopathological features of onychopapilloma at an academic institution. RESULTS: We obtained 17 biopsy-confirmed cases of onychopapilloma. Among our cases, we found manifestation of onychopapilloma as longitudinal erythronychia, longitudinal leukonychia, yellow-brown chromonychia, and longitudinal melanonychia. Long longitudinal or short splinter hemorrhages may be present. Distal fissuring with V-shaped notch, subungual keratotic mass, and onycholysis are other discernable features. Histopathological features include papillomatosis, epidermal hyperplasia, acanthosis of the distal nail bed, premature keratinization, matrix metaplasia, hyperkeratosis, and splinter hemorrhages; histopathological signs of malignancy were not observed in any of our cases. CONCLUSIONS: Onychopapilloma has polymorphic clinical and morphological features. Onychoscopic and histopathological studies are important to help exclude malignant mimickers. Consider onychopapilloma in the differential diagnoses of a monodactylous longitudinal streak in the nail, especially on the left thumb of an adult female.

Treatment of retronychia: A systematic review and suggested treatment algorithm.

Retronychia is an inflammatory disorder typical of the great toes characterized by arrested nail growth, ingrowth of the nail plate into the proximal nail fold and paronychia. There is no standardized treatment for retronychia, and its management should be weighed based on the severity stage, treatment modality, and clinical outcome. In this paper, a systematic review of the literature was performed to assess all published data regarding the treatment of retronychia. A total of 231 patients from 24 studies were included in the analysis. Conservative management was adopted in mild-intermediate forms, consisting of medical (topical or intralesional high-potency corticosteroids) and podiatric treatment (taping, clipping back the onycholytic plate, orthosis), leading to a global cure rate of 41.2%, with no reported side effects. Non-conservative management, that is, chemical or surgical avulsion of the nail plate, proved resolutive in 71.2% of cases. Surgical avulsion of the nail plate produced the highest cure rate (78.2%), but was burdened by 9.6% of long-term sequelae, mainly nail dystrophies. A decision-making algorithm was designed to give clinicians treatment indications based on the severity stage of retronychia, treatment invasiveness, and possible clinical outcomes.

Management of malignant cutaneous wounds in oncologic patients.

PURPOSE: Neoplastic wounds may develop as a result of primary tumor growth in the skin, due to metastasis, or due to skin invasion by tumors emerging from deeper levels. Malignant wounds may present as a crater-like ulcer, or as raised nodules with a cauliflower-like appearance. They are associated with malodor, necrosis, pain, bleeding, and secondary infection. The aim of our study is to better characterize fungating wounds and their management. METHODS: We retrospectively reviewed the database of the Wound Care Unit of the University of Bologna in order to identify individuals affected by neoplastic wound, between January 2019 and February 2021. RESULTS: We identified 9 females and 2 males with a mean age of 63 years; all were referred by the Oncology Unit. Management differed depending on the characteristics of the patients and the ulcers. Complete healing of the wound, following the parallel complete remission of the lymphoproliferative neoplasia, was observed in one individual. Among the others, one died because of breast cancer, while cutaneous lesions in 2 individuals deteriorated after 1 year of follow-up. Remission/relapse of the ulcer following the treatment course administered for the lymphoma were observed in one patient. CONCLUSIONS: Treatment of malignant fungating wounds is challenging. Considering the neoplastic nature of the wounds, complete healing or improvement cannot be expected with the application of classically prescribed dressing for wounds. A mostly palliative treatment, focusing on maintaining the patient's quality of life, is a reasonable choice.

BRAF V600K vs. BRAF V600E: a comparison of clinical and dermoscopic characteristics and response to immunotherapies and targeted therapies.

BACKGROUND: A number of mutations related to malignant melanoma (MM) have been identified, and of the mutated genes, BRAF has been found to be altered in > 50% of cases. Most of these have been BRAF V600E mutations, whereas the incidence of BRAF V600K may vary from 10% to 30%. Little is known about the clinical prognostic correlations of BRAF V600K MMs. We evaluated the clinical and dermoscopic features, incidence, therapy response and outcomes in the medium to long term. AIM: To compare the clinical and dermoscopic characteristics, the response to systemic therapies and the prognosis among MMs with BRAF V600E and BRAF V600K mutations. METHODS: We retrieved the data of patients tested in our centre for MM from 2012 to 2015, including clinical features, dermoscopic pictures, clinical history and tumour mutations. Only patients with BRAF V600E and BRAF V600K mutations were included. Any MMs positive for BRAF V600K mutation were collected, and the number of V600K cases and their features were used to extract the same number of patients with BRAF V600E from our database using a matching method. The clinical and dermoscopic presentation, therapy response and disease progression of the two groups were then evaluated. RESULTS: In total, 132 cases of BRAF V600E-mutated MMs were identified, and then randomized with a propensity-score method to match the 10 retrieved cases of BRAF V600K mutation. Both groups had a nodular appearance to the tumours and an advanced disease stage, and no significant differences in dermoscopic features were highlighted. During the follow-up period, four patients with BRAF V600K died of disease-specific causes. Moreover, we found a higher frequency of metastasis, a faster disease progression and more rapid mortality in patients with BRAF V600K. CONCLUSION: Despite the small size of this study, the results show similar clinical and dermoscopic characteristics between V600E and V600K mutations, but compared with BRAF V600E MMs, BRAF V600K MMs seem to be less responsive to therapy and have a worse prognosis.

A pilot study of intralesional methotrexate injections versus triamcinolone acetonide in patients affected by nail matrix psoriasis.

Nail disorders in general are difficult to treat and often frustrating, and this is also the case with nail psoriasis, especially when it is limited to the nails, and not affecting joints. The quality of life of patients with nail psoriasis is negatively affected, owing to the chronic course of the disease and frequent relapses. The purpose of this study was to compare treatment response and maintenance of response during follow-up of 12 patients with nail matrix psoriasis limited to a few nails, who were treated with intralesional injections of either methotrexate (MTX) 25 mg/mL or triamcinolone acetonide 10 mg/mL. Patients were treated every 6 weeks for 24 weeks and followed up for 6 months. Photographic documentation and assessment by Nail Psoriasis Severity Index were performed during each treatment session and at each follow-up visit. At the end of the four treatment sessions, all patients had improvement of their disease, which continued during follow-up, especially for the MTX-treated group.

Therapeutic approach with squaric acid dibutylester for steroid resistant-alopecia areata incognita: A pilot study of a single center.

Topical immunotherapy is widely used in the treatment of alopecia areata (AA). Alopecia areata incognita (AAI) is a relatively common disorder, predominantly affecting females, characterized by widespread hair thinning in the absence of typical alopecic patches. AAI can have a chronic relapsing course and in some cases can be resistant to current standard treatments. Topical immunotherapy has been used in the management of AA with encouraging results, but to date there are no literature studies reporting the efficacy of topical immunotherapy with squaric acid dibutylester (SADBE) in AAI. The aim of our study is to evaluate the efficacy and tolerance of topical immunotherapy with SADBE in AAI not responding to conventional steroid therapy. A total of 12 patients were enrolled in our Hair Disease Outpatient Service, with a proved histological diagnosis of AAI, and resistant to classical steroid therapy. Each patient underwent global photography, pull test, and trichoscopy at beginning and during the follow-ups. The efficacy of topical immunotherapy with SADBE was assessed by evaluating the changes of clinical and trichoscopic signs. Complete regrowth was achieved in 66.7% of cases (8/12), three patients remained unchanged on clinical evaluation but showed subclinical improvement on trichoscopy, whereas one patient progressed and worsened both on clinical and trichoscopic examination. All patients reported scalp diffuse mild erythema and itching the day after the application of SADBE, which were well tolerated. Three patients developed reactive cervical lymphoadenomegaly. No other side effects were observed. Topical immunotherapy with SADBE is widely used in the management of patchy AA and can be considered an effective alternative in resistant AAI, providing visible clinical and trichoscopic improvement in the majority of cases. Further studies are warranted to confirm and validate our findings.

Digital Myxoid Cysts: Correlation of Initial and Long-Term Response to Steroid Injections.

BACKGROUND: Digital mucous cysts (DMCs) are benign myxoid pseudocysts that develop on the distal interphalangeal joint's lateral or dorsal aspects. Management consists either of a surgical approach, conservative therapy, or simple follow-up. OBJECTIVE: To correlate the initial and long-term response with clinical and ultrasound parameters in DMCs treated with intralesional steroids as first-line therapy. METHODS: A single-center prospective open-label study recruited 15 patients affected by DMCs, who had been treated with a cycle of up to 3 steroid injections at a 6 to 9 week time interval. RESULTS: At the first follow-up visit, 53.3% of patients were cleared of DMCs, achieving a complete response, whereas 46.7% experienced a >30% decrease in their DMC volume, and were considered partial responders. After 1 year of follow-up, the cure rate decreased to 40%, and the recrudescence rate was 27.3%. Clinical and sonographic characteristics that positively correlated with a maintained complete response at follow-up were as follows: young age, absence of osteophytes, low volume, complete clearance at T1, and short disease duration (p < .05). CONCLUSION: Intralesional steroid therapy is an easy approach for DMC, with minimal side effects; identifying predictive hallmarks is useful to offer a straightforward surgical treatment to patients who have nonresponder characteristics.

Dermatophytic melanonychia: A case series of an increasing disease.

BACKGROUND: Melanonychia refers to brown-black colour pigmentation due to melanin or not-melanin deposition in the nail plate. Onychoscopy allows to distinguish if the pigmentation is due by melanin or not. The main causes of non-melanic pigmentation are subungual haematoma and pigmented onychomycosis. Fungal melanonychia (FM) is rare and may present as diffuse or longitudinal pigmentation. Differential diagnosis includes melanic activation, such as ethnic-type nail pigmentation or frictional melanonychia, but also versus melanic proliferation, such as nevus or nail melanoma. Fungal melanonychia can be due to a colonisation by fungi with black variant or by melanin activation due to inflammation of fungal invasion. OBJECTIVES: The aim of paper is to increase clinical and dermoscopic knowledge of this increasingly frequent disease. METHODS: In this retrospective observational study, twenty patients with dermatophytic melanonychia were collected, with available clinical and dermoscopic pictures. The diagnosis of dermatophytic melanonychia was made based on clinical manifestation and mycological examination. KOH smear was performed in all cases. For each patient, clinical data included: age, gender, type of melanonychia and involved fingers. RESULTS: This study aimed to show increased incidence of dermatophytic melanonychia and its correct management. In addition, we reviewed our collected cases and described the clinical and dermoscopic features of dermatophytic melanonychia. CONCLUSIONS: The results of this study showed that physicians should keep in mind the diagnosis of this increasing disease, and that it cannot be performed relying only on clinical grounds. We would like to highlight the importance of tools as KOH examination, culture and dermoscopy.

Short anagen syndrome: A case series and algorithm for diagnosis.

BACKGROUND: The short anagen syndrome (SAS) is a rare idiopathic pediatric disorder characterized by the short duration of the anagen phase. SAS mainly affects Caucasian children. Parents complain of their child's inability to grow long hair. Topical minoxidil may be an effective treatment for SAS; however, a slow spontaneous improvement is typical. OBJECTIVE: Our aim was to collect data on out cases of SAS and create an algorithm to facilitate diagnosis of SAS. METHODS: A retrospective review of 25 patients with SAS was performed within the Dermatology Department of the University of Bologna. We collected data regarding symptoms, pull test, hair card test, trichoscopy, trichogram, treatments, including biotin and minoxidil, and clinical outcome. RESULTS: Characteristic findings included parental reporting that the hair had not required a haircut, hair card test showing hairs with conical-shaped tips, and hair shafts of different diameters, with more 10%-20% of hair shafts less than 60 µm thick on trichoscopy. Trichogram revealed an increased percentage of telogen hair with normal hair shafts and tapering ends. The mean anagen-to-telogen ratio was 66:34 (normal ratio 90:10). CONCLUSION: We developed an algorithm to facilitate the diagnosis of this rare hair disease using clinical examination and invasive and non-invasive testing to differentiate SAS from other forms of pediatric alopecia. In conclusion, the collected data of the therapy showed that biotin alone or in combination with topical minoxidil is an effective treatment for SAS.

Tinea corporis incognito due to Microsporum Gypseum: Report of eight cases in children.

Microsporum gypseum is a geophilic saprophyte for which soil is the natural habitat. Tinea corporis caused by Microsporum gypseum is rare and usually occurs after direct contact with the soil or healthy carrier animals. We present a case series of eight children with tinea corporis caused by M gypseum, with unusual clinic presentations mimicking dermatitis.

Diffuse variants of scalp lichen planopilaris: Clinical, trichoscopic, and histopathologic features of 40 patients.

BACKGROUND: Fibrosing alopecia in a pattern distribution and cicatricial pattern hair loss are poorly recognized diffuse variants of lichen planopilaris (LPP). OBJECTIVES: The medical features of 40 patients affected by a diffuse hair thinning associated with a long-lasting history of pruritus and erythema of the scalp and a histopathologic diagnosis of LPP were reviewed. METHODS: Clinical data, results of trichoscopy and histopathology, response to treatment, and follow-up were analyzed. RESULTS: There were 18 patients diagnosed with fibrosing alopecia in pattern distribution and 2 patients with cicatricial pattern hair loss. A new variant of diffuse LPP, named "lichen planopilaris diffuse pattern," was described in 20 individuals. LIMITATIONS: Low number of cases due to rarity of the diseases. CONCLUSION: In patients complaining of a long-lasting history of scalp erythema, itching/dysesthesia, and diffuse hair thinning, it is advisable to consider diffuse variants of LPP.

Intralesional steroid treatment for the intermediate stage of retronychia: A pilot study.

Retronychia describes the proximal ingrowing of the nail plate. In the early stage, topical steroids are the gold standard therapy, while in the late stage surgical treatment is mandatory. We identified an intermediate severity stage of retronychia, where the topical treatment alone is ineffective and surgery is avoidable. Intralesional steroids turn the best treatment in these patients. A pilot study consisting of a 3-month treatment period and 9-month follow-up time was designed to evaluate the treatment outcome to intralesional steroid injections in patients affected by the intermediate-stage of toenail retronychia. The complete recovery of retronychia-associated nail abnormalities was observed in 27/28 recruited patients at the end of the treatment phase. Paronychia, nail plate discoloration, proximal nail fold (PNF) elevation, and discharge were reduced (P < .01) after one steroid administration, while nail regrowth became significant after two sessions. No significant difference in terms of clinical outcome was found, while pain VAS score and intra-operative pain evaluated with Wong-Baker faces scale were higher in the female group (P < .01). Limitation Lack of control group of patients. Despite its temporary effect, the intralesional triamcinolone injection is an effective, cheap, and safe treatment especially for the intermediate stage of retronychia.

Severe de-novo palmoplantar and nail psoriasis complicating Nivolumab treatment for metastatic melanoma.

Nivolumab, a fully human IgG4 immune checkpoint modulator, binds to the programmed cell death 1 (PD-1) receptor on T cells and blocks their inhibition. Thus, it increases the anticancer host immune response by allowing T cells to attack tumor cells. Although anti-PD-1 immunotherapy is typically well accepted, deregulation of immune tolerance caused by nivolumab may determine immune-related adverse events, among which skin toxicities represent the most common. We report a case of severe new-onset palmoplantar and nail psoriasis after receiving nivolumab treatment for metastatic melanoma.

Cutaneous adverse-events in patients treated with Ibrutinib.

Ibrutinib is a Burton tyrosine kinase inhibitor (BTKi) approved for the treatment of several hematologic malignancies. Analyze skin adverse events (SAE). All the patients treated with Ibrutinib featuring cutaneous adverse events were selected. Twenty five patients were retrieved with a median interval between Ibrutinib start and SAE time of onset of 120 days. Most common SAE observed involved hairs and nails. Eczematous reaction and leucocytoclastic vasculitis were also detected. One patient had a long-history Ibrutinib treatment and experienced numerous cutaneous adverse events. Infective disease such as superficial mycosis and impetigo were rarely present in our series. Despite the development of cutaneous SAE, all the patients continued their concomitant drugs without the onset of any further SAE. Our data suggest Ibrutinib-associated rash should be distinguished in early and late events and a careful dermatologic management of patients should be scheduled.

Ultrasound features of the subungual glomus tumor and squamous cell carcinomas.

BACKGROUND: Nail tumors often pose a significant challenge for the clinician, as they are burdened by a high delay in diagnosis and paucity of clinical signs in the early stage. In most cases, the onset of pain or nail plate dystrophy leads to imaging investigations such as plain radiography, magnetic resonance imaging, and ultrasonography (US) when surgery is pending. MATERIAL AND METHODS: A 2-year monocentric study evaluated the histologically confirmed cases of subungual glomus tumor (GT) and squamous cell carcinoma (SCC) with a pre-surgical US assessment, and reviewed their sonography features. A total of 7 digital GTs and 6 SCCs of the nail were collected. RESULTS: GT and SCC are easily distinguishable on US. Compared to SCC, GT was positively associated with an ovoid shape, well-defined borders, bone cup-scalloping without cortical erosion, and a rich intralesional vascular pattern (P < 0.05). Vice versa, SCC was significantly correlated with irregular shape, ill-circumscribed margins, an infiltrative growth pattern with peripheral hypoechoic foci, posterior acoustic shadow, cortical erosion, and a highly vascular multipolar peripheral pattern (P < 0.05). CONCLUSION: The rapid assessment of GT and SCC sonographic features may contribute to reduce diagnostic delay, expedite management, and decrease the risk of surgical relapse.

Clinical evidences of urea at high concentration on skin and annexes.

The antiproliferative, keratolytic, moisturizing and emollient properties of urea are already known. Clinical evidences of urea at high concentration indicate its important role in the presence of hyperkeratosis that, if severe or localized in specific body areas, may cause discomfort to the patient and may interfere with absorption of topical drugs, delaying response to treatment. Other important uses of urea at high concentration are on the scalp and on nail plate. The keratolytic effect of urea is well-tolerated and virtually free from side effects. Compliance with topical therapy is directly related to the aesthetic and sensory acceptability of a topical agent that may considerably vary in odour, spreadability and post-application residue.

Oral and nail pigmentations: a useful parallelism for the clinician.

Oral (OP) and nail (NP) pigmentations may occur simultaneously in physiological or pathological conditions, and may be a sign of underlying syndromic conditions that necessitate further investigation and treatment. Interestingly, the nail unit and oral cavity show a clinical parallelism that may help the clinician to conduct a correct examination and reach a prompt diagnosis. Both OP and NP can manifest clinically with focal or diffuse involvement and are due to external factors (exogenous pigmentation, drug-induced pigmentation) or endogenous factors (racial pigmentation, post-inflammatory pigmentation, nevi, genetic conditions and other disorders). The most concerning differential diagnosis is melanoma. Here we report the pathogenetic basis of OP and NP, together with the description of similar clinical features. To the best of our knowledge this is the first paper to summarize and describe the causes of pigmentation of both the oral cavity and the nail unit.