Polydactylous Squamous Cell Carcinoma of the Nail Unit: A Structured Review of the Literature.

Squamous cell carcinoma of the nail unit (SCCNU) is a rare neoplastic condition that involves multiple digits (polydactylous SCCNU) in only 3.9% of cases. Here, we report a case of polydactylous SCCNU and perform a comprehensive review of MEDLINE and Embase to collate 44 cases of polydactylous SCCNU reported to date. Polydactylous patients were younger on average (48 to 61-63 years) and had a longer diagnostic delay (44 vs 35.1 months) compared with reported monodactylous cases. Human papillomavirus (HPV) positivity was observed in 49% of cases, and the most common serotypes noted were 16 (25.8%), 73 (16.1%), 58 (9.7%), 18 (6.5%), and 33 (6.5%). Twenty percent of the cases were in immunosuppressed individuals who had a statistically significant lower age at diagnosis (39.33 years vs 51.12 years; P = .01) and diagnostic delay (2.50 months vs 132.46 months, P = .04). Patients with HPV positivity had a lower age at diagnosis (43.74 years vs 53.29 years, P = .04). Environmental exposures noted to be associated with polydactylous disease included X-rays, paint/solvents, soluble oils, and stagnant water. This comprehensive literature review serves to characterize polydactylous SCCNU and distinguish the differences in its characteristics to improve diagnosis and clinical recognition.

Tofacitinib for the Treatment of Nail Lesions and Palmoplantar Pustulosis in Synovitis, Acne, Pustulosis, Hyperostosis, and Osteitis Syndrome.

Importance: Nail involvement is common in synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome, which has a strong association with quality of life in patients with SAPHO. Tofacitinib is an oral Janus kinase inhibitor that has been previously shown to be effective for nail psoriasis. Objective: To assess the efficacy and safety of tofacitinib for the treatment of nail involvement in SAPHO syndrome. Interventions: Participants received tofacitinib, 5 mg, twice daily, for 12 weeks. Design, Setting, and Participants: This open-label, single-arm, prospective pilot study included 13 patients with SAPHO syndrome accompanied by nail lesions and active palmoplantar pustulosis who were recruited from Peking Union Medical College Hospital from September 2019 to December 2019. Follow-up was completed in March 2020. Analysis began March 2020. Main Outcomes and Measures: The primary end point was the percentage of the change from baseline in Nail Psoriasis Severity Index scores at week 12. Secondary end points included the percentage of the change from baseline in Palmoplantar Psoriasis Area and Severity Index scores, change from baseline in Visual Analogue Scale scores in global osteoarticular pain, Dermatology Life Quality Index scores, and inflammatory markers. Adverse events were recorded throughout the study. Results: Thirteen female Asian patients (means [SD] age, 39.7 [12.3] years) were included, all of whom completed the study. At week 12, significant improvements were observed in Nail Psoriasis Severity Index scores (median, -67% [interquartile range (IQR), -56% to -77%]; P < .001) and Palmoplantar Psoriasis Area and Severity Index scores (median, -71% [IQR, -58% to -78%]; P < .001). Significant improvement was also noted in Dermatology Life Quality Index scores (median, -12 [IQR, -8.5 to -15]; P < .001) at week 12. A significant decrease in Visual Analogue Scale scores in global osteoarticular pain was observed at week 8 (median, -4 [IQR, 0 to -5]; P = .02) but was not significant at week 12. Inflammatory marker levels were decreased, as indicated by erythrocyte sedimentation rate (median, -8 mm/h [IQR, -4 mm/h to -11 mm/h]; P < .001) and high-sensitivity C-reactive protein levels (median, -1.6 [IQR, -0.3 to -4.1]; P = .01). No severe adverse events were observed. Conclusions and Relevance: In this pilot study, tofacitinib yielded significant remission of nail lesions and palmoplantar psoriasis accompanied by an improvement in quality of life in patients with SAPHO syndrome. Additional follow-up studies to evaluate the long-term efficacy and safety of tofacitinib for nail involvement in SAPHO syndrome are warranted. Trial Registration: Chinese Clinical Trial Registry number: ChiCTR1900025941.

Nail Psoriasis Treatment: Insights into Current Progress and Future Trends.

Nail psoriasis is a chronic condition which causes pain and functional impairment; thus, it restricts the activities of daily living and worsens the quality of life. Different chemotherapeutic options are available for treating nail psoriasis such as systemic, intralesional, and topical therapies. However, current chemotherapy suffers from several limitations and to overcome them, new advancements are being made worldwide. Various reports have been published on current progress in the treatment of nail psoriasis such as clinical efficacy studies of novel antipsoriatic agents and novel formulation strategies for current chemotherapy. There are several novel nail formulations for the treatment of nail disorders, particularly onychomycosis, such as vesicular colloidal structure (liposomes, niosomes, transfersomes, ethosomes, etc.) and nonvesicular colloidal structures (nano-emulgel, nanocapsules, thermosensitive gel, etc.) These formulations can also prove beneficial for the treatment of nail psoriasis, and will be heavily explored in the near future. This review provides a brief introduction to the disease, its pathogenesis, and its treatment modalities. The review also throws light onto progress and future perspectives in nail psoriasis treatment.

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.

Nail manifestations in atopic dermatitis: a systematic review.

BACKGROUND: Nail involvement is not well-studied in atopic dermatitis but is believed to be more common than what is known. The spectrum of nail disorders that result from underlying atopic dermatitis (AD) is wide and has been reported in several studies, but there has been no systematic review so far to understand and quantify its prevalence. OBJECTIVE: To determine the prevalence and type of nail disorders seen in AD, either as a complication of the underlying condition or as a clue to its early diagnosis. METHODS: The authors performed a systematic review of English and non-English articles using MEDLINE, EMBASE, and Cochrane which reported the proportion of nail changes among AD patients. Only studies specifically looking at AD and its associated nail manifestations were included. Data were extracted and summarized descriptively. RESULTS: Twelve studies reported proportion of nail changes among AD patients. One study reported numbers in both adults and children cohorts, allowing 13 cohorts for final systematic review. CONCLUSIONS: Knowledge of the types and prevalence of nail changes in AD raises awareness among physicians managing AD.

Alopecia areata in Tunisia: epidemio-clinical aspects and comorbid conditions. A prospective study of 204 cases.

BACKGROUND: Alopecia areata (AA) is an autoimmune condition that usually presents as patchy, nonscarring hair loss. Autoimmune disorders and atopy are reported as comorbid conditions. We aimed to investigate the demographics, clinical characteristics, and associations of AA in Tunisian patients. METHODS: Demographic data, pattern of alopecia, age of onset, and associations were evaluated in 204 patients from January 2012 to June 2016. RESULTS: Two hundred and four cases of AA were seen. The male to female ratio was 0.68. The mean age at presentation was 23 years old. Positive family history was noticed in 22.1% of patients. Personal history of atopy was associated with AA in 18.1%. Associated autoimmune diseases were thyroid disorders (12.7%), vitiligo (1.5%), psoriasis (three cases), type 1 diabetes (two cases), autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) syndrome (two cases), lichen sclerosus atrophicus (one case), and pemphigus vulgaris (one case). Patchy AA was the most common manifestation (49.5%) followed by alopecia universalis (27.5%), alopecia ophiasis (12.7%), and alopecia totalis (10.3%). Nail changes consisting of pitting, trachyonychia, and longitudinal ridging were reported in 24.8%. AA patterns were more severe in females (P = 0.049). Severe forms showed more persistent disease duration (P = 0.005), earlier onset (P = 0.001), and more recurring episodes (P = 0.002) and were significantly associated with nail involvement (P < 0.001). CONCLUSIONS: Our study aimed to review epidemio-clinical characteristics and comorbid conditions of AA in Tunisian patients. More severe cases with a pejorative value of early-onset AA, long disease duration, and nail involvement were seen in our study.

Nail changes in autoimmune blistering disorders: A case-control study.

BACKGROUND: Pemphigus and pemphigoid disorders produce blistering cutaneous lesions. Earlier case reports state that nail involvement is uncommon in these autoimmune blistering disorders. AIMS AND OBJECTIVES: To study nail changes in autoimmune blistering disorders. METHODS: A case-control study was conducted where 40 cases and 40 controls were evaluated for nail changes. RESULTS: Nail changes were seen in 72.5% of cases and 17.5% of controls. The most common nail findings were paronychia and onychorrhexis. LIMITATIONS: Small sample size; short study duration; nail biopsy could not be done. CONCLUSION: Our findings indicate that the inflammatory nature of the blistering cutaneous disease is often reflected conspicuously in the nails.

Nail unit squamous cell carcinoma in people with immunosuppression.

BACKGROUND: Nail unit squamous cell carcinoma (NUSCC) is uncommon and diagnosis is often initially incorrect or delayed. Immunosuppression appears important in the clinical behaviour of NUSCCs. OBJECTIVES: To highlight the frequency and nature of immunosuppression in a case series of patients with NUSCC, and identify the distinguishing characteristics in this subgroup. MATERIALS AND METHODS: Clinical, photographic and histological details were reviewed for all patients with NUSCC, over a 16-year period in a university dermatology department. RESULTS: Forty-three patients were identified and seven (16%) were immunosuppressed. Patients with immunosuppression presented at a younger age (mean 52 vs. 63 years, P = 0.08) and sooner (mean 9 vs. 65 months, P < 0.001) than immunocompetent patients, and had a higher frequency of polydactylous disease [four of seven (57%) vs. two of 36 (6%), P < 0.001], relapse at the same site [two of seven (29%) vs. 0], and recurrent disease at other sites [four of seven (57%) vs. 0]. CONCLUSIONS: Immunosuppression plays a role in the development and clinical behaviour of NUSCCs. Clinicians should have a low threshold for early biopsy of nail dystrophies, particularly in those with immunosuppression. These patients are at higher risk of relapse and recurrent disease and therefore require prolonged follow-up.

Frequency, pattern, and extent of skin diseases in relation to CD4+ cell count among adults with human immunodeficiency virus infection or acquired immunodeficiency syndrome in Osogbo, southwestern Nigeria.

BACKGROUND: Skin diseases characterize all stages of human immunodeficiency virus (HIV) infection and acquired immunodeficiency syndrome (AIDS) and contribute significantly to associated morbidity and mortality. OBJECTIVES: The aim of this study was to document the prevalences, patterns, and extents (severity) of skin diseases and their relationships with immunologic status in HIV/AIDS patients. METHODS: A total of 140 HIV/AIDS patients in different stages of HIV infection and 140 controls were recruited. Skin diseases were documented and CD4+ cell counts determined in all subjects. Severity was assessed according to the body surface area affected (using the Wallace rule of nines and the rule of palm) for lesions that tended to be widespread. The number of digits involved was counted for lesions involving the nails. Intensity of pain was graded for specific conditions such as herpes zoster. Chi-squared statistics and Pearson correlations were determined. RESULTS: Mean±standard deviation age was 35.04±8.83 years in the patient group and 32.21±8.30 years in the control group. The prevalences and patterns of skin diseases in HIV/AIDS patients were similar to those reported in previous studies. Most commonly found dermatoses were oral candidiasis (n=28, 20.0%), pruritic papular eruption (n=27, 19.3%), xeroderma (n=23, 16.4%), dermatophytosis (n=22, 15.7%), and fluffy hair (n=19, 13.6%). The presence of specific skin lesions represented a better correlate with immunosuppression than cutaneous extents. However, the extents of viral warts and multiple blue­black nails correlated significantly with CD4+ cell count. The presence of a lighter hair color phenotype signifies a lower CD4+ cell count than a softer hair phenotype. CONCLUSIONS: The presence of specific skin lesions correlates more strongly with a low CD4+ cell count than does the extent of their distribution, except in cases of viral warts. The presence of and higher numbers of nails affected with blue­black nail hyperpigmentation suggest severe immunosuppression.

Superficial acral fibromyxoma: a clinicopathological and immunohistochemical analysis of 12 cases of a distinctive soft tissue tumor with a predilection for the fingers and toes.

AIM: Superficial acral fibromyxoma (SAFM) is a rare soft tissue tumor, recently delineated and documentated as a separate entity. We report 12 cases of SAFM observed in our department from June 2004 to June 2010 and highlight pathological features and differential diagnosis. METHODS: Radiographic examination of the affected digit was performed in all patients. All the tumors were surgically excised under local anesthesia. Follow-up was made every 6-8 months for a maximum period of five years. RESULTS: The patients consisted of 8 men and 4 women, age range 28-76 years (mean 51), presenting with a solitary mass or nodule located in the toes and fingers. Histologically the lesions were well circumscribed dermal nodules composed of stellate and spindle cells, arranged in a myxoid matrix. Very low grade atypia and a few mitotic figures were found in only one case. Neoplastic cells showed immunoreactivity for CD34 (12 patients). In contrast focally positive or negative staining was shown for the epithelial membrane antigen (EMA) and CD 99. Actin, S100 protein, HMB45 and cytokeratin were negative. In three cases marked hyperkeratosis and acanthosis of the epidermis was present. Pathological analysis confirmed the diagnosis of superficial acral fibromyxoma. No recurrences were observed even in a long term, 2-5 year follow-up. CONCLUSION: Complete surgical excision of the tumors and a careful follow-up is suggested, despite the benign course previously reported.

Nail involvement in autoimmune bullous disorders.

Autoimmune bullous disorders frequently cause nail abnormalities, particularly paronychia and onychomadesis. In pemphigus vulgaris (PV) nail abnormalities can even precede skin findings. Nail lesions often relapse just before generalized disease exacerbation or recurrence. Severe nail changes are often associated with extensive and severe disease. Fingernails are more commonly affected. A report in the literature associates hemorrhagic nail abnormalities with poor prognosis in patients with PV. Nail scarring and pterygium are a rare complication of bullous pemphigoid. Nail loss has been occasionally reported in epidermolysis bullosa acquisita.

Evaluation of nail disease in psoriatic arthritis by using a modified nail psoriasis severity score index.

BACKGROUND: The Classification of Psoriatic Arthritis Study Group published new criteria for classifying psoriatic arthritis (PsA) which included nail psoriasis. Our aim was to clarify the clinical importance of nail disease in PsA patients. METHODS: We investigated the types and severity of nail disease by using the modified nail psoriasis severity score index (mNAPSI) in 23 PsA patients and 23 patients with uncomplicated psoriasis. We analyzed the relationships of mNAPSI with nail fold psoriasis, psoriasis area and severity index score, swollen and/or tender joint counts, distal interphalangeal (DIP) joint disease, acute phase reactants and the score on the Japanese version of the standard health assessment questionnaire. RESULTS: The mNAPSI in 23 PsA patients was higher than that of controls (4.8 ± 5.3 vs. 2.3 ± 3.7, P < 0.05). The severity of fingernail disease in PsA patients was significantly associated with DIP joint disease (8.6 ± 5.9 vs. 3.1 ± 3.3, P < 0.05) and nail fold psoriasis (6.7 ± 5.2 vs. 3.5 ± 5.2, P < 0.05). There were no correlations between the mNAPSI and other systemic involvements. CONCLUSIONS: The nail involvement and prolonged nail bed psoriasis were common in PsA patients. Nail fold psoriasis and DIP joint arthritis were associated with nail involvement in PsA patients. Nail psoriasis would be related to the Koebner phenomenon and local inflammatory DIP joint arthritis in PsA patients, and we suggested that nail involvement in PsA was among the disorders indicative of distal phalanx enthesitis.

Nailing down the genetic and immunological basis for psoriatic disease.

Psoriatic disease encompassing skin, joint and nail involvement is largely viewed as autoimmune--a finding supported by data from animal models, the human leucocyte antigen (HLA)-Cw6 disease association in man, T-lymphocyte infiltration in lesional skin and the favourable skin response to T-cell-directed therapies. However, this immunopathogenetic model only applies to the skin, as recent studies failed to demonstrate a HLA-Cw6 association with the nails or joints. Furthermore, the nails and joints are intimately associated with inflammation at points of ligament or tendon insertion (i.e., enthesitis), so it is now appreciated that both of these sites also share a common microanatomical basis. Moreover, inflammation at insertion sites and nails does not appear to be associated with a particular antigenic territory but is quite diffuse in nature. This suggests that an aberrant response to tissue stressing of the integrated nail-joint apparatus, rather than autoimmunity, is driving the inflammatory process. Therefore, HLA-Cw6-associated type 1 psoriasis is more closely linked to autoimmunity, whereas nail and joint disease may be linked to tissue-specific factors, including tissue biomechanical stressing and microtrauma, that lead to activation of aberrant innate immune responses. These observations that stem from nail disease point toward a relative differential involvement of adaptive and innate immunity in the psoriatic disease spectrum and offer a fresh perspective on the pathophysiology of psoriatic disease and how it can be classified along the immunological disease continuum of self-directed inflammation.