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Pemphigus is a group of autoimmune mucocutaneous bullous disorders characterized by acantholysis resulting from autoantibodies targeting epithelial cell surface antigens. Studies reflect the presence of nail manifestations in some patients and suggest a potential correlation with clinical severity. This study examines the overall prevalence and characterizes the diverse manifestations of nail changes in pemphigus. We searched Cochrane, MEDLINE, EMBASE, and LILACS from 1990 to June 26, 2023 for studies reporting different nail changes in pemphigus patients. Data were collected and pooled to obtain proportions of the prevalence of nail changes in patients with pemphigus and subgroup analysis for pemphigus foliaceous and pemphigus vulgaris. The risk of bias was assessed with the Joanna Briggs Institute Checklist. Of 321 studies screened, 14 studies with 1,208 patients were included. Paronychia (n = 185) and Beau's lines (n = 104) were the most common nail changes identified. The pooled prevalence of nail disease in pemphigus patients was 0.389 (number of studies; [95% CI]: n = 9; [0.160-0.680], with high heterogeneity between studies (I 2  = 95.0%, P < 0.001). Subgroup analysis revealed the highest prevalence in pemphigus foliaceous at 0.342 (n = 3; [0.109-0.688]) and pemphigus vulgaris at 0.396 (n = 5; [0.114-0.769]). Nail changes exhibited varied temporal relationships with disease onset and flares, preceding, concurrent, or following these events. Correlation with disease severity was noted, although discrepancies between studies were reported. Nail changes in pemphigus, particularly pemphigus vulgaris and pemphigus foliaceous, may be underrecognized. Observations regarding temporal associations and potential correlations with disease severity highlight the diagnostic and prognostic implications of nail changes in pemphigus. The limitations of this study include study heterogeneity and possible bias. Further research to establish the correlation of the presence and severity of nail changes on the overall disease course would be helpful., (© 2024 the International Society of Dermatology.)

Competing Interests: Conflicts of interest None disclosed.

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.

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.

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., (Copyright © 2020 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

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., (© 2019 The International Society of Dermatology.)

Competing Interests: Competing interests The BMJ has judged that there are no disqualifying financial ties to commercial companies. The authors declare the following other interests: none. Further details of The BMJ policy on financial interests are here: https://www.bmj.com/about-bmj/resources-authors/forms-policies-and-checklists/declaration-competing-interests

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.

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., (© 2019 The International Society of Dermatology.)

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., Competing Interests: There are no conflicts of interest.

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., (© 2015 British Association of Dermatologists.)

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 blue–black 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 blue–black nail hyperpigmentation suggest severe immunosuppression.

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.

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., (Copyright © 2011 Elsevier Inc. All rights reserved.)

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., (© 2010 The International Society of Dermatology.)

Objectives: To evaluate the use of grey/distal banded nails as an indicator of advanced immunosuppression, and thus eligibility for ART, in resource poor settings., Methods: We tested whether grey/distal banded nails and/or oral pigmentation could be used to identify patients with low CD4 cell counts at two cut-offs: <200 and <350 cells/microl in ART naive adults., Results: Four hundred and three nail and oral cavities were photographed and assessed. Grey/distal banded nails and/or oral pigmentation were significantly associated with a CD4 cell count <200 cells/microl (P < 0.001), with a sensitivity of 66%, a specificity of 50% and a negative predictive value of 77%. However, there was no association when a CD4 cell count cut-off of <350 cells/microl was used. Inter-observer agreement (k 0.46) was fair/moderate., Conclusions: While grey/distal banded nails and/or oral pigmentation are associated with low CD4 counts, the sensitivity and kappa score are too low for this method to be recommended as a tool to guide ART initiation; large number of individuals eligible for ART would be missed.

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., (Copyright (c) 2010 S. Karger AG, Basel.)

The traditional model for psoriasis and psoriatic arthritis (PsA) is that autoimmunity directed against a common skin and joint autoantigen leads to chronic autoreactive T cell driven inflammation. However, recent imaging, histological and genetic studies have challenged this view, especially with respect to joint and nail disease, and provide a broader insight into the pathogenesis of PsA and associated nail involvement. Clinically unrecognized enthesitis (inflammation at tendon and ligament attachments) is commonly seen in early PsA at all sites of the disease. Specifically, enthesitis is associated with adjacent osteitis or bone and synovial inflammation. Even in normal joints, normal insertions are associated with microdamage and inflammatory change, strongly suggesting that local tissue specific, or what has been described as autoinflammatory factors, may dictate disease expression. Distal interphalangeal (DIP) joint disease in PsA is associated with diffuse inflammation that envelops the nail root and adjacent bone. In fact, the nail is intimately linked to entheses, with the extension tendon of the DIP joint sending fibres from bone that envelop the nail root in an interdigitating fashion. Furthermore, the joint collateral ligament enthesis has fibres that merge with the lateral borders of the nail. Other anchorage mechanisms include fibres that directly tether the nail plate to the underlying periosteum, which itself is closely anchored to the extension tendon. The frequent microdamage and tissue repair at normal enthesis attachment sites in healthy joints has resulted in a proposed new model of PsA pathogenesis embracing the concept of autoinflammation, whereby tissue specific factors, including microtrauma, lead to regional innate immune activation and persistent inflammation, as an alternative to primary immunopathology driven by T and B cell abnormalities. Unlike the classical autoimmune diseases, which may attack a completely normal organ, autoimmunity in psoriatic disease is likely to involve tissues where there is intrinsic dysregulation of the target tissues. These tissue specific factors related to the enthesis appear to be key to the phenotypic expression of diseases hitherto regarded as autoimmune. The pathogenesis of PsA, nail disease and to a lesser extent psoriasis therefore appear to have an autoinflammatory (innate immune driven) rather than autoimmune basis. Taken together, these findings are important for better understanding PsA, nail disease and psoriasis, and for conceptualizing the immunopathogenic basis of these diseases and further exploring the role of enthesitis in their pathophysiology.

Purpose of Review: Both psoriasis and psoriatic arthritis (PsA), and by implication psoriatic nail disease, have been considered as autoimmune disorders. This was based on the assumption that T-cell-directed responses against common skin and synovial antigens led to shared immunopathological mechanisms at these different sites, which was indirectly supported by the human leucocyte antigen-Cw6 disease association. This study draws on recent microanatomical and genetic studies of PsA, psoriasis and psoriatic-associated nail disease to show how the prevailing autoimmunity concepts for psoriatic disease need to be redrawn, especially in the case of joint and nail disease., Recent Findings: Recent microanatomical studies confirm that normal tendon and ligament insertion points to bone (entheses), the key territory for the inflammatory reaction associated with PsA, being subject to microdamage that strongly points to a role for microtrauma in the joints, which is reminiscent of Koebner responses in the skin. Furthermore, the nail is functionally integrated with entheses associated with the distal phalanx that provides anchorage to the skin and joint. Although type 1 psoriasis is strongly linked to the human leucocyte antigen-Cw6, recent genetic studies have suggested that both joint and nail disease do not share this association., Summary: These microanatomical and genetic insights have important implications for a better understanding of PsA and nail disease and for an improved understanding of the psoriatic disease spectrum.

Lichen planus (LP) is an inflammatory dermatitis of idiopathic origin that can involve the skin, mucous membranes, hair and nails. Histologically, LP is characterized by compact orthokeratosis, wedge-shaped hypergranulosis, irregular acanthosis, damage to the basal cell layer and a band-like inflammatory infiltrate in the upper dermis. Lymphocytes are the predominant cells making up the infiltrate, along with a few macrophages, eosinophils and plasma cells. In addition, melanophages are often found in the upper dermis adjacent to the damaged basal cells.(1) We describe a patient with a lesion of the toenail clinically and histopathologically consistent with LP, but with a band-like inflammatory infiltrate composed primarily of plasma cells. Previously, only three other cases of LP with plasma cell predominant infiltrate have been reported, none of which involved the nail matrix., (Copyright Blackwell Munksgaard 2008.)

Background: Yellow nail syndrome (YNS) is a rare, often underdiagnosed condition of unknown origin. The clinical features of the syndrome include yellow nails, chronic sinusitis, bronchiectasis, pleural effusion, and lymphoedema. Despite the frequent occurrence of upper and lower respiratory tract infections in patients with YNS, comprehensive analysis of their humoral immunity has not been previously reported., Objective: To present the case of a patient with YNS whose recurrent upper and lower respiratory tract infections may have been caused by an underlying selective antibody deficiency that manifests as impaired IgG antibody response to polysaccharide antigens., Methods: The patient underwent cultures of purulent sputum for Streptococcus pneumoniae and Haemophilus influenzae, bronchial washings for H. influenzae, and nail scrapings for fungi. Her serum levels of IgG, IgA, IgM, IgG subclasses, and serum titers of IgG antitetanus toxoid, anti-H. influenzae, and anti-S. pneumoniae antibodies were measured., Results: Cultures of purulent sputum were positive on multiple occasions for S. pneumoniae and H. influenzae and bronchial washings were positive for H. influenzae. Nail scrapings were consistently negative for fungi. She had no reductions in serum levels of IgG, IgA, IgM, or IgG subclasses and had normal serum titers of IgG antitetanus toxoid antibodies. However, she demonstrated impaired IgG antibody responses following immunization with Pneumovax and an H. influenza B vaccine., Conclusions: This case report describes the first comprehensive analysis of humoral immune function in a patient with YNS. The finding of a selective antibody deficiency in our patient provides a potential explanation for the occurrence of respiratory infections in YNS. Accordingly, we recommend that functional antibody determinations and quantitative serum immunoglobulins be evaluated in patients diagnosed as having this unusual, enigmatic syndrome.

Background: Solitary sclerotic fibroma (SF) presents as a well circumscribed dermal nodule, composed of sparse spindle cells with alternating wavy collagen fibers arranged in a storiform pattern. The histogenesis and nature of this histologically distinct lesion are uncertain. Whether this peculiar tumor represents a true hamartoma or a degenerating end of various fibrous lesions such as pleomorphic fibroma (PF), dermatofibroma, or angiofibroma is still controversial. High proliferating index of spindle cells in SF argues against the possibility of being a degenerating end product of another lesion., Methods: We studied morphological features and immunoprofile of eight SFs, in comparison with four PFs, one collagenized dermatofibroma, two angiofibromas, and two periungual fibromas. Immunostains for CD34, CD31, O13 (CD99), Factor XIIIa, S-100, CD68 (KP-1), and MIB-1 were carried out using a labeled streptavidin-biotin method with DAKO-automated immunostainer. Paraffin blocks of two SFs were reprocessed for electron microscopic studies. Clinical data of all patients with SF were also reviewed., Results: Spindle cells and pleomorphic cells in SF and PF showed diffuse immunoreactivity for CD34 and O13 but were negative for CD31, S-100, and CD68. Spindle cells in one dermatofibroma and one angiofibroma were positive for Factor XIIIa. Proliferating index (MIB-1) was very low in all cases of SF, contradicting some previous reports., Conclusions: SF is a fibrotic lesion with cells positive for CD34 and O13. It shares a common immunoprofile with PF but is distinct from dermatofibroma and other common spindle cell lesions of skin. O13 expression in SF has not been previously described.

Primary antibody deficiencies are rare diseases, which require early treatment with intravenous immunoglobulins to prevent fatal infections. The cell mediated immunity in patients with those immunodeficiencies remains unimpaired and usually they do not develop fungal infections. The aim of the study was to determine the susceptibility to fungal infections of nails in children with X-linked agammaglobulinaemia (XLA) and common variable immunodeficiency (CVID). Nail plate fragments collected from five patients with XLA and five with CVID were experimentally infected with a Candida albicans and Trichophyton mentagrophytes strains. The same procedures were carried out with the nails from a control group of 10 healthy volunteers. The intensity of the infection was evaluated on the basis of hyphae ingrown into the nail fragments. The main finding of the study was the increased susceptibility of antibody deficient patients to experimental nail infection with C. albicans and T. mentagrophytes.

Background: Involvement of the nail unit in pemphigus vulgaris (PV) is thought to be rare., Objectives: To determine the frequency of nail changes among patients with PV., Methods: Nail changes were recorded in patients with PV and were analysed retrospectively. Biopsies were taken from the nail bed and nail matrix for histological and immunofluorescence observations. Microscopic (potassium hydroxide) examination and fungal culture were performed., Results: Nail changes were present in 30 of 64 (47%) patients with PV. Sixteen patients had onychomycosis and 14 had nail changes due to PV. These included onychomadesis, discoloration, deformity, onychorrhexis, onycholysis, subungual haemorrhage, subungual hyperkeratosis and paronychia. Onychomycosis affected fingernails and toenails, but changes due to PV occurred only in fingernails, most commonly on the thumb and index finger. No connection was found between the patient's occupation and nail involvement, and there was no correlation with the severity or duration of PV. In a control group of 64 patients of similar sex and age, only two had non-specific fingernail changes., Conclusions: Nail changes in PV may be more frequent than previously thought.

The human equivalent form of the severe combined congenital immunodeficiency of the nude/SCID mouse has been recently described in 2 siblings originating from a small community in southern Italy. Similar to the mouse, the human phenotype is characterized by a profound T cell ontogenetic defect associated with congenital alopecia and nail dystrophy. The disease is related in either mice and humans to molecular alterations of the gene encoding a forkhead/winged helix transcription factor, which is selectively expressed in thymic epithelia. Remarkably, due to the selectivity of the tissue expressivity of the gene responsible for the syndrome, this is the first example of SCID not primarily related to an hematopoietic cell abnormality, but rather to thymic aplasia. The opportunity to study immunological reconstitution in the absence of a functioning thymus following a bone marrow transplantation from a related HLA-identical sibling gave us insight into the role of the thymus in in vivo T cell ontogeny and maintenance of T cell functionality. This model led us to address a few general issues that may have clinical implications.

HLA-B27 is highly linked with a group of human diseases called spondyloarthropathies (SpA). Many of these disorders begin after an infection with an enterobacteria. The symptoms seen in patients with spondyloarthropathies are inflammatory pain in the spine and asymmetrical arthritis of lower limbs. Additional symptoms related to SpA include inflammation in the eyes, bowel, and skin. The autoantigen(s) in SpA are not known. Proteins such as collagen and proteoglycans have been thought to be potent autoantigens in arthritidis including B27-associated human diseases. Type II collagen is a common denominator among eyes and joints, affected tissues in B27-linked diseases. Moreover, a few reports indicated CII specific T cells and antibodies in patients with spondyloarthropathies. We and others have previously described development of spontaneous arthritis and nail disease in HLA-B27 transgenic animals. To determine whether CII may be a target antigen in the B27-linked diseases, B27 + m beta 2 m% (HLA-B27) transgenic mice lacking mouse beta 2m with and without human beta 2m) mice were immunized with type II collagen inside the barrier facility. Male HLA-B27 transgenic mice developed collagen-induced arthritis compared to transgene negative littermates or female counterparts. There was no difference in the incidence of arthritis in HLA-B27 transgenic mice with and without human beta 2m. Our data suggest that beta 2m free heavy chain of HLA-B27 may present soluble antigens such as type II collagen to trigger specific T cells contributing in the development of arthritis. Our data also suggest that CII may be a potential target antigen in the cartilage during the disease process.

Although association of HLA-B27 with human spondyloarthropathies has been known for several years, its role in disease pathogenesis is not understood. Recently, a few investigators have proposed that presentation of B27-derived peptides by MHC class II molecules may be the underlying mechanism. HLA-B27 transgenic rat and mouse models have provided a new tool for understanding the exact role of B27 in disease pathogenesis. HLA-B27 mice lacking endogenous beta2-microglobulin (B27+ beta2m(o)) develop disease after they are transferred from the barrier facility to the conventional colony. This model was utilized to test the hypothesis that B27-derived peptide presented by MHC class II molecules is the cause of the disease. The MHC class II knockout gene, A beta(o), was bred into our B27+ beta2m(o) mice, and disease manifestation was monitored. These mice develop spontaneous disease, demonstrating that MHC class II molecules do not play a major role in B27-related disease. Thus, the disease is not manifested by presentation of B27-derived peptides by class II molecules, since these mice are devoid of H2-A and H2-E molecules. Furthermore, in vivo treatment with mAb against the heavy chain of B27 reduced the incidence of disease in B27+ beta2m(o) mice. Our results clearly demonstrate that B27 heavy chains are directly involved in the disease process.

We report on two sisters affected by congenital alopecia, nail dystrophy, and a severe T-cell immunodeficiency, presumably inherited as an autosomal-recessive disorder. The T-cell defect was characterized by severe functional impairment, as shown by the lack of proliferative response and upregulation of activation markers following mitogen stimulation. The functional abnormality occurred in spite of the presence of phenotypically mature of the defect. This is the first observation reported on an ectodermal disorder, characterized by alopecia and nail dystrophy, observed at birth, in association with a primary immunodeficiency. The hypothesis that these two events may be casually related is discussed.

The prevalence of dermatophyte infection was assessed in 100 patients with well-controlled insulin-dependent diabetes, and in a control group of 100 non-diabetics matched for age, sex, occupation and sporting activity. Immediate and delayed responses to intradermal testing with Trichophyton antigen were recorded in both groups. The overall infection rate (skin and nails) was 19% in diabetics and 17% in controls. There was a higher infection rate in the skin of diabetics (17%) than in controls (8%), but this was not significant. Nail infection was seen in 12% of diabetics and in 11% of controls. Intradermal testing with Trichophyton antigen gave a higher proportion of both immediate and delayed positive results in diabetics. However, more control patients showed only an immediate positive response or only a delayed one. There was no evidence of an increased infection rate in those with immediate positive responses or of diminished infection rates in those with delayed positive responses, and no correlation with oral Candida infection. These findings applied equally to diabetics and controls.

Background: Induction of delayed-type hypersensitivity has recently been introduced for resistant viral warts. The method is not painful and less destructive than most other modalities., Objective: We assessed the efficacy of topical diphencyprone (diphenylcyclopropenone) treatment for recalcitrant warts., Methods: From September 1988 to June 1995, 134 patients with periungual and/or palmoplantar warts were entered into the study. Eight weekly applications were delivered., Results: The scheduled treatment course and follow-up were completed by 111 patients. There were 49 complete and 18 partial remissions. The rate of positive responders (60%) compares with the results published by other authors., Conclusion: Diphencyprone is an effective treatment for resistant warts, especially in palmoplantar and periungual locations.

In a recent study we detected marked differences in the antigenic profile of acral lentiginous melanoma (ALM) and nodular melanoma lesions. Furthermore, we showed that the human high molecular weight melanoma-associated antigen (HMW-MAA) is expressed with a significantly higher frequency in metastatic than in primary ALM lesions. Because of the potential role of HMW-MAA in the metastatic process of melanoma cells, in the present investigation we tested whether HMW-MAA represents a useful prognostic marker in ALM. Primary ALM lesions removed from 32 patients were stained with anti-HMW-MAA monoclonal antibody (mAb) in an immunoperoxidase reaction. The results were correlated with the expression of other markers defined by mAb, with clinical parameters of the disease, and with histopathological characteristics of the lesions. Only 9 of the 32 primary ALM lesions tested were stained by anti-HMW-MAA mAb. Expression of HMW-MAA was the only variable associated with patients' survival and disease-free survival. Both were significantly shorter in patients with HMW-MAA expression in their primary lesions. These results suggest that HMW-MAA may represent a novel prognostic marker in ALM, since phenotyping of primary ALM lesions with anti-HMW-MAA mAb may provide information about the prognosis of the disease which cannot be obtained with known prognostic parameters.

Forty of 1095 patients (3.65%) with alopecia areata had severe nail changes that fulfilled the clinical criteria for the diagnosis of trachyonychia. Twelve of these patients had a nail biopsy. A mild to moderately dense lymphocytic infiltrate associated with exocytosis and spongiosis was detected in the proximal nailfold, nail matrix, nail bed, and hyponychium of 11 patients. One patient showed the pathologic changes of lichen planus; lichen planus of the skin developed 6 months after the nail biopsy. Immunohistochemical characterization on paraffin-embedded sections showed that the inflammatory infiltrate consisted of peripheral T lymphocytes. Immunophenotyping on frozen sections was performed in four cases. The results revealed a T4/T8 ratio of 2:1 and the presence of Langerhans cells in the nail matrix. Our results show that trachyonychia is an uncommon nail manifestation of alopecia areata. Distinctive pathologic features of mild to moderately dense lymphocytic infiltrate associated with exocytosis and spongiosis characterize trachyonychia as well as the other nail abnormalities caused by alopecia areata. The clinical association of trachyonychia with alopecia areata does not exclude that the nail abnormality can be due to other diseases such as lichen planus.

A 4-year-old girl with pachyonychia congenita was followed from birth. During childhood, slow progression of the nail hypertrophy was seen because she was not willing to have the nails ground or cut. After grinding of her nails under general anesthesia, the child has had acceptable nail thickness, and continued regular grinding without anesthesia. The child had recurrent oral and cutaneous candidiasis. Investigations showed a weakly positive response to Candida albicans in the lymphocyte transformation test, and absence of a delayed hypersensitivity skin test response to Candida. The secondary infection due to Candida seemed to prevail because of an immune defect.

The toe-nail dust produced in chiropodial practice causes allergic hypersensitivity and Trichophyton rubrum is the most common fungal cause of nail dystrophy. Use of drills and burrs to reduce the thickness of hyperkeratotic nails generates dust and chiropodists develop precipitins to T. rubrum. A survey into the prevalence of these antibodies in 11.2% of state-registered chiropodists is described and 14% of the profession estimated to have antibodies to T. rubrum. In response to a questionnaire 49% stated that toe-nail dust troubled them; complaints of nasal and eye symptoms were 72 and 41% respectively. In 384 chiropodists ventilatory function was tested with a vitalograph. Restrictive lung disease appears to be more common in chiropodists than other sedentary workers.

Diseases in which involvement of the nails may be helpful in the diagnosis of dermatologic disease elsewhere include psoriasis, lichen planus, Darier's disease, alopecia areata and totalis, keratotic scabies, scleroderma, and lupus erythematosus and dermatomyositis. Dermatologic diseases in which involvement of the nail commonly occurs but is relatively nonspecific and not diagnostic include dermatitis, lichen striatus, parakeratosis pustulosa, pityriasis rubra pilaris, acrokeratosis paraneoplastica, pemphigus vulgaris, epidermolysis bullosa, porokeratosis of Mibelli, and acanthosis nigricans. These entities are described and treatments summarized as appropriate.