Diagnosis and Management of Longitudinal Erythronychia: A Clinical Review by an Expert Panel.

Longitudinal erythronychia (LE) is defined as a longitudinal red band of the nail(s) and is classified as localized (involvement of one nail) or polydactylous (involvement of more than one nail). The differential diagnosis is distinct for these classifications. The etiologies of localized longitudinal erythronychia (LLE) are most frequently benign subungual neoplasms, and less often malignancies. Polydactylous longitudinal erythronychia (PLE) is typically secondary to regional or systemic diseases, including lichen planus and Darier disease. LE is a common, but underrecognized clinical finding. Increased dermatologist awareness of the clinical characteristics and differential diagnosis for LE is necessary given the possibility for malignancy and associated systemic disease. In this clinical review, the clinical features, differential diagnosis, evaluation, and management of LE are described.

Clinical, onychoscopic, nail clipping, and histopathological findings of malignant onychopapilloma.

This report describes the clinical, onychoscopic, nail clipping, and histopathologic features of a malignant onychopapilloma. A 71-year-old male presented to our outpatient clinic for a stable, asymptomatic lesion on his left middle finger that had been present for 2 years. Prior nail clipping histopathology showed nail plate thinning with subungual abnormal onychocytes. Clinical examination revealed a 2-mm-wide streak of longitudinal xanthonychia extending to the proximal nail fold, with distal hyperkeratosis and onycholysis. Onychoscopy showed irregular longitudinal nail plate ridging with scattered punctate hemorrhagic foci. An excisional nail unit biopsy demonstrated cellular atypia of the nail bed epithelium, matrix metaplasia, longitudinal abnormal onychocytes, increased Ki-67 staining, and negative HPV immunoperoxidase staining, confirming the diagnosis of malignant onychopapilloma.

Prevalence of subungual melanoma in patients with cutaneous malignant melanoma: A systematic review and meta-analysis.

BACKGROUND: Subungual melanoma (SUM) is a rare type of cutaneous malignant melanoma (CMM) associated with poor prognosis, while data regarding its prevalence are scarce. OBJECTIVES: We sought to provide a comprehensive systematic review and meta-analysis of the prevalence rates of SUM among all types of CMM, considering certain demographic and clinical characteristics. METHODS: The MEDLINE electronic database was searched systematically to identify eligible studies providing prevalence rate estimates of SUM in patients with CMM. Included studies were further analysed to estimate the relative prevalences of SUM according to study design, study years, geographical region and sex distribution. RESULTS: Twenty-eight studies met the inclusion criteria. The overall SUM prevalence was 1.9% (95% CI [1.5%-2.3%]). The prevalence of SUM did not differ significantly between population- and hospital-based studies and remained stable over time. However, it was found to be significantly higher in Asians compared to patients of other geographical regions as well as in studies with more men than women compared to those with female preponderance (p < 0.001). CONCLUSIONS: In all, the overall SUM prevalence among all subtypes of CMM was estimated at 1.9%, without significant changes over time, and was found to exhibit significant variability between subgroups of different geographical regions.

A call for nail clipping histopathology to become an essential component of the routine evaluation of melanonychia: Benefitting patients as a triage and surgical planning maneuver.

We call on dermatologists and dermatopathologists to include nail clipping histopathology as an essential component of the routine evaluation of melanonychia. This manuscript demonstrates a case where an adult woman with broad melanonychia of the right thumbnail declined a nail matrix biopsy, but was amenable to a nail clipping.The nail clipping showed pigmentation, melanocyte remnants, and small cavities in the nail plate. These features have been published previously by our group as a clue to nail unit melanoma within nail clippings.This patient was rapidly triaged for nail matrix biopsy, which demonstrated nail unit melanoma in situ. Every patient with melanonychia can benefit from a nail clipping by examination of the location of the pigmentation within the nail plate for surgical planning, and if melanocyte remnants are detected, the nail clipping also serves as a rapid triage mechanism for nail matrix biopsy to evaluate for nail unit melanoma. Fontana-stained sections will highlight the pigmentation in the nail plate, and its location in the nail plate can easily be described by the dermatopathologist. Nail clippings performed in the setting of clinically apparent melanonychia may show helpful histopathologic findings of pigmented fungi, hemorrhage, external pigmentation, features of other pigmented nail unit tumors, as well as other entities. Nail clipping histopathology can provide extensive information in the evaluation of melanonychia with minimal discomfort for a patient, and little disruption to a physician's clinic flow. With this additional case of a nail unit melanoma diagnosed after initial concern found in a nail clipping, as well as other information in the literature, it is clear that melanocyte remnants found in nail clippings are reliable concerning features related to nail unit melanoma in adults. With knowledge of these histopathologic features in nail clippings and the significance of melanocyte remnants, the dermatopathologist can play a crucial role in the use of a nail clipping as a life-saving diagnostic maneuver. Accordingly, given the potential benefit to patients in this setting, as well as other uses of a nail clipping in the evaluation of melanonychia, we call on dermatologists and dermatopathologists to innovate the routine evaluation of melanonychia through the routine employment of nail clippings for histopathologic evaluation.

Clinicohistopathologic challenges and traps in the diagnosis of nail unit melanoma.

Melanoma of the nail apparatus is challenging to diagnose for both dermatologists and dermatopathologists. Misdiagnosis or delayed diagnosis of nail unit melanoma can have fatal consequences and legal ramifications. This review educates dermatopathologists on challenges and traps they should be aware of to avoid misdiagnosis of nail unit melanoma. We present illustrative difficult cases that introduce several themes regarding challenges in the diagnosis of nail unit melanoma: specimens with subtle histopathologic findings, challenges in immunoperoxidase interpretation, and how clinical knowledge and surgical procedural knowledge are mandatory to make the diagnosis. Dermatopathologists will be aware of when and how to suspect nail unit melanoma in unusual circumstances.

Pleomorphic acquired digital fibrokeratoma: A novel clinicopathologic entity.

A 26-year-old male presented with a 2-year history of a hyperkeratotic growth from the left index finger. Histopathology was consistent with an acquired digital fibrokeratoma with changes of a pleomorphic fibroma. Lesional cells were negative for CD34, Rb, and p53, and were positive for FXIIIa. We introduce the pleomorphic acquired digital fibrokeratoma as a novel clinicopathologic entity.

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.

Retrospective analysis of the histopathologic features of basal cell carcinomas in pediatric patients with basal cell nevus syndrome.

Basal cell nevus syndrome (BCNS) is an autosomal dominant condition caused most often by a loss-of-function mutation in the Patched-1 (PTCH1) gene. It is characterized by the development of varied benign and malignant tumors, including numerous cutaneous basal cell carcinomas (BCCs). The PTCH1 gene is integral in hair follicle development and loss of function mutation may lead to BCCs with an infundibulocystic histopathology in BCNS patients. Few studies have described the histopathological features of BCCs in BCNS. The recognition of these histopathologic features by dermatologists, dermatopathologists, and others caring for children will allow earlier and more effective identification of BCNS. We performed a retrospective analysis of 25 BCCs in 11 patients aged 5 to 19 years with BCNS and evaluated the histopathologic features on hematoxylin-eosin-stained sections. Our study found that 80% of BCCs in BCNS patients occurred on the head and neck with 64% of the specimens demonstrating infundibulocystic differentiation. Infundibulocystic differentiation is a common finding in BCCs found in BCNS. The finding of cutaneous neoplasms consistent with BCC with infundibulocystic differentiation in children is common in pediatric patients with BCNS and can be considered to be an early marker of the disorder, prompting further clinical investigation.

Shapiro xanthogranuloma: An essential diagnosis for dermatologists and dermatopathologists to recognize to avoid misdiagnosis of a hematopoietic malignancy in infants and neonates.

The Shapiro xanthogranuloma is a histopathologic form of xanthogranuloma that shows closely packed monomorphous cells, which can extend into the subcutaneous fat; it usually lacks routine diagnostic features of xanthogranuloma. Herein we describe two cases of Shapiro xanthogranuloma occurring in a neonate and in an infant, which were initially thought to be hematologic malignancies. One patient's presentation as a "blueberry muffin baby" added to the diagnostic confusion. Pediatric dermatologists, dermatologists, and dermatopathologists need to be aware of the Shapiro xanthogranuloma and its clinicopathologic features to avoid misdiagnosis of a hematopoietic malignancy in neonates and infants.

Subcutaneous fat necrosis of the newborn presenting as circular alopecia: a novel presentation.

Subcutaneous fat necrosis (SCFN) is an inflammatory disorder of the adipose tissue that commonly presents in neonates as tender subcutaneous nodules on the trunk and extremities with hypercalcemia as a potential complication. We report the case of a 3-month-old female who presented with circular alopecia of the scalp and was found to have histopathologically confirmed SCFN. Recognition of SCFN as a cause for alopecia in young infants may allow prompt screening for hypercalcemia and reduce the risk for associated morbidity and mortality.

Lichen striatus colocalized with a Spitz nevus.

A 7-year-old healthy girl presented with an 11-month history of an asymptomatic red, dome-shaped papule on her right medial elbow and 6-month history of linearly distributed, few millimeter, flesh-colored papules extending from and including the red papule. Histopathology demonstrated features of both a Spitz nevus and lichen striatus. The Spitz nevus was removed with a punch biopsy and the lichen striatus subsequently resolved. To our knowledge, co-localization of a Spitz nevus with lichen striatus has not been previously reported and highlights the potential association between the immunogenicity of Spitz nevi and the development of lichen striatus.

New-onset head and neck dermatitis in adolescent patients after dupilumab therapy for atopic dermatitis.

BACKGROUND/OBJECTIVES: Head and neck dermatitis after dupilumab therapy for atopic dermatitis has been frequently reported in adults and only rarely in adolescents. No cases detailing disease course and treatment response have previously been described in adolescents. METHODS/RESULTS: This case series presents five adolescent patients who developed new-onset or worsening head and neck dermatitis after dupilumab therapy for atopic dermatitis. All five patients improved after oral antifungal therapy. CONCLUSIONS: The clinical features, treatment response, and potential disease pathogenesis in pediatric patients are described. Adolescents with new-onset head and neck dermatitis after dupilumab therapy may clinically improve with antifungal therapy, suggesting that Malassezia species may be a contributing factor or antifungal therapy may be an effective antiinflammatory agent.

Bowel-associated dermatosis-arthritis syndrome in a child with very early onset inflammatory bowel disease.

A 6-year-old boy with severe very early-onset inflammatory bowel disease (VEO-IBD) was admitted for 1 week of high fevers, loose stools, joint pains, and myalgias. He subsequently developed a progressive, papular, and vesiculopustular eruption on his face with rapid spread to his trunk and extremities. Histopathology demonstrated dense dermal neutrophilic inflammation. Findings were consistent with bowel-associated dermatosis-arthritis syndrome (BADAS), which is rarely reported in children and requires further characterization.

Further delineation of the phenotypic spectrum of nevus comedonicus syndrome to include congenital pulmonary airway malformation of the lung and aneurysm.

Nevus comedonicus syndrome (NCS) is a rare epidermal nevus syndrome characterized by ocular, skeletal, and central nervous system anomalies. We present a 23-month-old boy with a history of a congenital pulmonary airway malformation (CPAM) of the lung and a congenital cataract who developed progressive linear and curvilinear plaques of dilated follicular openings with keratin plugs (comedones) on parts of his scalp, face, and body consistent with nevus comedonicus. MRI of the brain demonstrated an aneurysm of the right internal carotid artery. Genetic testing identified NEK9 c.1755_1757del (p.Thr586del) at mean allele frequency of 28% in the nevus comedonicus. This same mutation was present in the CPAM tissue. This is the first case of a CPAM in a patient with an epidermal nevus syndrome. This case expands the phenotype of nevus comedonicus syndrome to include CPAM and vascular anomalies.

Pediatric nail disorders: a review.

PURPOSE OF REVIEW: Nail disorders represent an uncommon subset of complaints seen in pediatric dermatology. There is a wide array of disorders that can affect the nail unit in children, including infectious, inflammatory, neoplastic, congenital, and traumatic processes. In order to enhance familiarity with pediatric nail conditions, we review the background and treatment of the more common entities seen in pediatric onychology, including onychomycosis, onychomadesis, nail psoriasis, trachyonychia, longitudinal melanonychia, onychophagia, and onychocryptosis. RECENT FINDINGS: Nail involvement in pediatric patients with psoriasis may indicate increased risk for both overall disease severity and the development psoriatic arthritis. In the evaluation of longitudinal melanonychia, the clinical findings that raise concern for subungual melanoma in adults are often found in benign nail unit nevi in children. In the systemic treatment of pediatric onychomycosis, new data raises the possibility that laboratory monitoring may be approached differently. In the approach to onychophagia, emerging pharmacotherapies include N-acetylcysteine. SUMMARY: Most nail disorders in pediatric patients have an overall favorable prognosis. However, nail abnormalities can lead to patient and parental anxiety, decreased quality of life, pain, and functional impairment. Clinicians should be aware of these more common diverse entities in order to identify them and apply state of the art management for these issues. Additionally, the reader will learn factors related to these nail disorders, which may require systemic work-up and/or specialist referral.

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.

The histopathological features of the nail plate in pachyonychia congenita.

BACKGROUND: Pachyonychia congenita (PC) is a rare autosomal dominant disorder of keratinization mediated by genetic mutations in KRT6A, KRT6B, KRT6C, KRT16, or KRT17. While nail dystrophy in PC has a significant impact on quality of life, the histopathological features of the nail plate in PC have not been previously reported. We report the histopathological features of nail plates provided by 19 patients with genetically confirmed PC. METHODS: Nineteen patients with genetically confirmed PC provided a total of 56 nail plates for histopathologic examination. The nail plates were examined for the presence of hyphae, yeast, bacteria, neutrophils, parakeratosis, plasma globules, and hemorrhage. Specimens with onychomycosis (three patients) were excluded from the analysis. RESULTS: No specific histopathological feature was identified in PC nails. Parakeratosis and plasma globules were the most prominent features in both clinically affected and unaffected PC nails. There was a significant association between clinical dystrophy of all 20 nails and KRT6A mutations, and a lack of dystrophy of all 20 nails in KRT6B mutations. CONCLUSIONS: Parakeratosis and plasma globules in the absence of other inflammatory disorders should raise PC in the histopathologic differential diagnosis. The presence of onychomycosis in a nail plate does not exclude a diagnosis of PC.

Verruciform xanthoma in a patient with recessive dystrophic epidermolysis bullosa: Case report and literature review.

Verruciform xanthoma (VX) is a rare finding thought to be caused by epidermal damage from trauma or inflammation and has been reported in a limited number of patients with recessive dystrophic epidermolysis bullosa (RDEB). Herein, we describe a 20-year-old woman with RDEB who developed a large, verrucous, pink plaque on the posterior thigh that was histologically proven to be a VX. We review cases of VX in patients with RDEB and summarize the clinical features, pathophysiology, and management principles.

Segmental congenital hemangiomas: Three cases of a rare entity.

Congenital hemangiomas (CHs) are unusual and diverse tumors distinguished from infantile hemangiomas by being largely developed at birth and glucose transporter (GLUT1)-negative. We describe three infants who presented in utero or at birth with segmentally distributed vascular tumors that were GLUT1-negative, had histology compatible with congenital hemangioma, and exhibited spontaneous clinical involution. One of the three patients had high-output cardiac failure and was found to have a mutation in GNAQ (c.626A>c, p.Gln209Pro); another had high-output cardiac failure, heterotaxy, and transient hematologic abnormalities and was found to have a mutation in GNA11 (c.626_627delinsCC, p.Gln209Pro). In addition to describing a novel segmental pattern of congenital hemangioma variant with genetic correlations, these cases illustrate the utility of targeted genetic testing to elucidate the exact mutation and thus classification of vascular tumors.

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

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