Maryanne M. Senna

The deep penetrating nevus

The deep penetrating nevus (DPN), also known as the plexiform spindle cell nevus, is a pigmented lesion that commonly arises on the head and neck in the first few decades of life. Histopathologically, the DPN is wedge-shaped and contains melanocytes that exhibit deep infiltration into the dermis. Given these features, DPN may clinically and histopathologically mimic malignant melanoma, sparking confusion about the appropriate evaluation and management of these lesions. The goal of this review is to summarize the clinical and histopathological features of DPN and to discuss diagnostic and treatment strategies for dermatologists.

A double-blind, placebo-controlled, phase-II clinical trial to evaluate oral simvastatin as a treatment for vitiligo

To theEditor:Vitiligo is anautoimmunedisease caused by autoreactive CD8 T lymphocytes that target melanocytes, and interferon-induced CXCL10 plays an important role. Simvastatin inhibits interferonsignaling by blocking activation of STAT1 and prevented and reversed disease in our mouse model. A case report described a patient with vitiligo who repigmentedwith simvastatin.We conducted a small, randomized, double-blind, placebo-controlled, phase II clinical trial to test simvastatin as a treatment for vitiligo. After obtaining informed consent, we enrolled men ages 18 to 64 years with vitiligo affecting 3% to 50% of their body surface area (BSA). We excluded patients with a segmental presentation; those already taking a 3-hydroxy-3-methylglutarylcoenzyme A reductase inhibitor; those with existing thyroid disease; and women, based on their increased risk of simvastatin-induced myopathy. This study was approved by our institutional review board (Clinicaltrials.gov identifier number: NCT01517893). Fifteen patients were randomized to either 40 mg of simvastatin daily for the first month and 80 mg for the remaining 5 months of the study period, or placebo. Topicals were discontinued for at least 2 weeks, oral immunomodulators for 4 weeks, and

A Practical Approach to the Diagnosis and Management of Hair Loss in Children and Adolescents

Hair loss or alopecia is a common and distressing clinical complaint in the primary care setting and can arise from heterogeneous etiologies. In the pediatric population, hair loss often presents with patterns that are different from that of their adult counterparts. Given the psychosocial complications that may arise from pediatric alopecia, prompt diagnosis and management is particularly important. Common causes of alopecia in children and adolescents include alopecia areata, tinea capitis, androgenetic alopecia, traction alopecia, trichotillomania, hair cycle disturbances, and congenital alopecia conditions. Diagnostic tools for hair loss in children include a detailed history, physical examination with a focused evaluation of the child’s hair and scalp, fungal screens, hair pull and tug test, and if possible, light microscopy and/or trichoscopy. Management of alopecia requires a holistic approach including psychosocial support because treatments are only available for some hair loss conditions, and even the available treatments are not always effective. This review outlines the clinical presentations, presents a diagnostic algorithm, and discusses management of these various hair loss disorders.

Limited Cutaneous Pseudovasculitis A Mild Variant of Cholesterol Emboli Syndrome

An 86-year-old woman was evaluated for painful hand nodules 3 days after a transcatheter aortic valve replacement. Each nodule arose as a discrete, painful skin-colored lesion that became larger and purpuric over the ensuing days (Figure 1). The patient denied any fevers, new arthralgia, cough, hemoptysis, hematuria, vision or speech changes, and weakness. Her medical history was notable for coronary and peripheral artery disease and severe aortic stenosis. She had no history of vasculitis or other autoimmunity. A transesophageal echocardiogram after the transcatheter aortic valve replacement revealed nonmobile aortic atheromas. Subsequent imaging studies were negative for both intramural and valvular thrombi, although atheromas in the ascending thoracic and abdominal aorta were seen. Her renal function remained within normal limits, and no peripheral eosinophilia or hypocomplementemia was noted. Her erythrocyte sedimentation rate and C-reactive protein levels were elevated, and she tested positive for anti-neutrophil cytoplasm antibodies (ANCAs) with perinuclear staining and myeloperoxidase antibodies. Biopsy …

Lipofibromatosis-like neural tumor: Case report of a unique infantile presentation

A 14-month-old boy presented with a slow-growing, asymptomatic back plaque, which was biopsied and found to have S100 positivity, sparse CD34 staining, and no significant mitotic activity, nuclear pleomorphism, or necrosis; genetic workup found LMNA-NTRK1 gene fusion, overall consistent with lipofibromatosis-like neural tumor (LPF-NT). LPF-NT is rare, with 14 cases previously reported, and our patient is the first report of this diagnosis in infancy. This case report and literature review includes comparison of similar diagnoses including lipofibromatosis, low-grade malignant peripheral nerve sheath tumor, infantile fibrosarcoma, and dermatofibrosarcoma protuberans and serves to aid detection of LPF-NT presenting in pediatric patients by highlighting similarities and differences that should prompt consideration. LPF-NT shows locally aggressive behavior only and should not be confused with conditions that have potential for distant spread. However, case reports of metastasizing LMNA-NTRK1 tumors draw into question whether growths with this gene fusion exist on a spectrum of disease severity. Our patient was treated with wide local excision and has developed no complications or evidence of recurrence with 6 months of follow-up time.

Immune Privilege Collapse and Alopecia Development: Is Stress a Factor?

Hair is a defining mammalian feature that serves as a hallmark of human communication. Given the critical significance of hair in social, religious, and political contexts, it is important to understand factors that play a role in hair loss disorders. The hair follicle is an immune privileged site, and mounting evidence suggests that the collapse of immune privilege contributes to the pathogenesis of autoimmune hair loss disorders, including alopecia areata and lichen planopilaris. This review comprehensively appraises the current literature to shed light on mechanisms for immune privilege collapse, and examines the role of neurogenic stress in triggering this process.

Long-standing pili torti in 2 patients with chronic graft-vs-host disease

cGVHD: chronic graft-vs-host disease HSCT: hematopoietic stem cell transplant INTRODUCTION Pili torti is a term that originates from Latin (pili meaning hair, torti meaning twisted) used to describe the irregularly flattened and twisted appearance of hair shafts on microscopic hair mount evaluation. Clinically, affected patients have fragile, coarse, and sparse hair. The 1808 rotation along the hair shaft axis is thought to be caused by perifollicular fibrosis and abnormalities of the inner root sheath, with subsequent irregular formation of the hair shaft. The characteristic narrow and numerous twists distinguish pili torti from other types of hair shaft disorders. Congenital pili torti has been associated with a number of syndromes, including Bj€ ornstad syndrome, Menkes syndrome, and others. Bj€ ornstad syndrome is known to be caused by a missense mutation in the BCS1L gene on chromosome 2q34-36. BCS1L encodes an ATPase that has a central role in the proper functioning of the electron transport chain. In Bj€ ornstad syndrome, BSC1L mutations cause variable degrees of pili torti and sensorineural hearing loss, shown to be due to disrupted mitochondrial respirasome assembly and increased production of reactive oxygen species. Reports of acquired pili torti are few and have been associated with the use of oral retinoids and erlotinib and, in some patients, cicatricial alopecia. In these cases, however, the pili torti is localized, and medication-induced cases tend to resolve after discontinuation of the offending agent. Herein we describe 2 women with chronic graft-vs-host disease (cGVHD) with long-standing, diffuse alopecia and pili torti.

Longstanding alopecia and nail dystrophy are associated with more severe overall chronic graft-versus-host disease in adults

Chronic graft-versus-host disease (cGVHD) causes significant morbidity and mortality for recipients of allogeneic hematopoietic stem cell transplants (HSCT) [1, 2]. The multisystem disease is prevalent in an estimated 80% of patients who receive HSCT and most commonly affects the skin, ranging from nonsclerotic epidermal involvement to deep sclerotic disease [3, 4]. The NIH Global Severity of cGVHD uses clinical assessment, laboratory findings, and patient reported symptoms to calculate the overall cGVHD severity score (mild, moderate, or severe). Although “skin” is one of eight organ systems included, grading of hair and nail involvement is not specifically required [4]. Although cGVHD-related alopecia and nail dystrophy have been documented in limited case reports, their overall prevalence in adults has not been well described [5]. Cutaneous involvement is thought to predict a poorer overall cGVHD prognosis [3], and patients with adnexal involvement have been shown to be less responsive to standard treatments [6]. The hair follicle and nail bed are immune privileged sites with lower-MHC class II expression of antigen presenting cells [7, 8]. Such mechanisms suppress T-cell activation and antigen recognition and should presumably reduce the probability of cGVHD in these areas [3, 7, 9]. Therefore, it may be reasoned that the presence of adnexal involvement in cGVHD may be associated with more severe overall cGVHD, as was shown in the pediatric population [6]. A retrospective, case–controlled study of adult HSCT recipients with skin cGVHD seen at MGH between January 2005 and October 2016 was performed to determine the prevalence of hair and nail changes in adult patients with skin cGVHD, and to investigate whether adnexal involvement in adult patients with cutaneous cGVHD is predictive of more extensive and severe overall cGVHD. IRB approval via Partners Human Research Committee was obtained. A search was performed for patients who had been coded for an ICD 9 or 10 associated with cGVHD at least once. Inclusions criteria include patients who were >18 years of age, with only one allogeneic HSCT and confirmed skin cGVHD. Subjects were excluded if they were under 18 years old, received more than one HSCT, and did not have confirmed cutaneous cGVHD. Charts of eligible patients were reviewed to determine the presence of skin cGVHD and adnexal findings. Search terms included “hair”, “alopecia”, and “nail(s)”, which helped to extract data on these findings. Additional data were collected including demographics, reason for HSCT, donor gender, GVHD severity, and other affected GVHD organs. Between January 2005 and October 2016, 474 patients with an ICD code for GVHD were seen. Of these, 193 were found to have cutaneous GVHD, with 163 meeting criteria for chronic skin GVHD. After thorough chart review, patients were assigned to one of four groups. Group 1 consisted of patients with hair and nail changes confirmed to be associated with cGVHD. The adnexal findings were substantiated by multiple, detailed references in the chart. Group 2 consisted of patients with minimal mention of hair and nail changes and unclear association with cGVHD. These charts lacked detailed clinical Co first authors: Jason S. Naftulin, Lauren R. Penzi

Hair repigmentation associated with the use of brentuximab

Brentuximab vedotin is an antibody-drug conjugate that is approved by the US Food and Drug Administration to treat refractory Hodgkin lymphoma and systemic anaplastic large cell lymphoma. Numerous clinical trials are currently evaluating the efficacy of brentuximab for other conditions, including T-cell lymphoma and steroid refractory graft-versus-host disease. Although brentuximab has been associated with various adverse effects, such as neutropenia, peripheral sensory neuropathy, fatigue, nausea, anemia, upper respiratory tract infection, diarrhea, pyrexia, rash, thrombocytopenia, cough, and vomiting, no reports exist to date of changes in hair pigmentation related to brentuximab. We report herein the first case, to our knowledge, of hair repigmentation associated with the use of brentuximab.

Hair and Nail Manifestations of Systemic Disease

Purpose of ReviewThe hair and nails provide valuable clues for physical diagnosis of systemic disease. This review provides an organ system-based framework to categorize hair and nail manifestations of systemic disease, and highlights recent discoveries in the pathobiology of appendageal disease.Recent FindingsEndocrine disorders such as polycystic ovarian syndrome can present with hirsutism and female pattern hair thinning. Autoimmune thyroid disease is associated with other autoimmune disorders like atopy, alopecia areata, and vitiligo. Cytotoxic chemotherapeutic agents result in anagen or telogen effluvium and nail changes mediated by p53, while molecular-targeted therapies like EGFR inhibitors commonly cause folliculitis and paronychia.SummaryThe hair and nails are appendageal structures of the skin that provide important physical diagnostic clues. Systemic diseases may affect their texture, color, shape, and growth. Physicians should be aware of certain pathognomonic findings that can trigger further diagnostic workup for systemic disease.