A case of diagnostic uncertainty: High-grade melanocytoma versus balloon cell melanoma in a pediatric patient.

An 11-year-old female was referred from an outside institution after a diagnostic biopsy and subsequent excision of a progressively enlarging reddish-brown nodule demonstrated features concerning for a balloon cell nevus with severe atypia versus a high-grade melanocytoma. Upon review of the initial biopsy specimen and molecular data, we favored the diagnosis to be consistent with a high-grade melanocytoma with balloon cell changes while considering the possibility of balloon cell melanoma due to concerning histopathologic and genetic abnormalities. In this case study, we discuss critical diagnostic considerations in this rare pediatric case and highlight important pathologic and clinical features of melanocytomas and balloon cell melanoma.

Development and multicenter international validation of a diagnostic tool to differentiate between pemphigoid gestationis and polymorphic eruption of pregnancy.

BACKGROUND: Pemphigoid gestationis (PG) and polymorphic eruption of pregnancy (PEP) may be similar morphologically but confer different maternal and fetal risks. Direct immunofluorescence is the gold standard test used to differentiate between the 2 diagnoses but is not always available. OBJECTIVE: To develop and validate a clinical scoring system to differentiate PG from PEP. METHODS: After developing a scoring system based on differentiating clinical factors reported in existing literature, we tested its diagnostic accuracy in a retrospective international multicenter validation study in collaboration with the European Academy of Dermatology and Venereology's Skin Diseases in Pregnancy Taskforce. RESULTS: Nineteen pregnancies (16 patients) affected by PG and 39 pregnancies (39 patients) affected by PEP met inclusion criteria. PG had a mean score of 4.6 (SD, 2.5) and PEP had a mean score of -0.3 (SD, 2.0). The area under the curve was 0.93 (95% CI, 0.86-1.00). Univariate analysis revealed that almost all criteria used in the scoring system were significantly different between the groups (P < .05), except for skip pregnancy and multiple gestations, which were then removed from the final scoring system. LIMITATIONS: Small retrospective study. CONCLUSION: The Pregnancy Dermatoses Clinical Scoring System may be useful to differentiate PG from PEP in resource-limited settings.

Pediatric lichen planus: A single-center retrospective review of 26 patients with follow up.

BACKGROUND/OBJECTIVES: Pediatric lichen planus (LP) is rare with variable prevalence and atypical presentations compared to adults. Data on LP are lacking for the pediatric population in the United States. We present demographics, presentations, and treatments for a pediatric LP cohort. METHODS: We reviewed 26 patients diagnosed with LP at 20 years or younger. Treatment responses were defined as no response, partial response, and complete response. RESULTS: Demographics included 54% females and median diagnosis age of 16 years (range 6-20). Most patients presented with cutaneous LP (65%), with fewer having associated oral (23%), nail (7.7%), or genital (3.8%) involvement. Some had cutaneous-only LP (38%) or strictly mucosal LP (oral-only 19% and genital-only 15%). LP lesions were pruritic (50%), painful (19%), and/or asymptomatic (35%). Complete/partial responses occurred with medium-potency topical corticosteroids in cutaneous (n = 7; 64%), oral (n = 3; 75%), and genital LP (n = 3; 100%), with high/ultra-high potency topical corticosteroids in oral LP (n = 6; 86%), and with topical calcineurin inhibitors in genital LP (n = 2; 100%). Side effects were clobetasol-related oral candidiasis and biopsy-related penile depressed scar. Most patients with available follow-up achieved remission (n = 17; 81%). CONCLUSIONS: Pediatric LP usually presents in adolescence with cutaneous involvement and is symptomatic. However, patients frequently can have oral, genital, or nail lesions or may be asymptomatic, so they need thorough examinations and follow-up. Long-term remission is common due to treatment or natural disease course. Medium-potency corticosteroids are recommended for cutaneous, oral, and genital LP. Various other local and systemic therapies exist with successful treatment responses.

An investigation of metabolic disturbances, including urinary stone disease, hypothyroidism, and osteoporosis in basal cell nevus syndrome.

BACKGROUND/OBJECTIVES: Basal cell nevus syndrome (BCNS) is an autosomal dominant skin cancer predisposition syndrome associated with abnormal mineral metabolism, a risk factor for urinary stone disease (USD). However, no research investigating the association between BCNS and USD or other manifestations of abnormal mineral metabolism has been conducted. The objective of this study is to investigate the association between BCNS and conditions associated with disordered mineral metabolism including USD, hypothyroidism, and osteoporosis and compare them to prevalence in the general population to elucidate potential unknown manifestations of the condition. METHODS: This retrospective study examined medical records of adult and pediatric patients with confirmed BCNS from the Mayo Clinic database from 1 January 1995 to 12 January 2020. Records were surveyed for evidence of USD and other comorbidities potentially related to BCNS. The studied cohort included 100 adult patients and 5 pediatric patients. RESULTS: A total of 105 patients were included in this analysis, 10 of whom experienced confirmed USD, representing a prevalence of 10%. Six adult patients were identified with a diagnosis of osteoporosis, representing a prevalence of 6%. Thirteen adult patients were identified with a diagnosis of hypothyroidism, representing a prevalence of 13%. CONCLUSIONS: This study identified a prevalence of USD in BCNS patients comparable to estimates of national prevalence, indicating that known abnormalities in mineral metabolism likely do not increase the incidence of USD in BCNS patients. Additional findings included increased prevalence of hypothyroidism and decreased prevalence of osteoporosis in the BCNS cohort compared to national averages.

Autoimmune progesterone dermatitis in the adolescent population.

BACKGROUND/OBJECTIVE: Autoimmune progesterone dermatitis (APD) is a rare autoimmune hypersensitivity reaction that occurs cyclically at the peak of endogenous progesterone production during the menstrual cycle in women. No study characterizing APD in the adolescent population is found; it appears likely to be underdiagnosed and undertreated. METHODS: A retrospective, single-center, review of all adolescent and pediatric patients (<20 years old at onset) with documented diagnosis of APD. RESULTS: Seventeen adolescent APD patients were included (mean age at diagnosis: 14.4 ± 2 years, mean interval of 13.6 ± 11.1 months between symptom onset and diagnosis). Twelve patients presented with urticaria, two with fixed drug eruption. Erythema multiforme, eczema, and recurrent aphthous stomatitis were present in one patient each. Exposure to exogenous progestin was present in two patients prior to disease onset. Progesterone skin test was performed in six patients with positive results in two. Fourteen patients received antihistamines and/or a topical corticosteroid. Combined oral contraceptives (COCs) were given to eleven patients, in seven via continuous daily dosing. Gonadotropin-releasing hormone agonist (GnRHa) was used in five, progesterone desensitization in four, omalizumab in two, and danazol in one patient. CONCLUSIONS: Adolescent APD is associated with a significant delay in diagnosis. The most common manifestation is urticaria. Exogenous exposure to progestins is uncommon in adolescent APD. Continuous COC, GnRHa, and progesterone desensitization have been used to control symptoms. Large, multicenter studies are required to better define, diagnose, and treat this under recognized condition among adolescent patients.

The anatomic distribution of isolated and syndrome-associated port-wine stain.

BACKGROUND/OBJECTIVES: To determine the role of sex in port-wine stain (PWS) distribution and describe the epidemiologic and anatomic differences between syndrome-associated and non-syndrome-associated PWS using modern criteria. METHODS: A retrospective review of PWS patients aged 18 years and younger from 1995 to 2018 seen in the Department of Dermatology at an academic tertiary referral center. Cases were reviewed for sex, anatomic location, and presence of associated syndrome. 4,527 records were reviewed on the basis of ICD billing codes for congenital vascular malformations, with 516 meeting inclusion criteria. RESULTS: 516 patients were included in the analysis: 234 (45.4%) men and 282 (54.6%) women. A female preponderance of Sturge-Weber syndrome (18 of 23, 78%, P = .03) and a trend toward more female-isolated PWS (149 of 269, 55%, P = .72) were found. No lateral predominance observed for isolated PWS was found: 112(41.6%) limited left-side lesions and 113(42%) limited right-side lesions (P = .41). A trend toward Klippel-Trenaunay syndrome (KTS)-associated PWS occurring more commonly isolated to the left side (76 (45.5%) vs 59 (35.12%) P = .29) was found. Nine percent of SWS patients had a PWS on the body. Five percent of KTS patients had a facial PWS. The lower limb was the most common location overall of body PWS with 33.8% of isolated PWS and 81.5% of KTS patients having a lower limb lesion. CONCLUSIONS: Female children were more likely to be diagnosed with SWS, and a trend toward more isolated PWS in women was found. No lateral predominance of isolated PWS was found, but KTS-associated PWS was more common on the left. A considerable proportion of lesions do not appear in anatomic locations traditionally considered typical in the setting of associated syndromes, which underscores the importance of conducting a complete physical examination and adhering to diagnostic criteria for those syndromes.

Tinea capitis mimicking dissecting cellulitis in three children.

Tinea capitis mimicking dissecting cellulitis is a rare presentation, and there is a paucity of information regarding this presentation in the literature. Three children 10-14 years of age who presented with an unusual clinical manifestation of tinea capitis that clinically resembled dissecting cellulitis are reported. The patients were treated with systemic antifungals for 3-4 months. Treatment success was measured according to repeat fungal cultures and clinical assessment of hair regrowth at follow-up visits. All three patients had resolution of infection, with negative repeat fungal cultures and complete hair regrowth without scarring. These cases highlight a rare inflammatory subtype of tinea capitis that can be easily misdiagnosed and therefore improperly treated, prolonging the duration of infection.

Associations of self-reported allergic diseases and musculoskeletal problems in children: A US population-based study.

BACKGROUND: Previous studies have found increased rates of musculoskeletal problems in adults with allergic disease, but whether this association holds true for children is unknown. OBJECTIVE: To investigate the association of bone, joint, and muscle problems in children with a history of allergic disease. METHODS: Data were obtained from the 2007 Child and Adolescent Health Measurement Initiative. Univariable and multivariable logistic regression models accounting for the sampling design were used to evaluate associations of bone, joint, and muscle problems with allergic diseases, such as asthma, hay fever, food allergies, and eczema. Associations were summarized with odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: The survey included 91,642 individuals aged 0 to 17 years. Multivariable modeling found statistically significant associations between the number of allergic diseases and bone, joint, and muscle problems (1 allergic disease: adjusted OR, 1.28; 95% CI, 1.04-1.56; P = .02; 2 allergic diseases: adjusted OR, 2.55; 95% CI, 1.92-3.39; P < .001; 3 allergic diseases: adjusted OR, 2.70; 95% CI, 1.88-3.86; P < .001; and 4 allergic diseases: adjusted OR, 4.35; 95% CI, 2.46-7.69; P < .001). Severe eczema (but not mild eczema) was associated with bone, joint, and muscle problems (adjusted OR, 2.81; 95% CI, 1.64-4.81; P < .001) and with bone problems (adjusted OR, 6.08; 95% CI, 1.94-19.12; P = .002). CONCLUSION: Self-reported allergic diseases in children were associated with bone, joint, and muscle problems, and associations strengthened with allergic disease severity and number of allergic diseases. Severe eczema may be associated with bone problems in children. Bone, joint, and muscle problems must be considered in children with severe allergic disease, and prospective studies are necessary to define this association.

Pediatric Pyoderma Gangrenosum: A Retrospective Review of Clinical Features, Etiologic Associations, and Treatment.

BACKGROUND/OBJECTIVES: Pyoderma gangrenosum (PG) is a neutrophilic dermatosis rarely seen in children. Its features have not been well characterized in children. We sought to characterize the clinical features, etiologic associations, and treatment of PG in children younger than 18 years. METHODS: We performed a retrospective review of children younger than 18 years with PG at the Mayo Clinic from January 1976 to August 2013. RESULTS: Thirteen children with PG were identified (n = 8; 62% female). All had ulcerations, with 62% having pustular lesions. Sites of involvement included the trunk (77%), lower extremities (77%), upper extremities (38%), and head and neck (38%). Nine (69%) had an underlying comorbidity, including seven with Crohn's disease (54%), one with juvenile idiopathic arthritis (8%), and one with pyogenic arthritis, pyoderma gangrenosum, and acne syndrome (8%). Treatments included topical or local care (92%) and systemic therapies (85%) such as oral corticosteroids (62%) and sulfasalazine or related 5-aminosalicylate drugs (46%). The clinical course did not correlate with that of the underlying systemic disease and response to treatment varied. CONCLUSION: Pediatric PG has a more varied anatomic distribution and a greater predominance of pustular lesions than PG in adults and a strong association with inflammatory bowel disease.

Atopic dermatitis: phototherapy and systemic therapy.

The majority of atopic dermatitis (AD) patients respond satisfactorily to gentle bathing, frequent moisturizing, and topical medications. Second-line therapies for AD should be used in recalcitrant cases or in patients with uncontrolled disease despite compliance with first-line measures and avoidance of allergens. Recommended advanced therapies include phototherapy, especially narrowband ultraviolet B, systemic immunosuppressants, and a new biologic agent. Few studies have compared head-to-head efficacy of the different immunosuppressant therapies such as cyclosporine, methotrexate, azathioprine and mycophenolate mofetil. Therefore, the agent used is based on provider and patient preferences and can be decided on a case-by-case basis.

Diagnosis, comorbidity, and psychosocial impact of atopic dermatitis.

Atopic dermatitis (AD) is a chronic inflammatory skin disease, with a remitting relapsing course. The central diagnostic features of AD include pruritus, xerosis, eczematous lesions with a characteristic morphology and distribution, and a personal or family history of atopic disease. Several clinical studies have emphasized the link between AD and other atopic disorders including asthma, allergic rhinitis, and food allergies. More recent studies indicate possible links between AD and other nonatopic disorders, including ADHD, sleep disturbance, and mental health disorders, suggesting an even more profound impact of this disease. Furthermore, the social, emotional, and personal impact of AD for patients and their caregivers is substantial. Understanding both the clinical characteristics and implications of AD is critical to lessening the psychosocial, clinical, and economic burden of this disease.

Curriculum United for Better Eczema Care: why, how, and what?

While various medical specialties treat eczema patients, care for these patients is largely fragmented and disorganized. Moreover, standardized treatment protocols that incorporate upcoming eczema therapies and emerging guidelines have yet to be established. Thus, there is both a need and an opportunity to equip clinicians to succeed in this novel and changing era of eczema care. The National Eczema Association's (NEA) strategic plan-developed through extensive discussions with patients who have atopic dermatitis and their caregivers, industry, and providers representing different specialties-called for the creation of an interdisciplinary coalition to steer this initiative. The Coalition United for Better Eczema Care (CUBE-C) is a network of cross-specialty leaders working to help construct an educational curriculum based on standards of effective treatment and disease management.

Atopic dermatitis: addressing allergy, infection, itch and complementary therapies.

Atopic dermatitis (AD) is a complex condition that results from the dynamic interplay between genetic predisposition, skin barrier defects, environmental factors, and a dysfunctional immune system. As a result, AD can be complicated by irritant and allergic contact dermatitis and imbalances in the skin microbiome, which can subsequently exacerbate the severity and complicate the course of preexisting atopic disease. Itch is an important symptom of AD, as it plays a large role in the quality of life of patients and their families. Since AD is a chronic, inflammatory disease that recrudesces throughout life, many have utilized alternative and/or complementary therapies, as monotherapy or in conjunction with conventional therapies, as a form of management.

Cutaneous manifestations of pediatric granulomatosis with polyangiitis: a clinicopathologic and immunopathologic analysis.

BACKGROUND: Granulomatosis with polyangiitis (GPA) is a rare systemic vasculitis associated with variable cutaneous manifestations and histopathologic findings. It is less frequent in children than adults and is often positive for cytoplasmic antineutrophil cytoplasmic antibody (ANCA) or proteinase 3-ANCA. OBJECTIVE: We sought to better define and correlate the clinical, histopathologic, and immunopathologic characteristics of cutaneous GPA in pediatric patients. METHODS: We retrospectively reviewed clinical records and cutaneous histopathologic specimens of patients 17 years or younger with cutaneous manifestations of GPA who were seen at our institution from 1990 to 2013. RESULTS: Of the 52 patients identified with GPA, cutaneous involvement occurred in 36.5% and was the initial manifestation of disease in 7.7%. Of the 19 patients with cutaneous involvement, 26.3% developed acneiform and folliculitis-like papules; 84.2% were cytoplasmic ANCA positive; and 78.9% were proteinase 3-ANCA positive. Histopathologic features included leukocytoclastic vasculitis, granulomatous inflammation, acneiform and perifollicular inflammation, granulomatous vasculitis, and palisading granulomas. LIMITATIONS: Our study was limited because of its retrospective design. CONCLUSION: Pediatric patients with cutaneous GPA most commonly have palpable purpura, leukocytoclastic vasculitis, and positive cytoplasmic ANCA or proteinase 3-ANCA serologic results. Cutaneous manifestations and histopathologic findings vary, but acneiform lesions may be a cutaneous manifestation of the disease unique to this age group.

Pediatric follicular mucinosis: presentation, histopathology, molecular genetics, treatment, and outcomes over an 11-year period at the Mayo Clinic.

Follicular mucinosis (FM) and folliculotropic mycosis fungoides (MF) are rare in children, and data regarding long-term outcomes are limited. We sought to describe clinical and histopathologic findings of children with FM with and without MF, as well as treatments administered and clinical outcomes. We conducted a retrospective chart review of patients younger than 22 years (at time of diagnosis) with a biopsy demonstrating FM who were seen in the Dermatology Department at the Mayo Clinic from September 1, 1999, to September 1, 2010. Eleven patients (six male, five female) ages 11 to 19 years at the time of diagnosis met the inclusion criteria. Follow-up data were available for 10 patients, with a mean duration of 4.9 years. The head, neck, and extremities were the most common sites of involvement, and lesions were follicular-based papules (18%), scaly alopecic patches and plaques (45%), or a combination of the two (36%). Overall, three patients were confirmed to have MF. T-cell receptor gene rearrangement demonstrated clonality in two cases and was equivocal in one case. Treatments included topical corticosteroids, topical retinoids, oral minocycline, and, in patients with MF, ultraviolet light and topical bexarotene. Lesions resolved completely in seven patients, partially in one, and not at all in two (no follow-up data on one patient). Of the three patients with MF, two had complete resolution, and one has intermittent flares. To our knowledge, no patients developed other lymphoproliferative disorders. FM in children is rare. A histopathologic diagnosis of FM does not equate to folliculotropic MF in all cases. Most patients responded to treatment with topical steroids, topical retinoids, or phototherapy. In our series of patients, the disease ran a benign course.

Updates on the dermatopathology of pregnancy-associated skin conditions.

Pathologists provide valuable input in the dermatological care of pregnant patients in various contexts. This article provides dermatopathology updates on cutaneous changes associated with pregnancy, organized based on the following classification system: physiological skin changes in pregnancy, specific dermatoses of pregnancy, dermatoses modified in pregnancy, and skin neoplasms in pregnancy. Awareness of the impact of pregnancy on the skin by pathologists is important, as this is an opportunity to contribute to diagnostic precision in this patient population.

Severe case and literature review of primary erythromelalgia: novel SCN9A gene mutation.

Erythromelalgia is a rare clinical syndrome characterized by intermittent heat, redness, swelling and pain more commonly affecting the lower extremities. Symptoms are mostly aggravated by warmth and are eased by a cold temperature. In some cases, symptoms can be very severe and disabling. Erythromelalgia can be classified as either familial or sporadic, with the familial form inherited in an autosomal dominant manner. Recently, there has been a lot of progress in studying Na(v)1.7 sodium channels (expressed mostly in the sympathetic and nociceptive small-diameter sensory neurons of the dorsal root ganglion) and different mutations affecting the encoding SCN9A gene that leads to channelopathies responsible for some disorders, including primary erythromelalgia. We present a severe case of progressive primary erythromelalgia caused by a new de novo heterozygous missense mutation (c.2623C>G) of the SCN9A gene which substitutes glutamine 875 by glutamic acid (p.Q875E). To our knowledge, this mutation has not been previously reported in the literature. We also provided a short literature review about erythromelalgia and Na(v) sodium channelopathies.