Clinical Features of Cutaneous Paraneoplastic Syndromes in Hodgkin Lymphoma.

Cutaneous paraneoplastic syndromes due to Hodgkin lymphoma present with a wide spectrum of clinical manifestations from generalized pruritus to exfoliative erythroderma. We summarize the clinical findings and outcomes of 14 patients with Hodgkin lymphoma and associated cutaneous paraneoplastic syndromes treated at Mayo Clinic over the past 3 decades. Cutaneous paraneoplastic syndromes may be present at the time of lymphoma diagnosis, whereas in other patients, it may appear at the time of relapse, including patients with initial absence of cutaneous manifestations during the initial lymphoma presentation. Our results indicate that complete resolution of the paraneoplastic syndrome is associated with significantly improved overall survival. Recognition of cutaneous paraneoplastic syndromes is a crucial surrogate of relapsed malignancy and treatment requires targeting the underlying malignancy.

A Review of Oral Therapies for the Treatment of Skin Hyperpigmentation.

This review article examines evidence supporting the use of oral therapies in treating idiopathic, actinic, and metabolically induced skin hyperpigmentation. A thorough review of the literature regarding oral treatments for hyperpigmentation was systematically conducted through PubMed. Keywords used in the primary search include "Hyperpigmentation," "Melanosis" or "Melasma," "Lightening," "Oral," and "Therapeutics." The search was limited to the English language, and no timeframe restrictions were implemented. Numerous orally administered therapies have been proposed for the treatment of skin hyperpigmentation. There is an abundant body of literature demonstrating the efficacy of orally administered tranexamic acid, glutathione, isotretinoin, and proanthocyanidin. It is reasonable to expect that the most effective oral therapies will address known underlying causes of hyperpigmentation such as thyroid disease, diabetes, and hormonal imbalance. Improvement due to oral therapy of otherwise unresponsive skin hyperpigmentation or hyperpigmentation of unknown cause is less predictable. This review is limited by the strength of evidence contained within the available studies. Clinical studies investigating the treatments discussed within this article are limited in number, at times lack blinding in the study design, and are based on small sample sizes. Based on existing research, the most promising oral remedies for hyperpigmentation appear to be tranexamic acid, glutathione, isotretinoin, and proanthocyanidin. Additional studies to better establish safety and efficacy are necessary.

How to Sequence Therapies in Mycosis Fungoides.

OPINION STATEMENT: Choice of therapy in mycosis fungoides is based on both patient- and lymphoma-specific factors, such as disease characteristics, comorbidities, symptoms and effect on quality of life, potential associated toxicities of therapy, response and tolerance to prior lines of therapy, and convenience and practicality. Generally, we sequence therapies from least toxic, targeted, nonimmunosuppressive to more toxic, immunosuppressive and from single agent to multiple agents, as necessary. If more toxic, immunosuppressive agents are required to alleviate disease burden or symptoms, we generally use them just long enough to control the disease, then transition to a maintenance regimen with less toxic, less immunosuppressive agents.

Leprosy as a Diagnostic Challenge in the United States.

A 63-year-old woman from Central Florida presented to an outside clinic with a 2-year history of a progressive, asymptomatic cutaneous eruption and arthralgias. Her past medical history was significant for reported seronegative rheumatoid arthritis, for which adalimumab, methotrexate, and low-dose prednisone therapy were initiated 5 years prior. The skin eruption occurred shortly after a 4-week hospitalization during which these medications were withheld. At her initial outside evaluation, a biopsy was performed and interpreted as subacute cutaneous lupus erythematosus (SCLE). She was treated with hydroxychloroquine without improvement. A repeat biopsy was reported as consistent with interstitial granulomatous dermatitis (IGD). There was no improvement with potent topical corticosteroids.

Epidermolytic hyperkeratosis of the vulva.

Vulvar epidermolytic hyperkeratosis is a benign entity that mimics other malignant and inflammatory vulvar dermatoses clinically and histologically requiring careful clinical pathologic correlation for diagnosis.

Identification of stage I/IIA melanoma patients at high risk for disease relapse using a clinicopathologic and gene expression model.

PURPOSE: Patients with stage I/IIA cutaneous melanoma (CM) are currently not eligible for adjuvant therapies despite uncertainty in relapse risk. Here, we studied the ability of a recently developed model which combines clinicopathologic and gene expression variables (CP-GEP) to identify stage I/IIA melanoma patients who have a high risk for disease relapse. PATIENTS AND METHODS: Archival specimens from a cohort of 837 consecutive primary CMs were used for assessing the prognostic performance of CP-GEP. The CP-GEP model combines Breslow thickness and patient age, with the expression of eight genes in the primary tumour. Our specific patient group, represented by 580 stage I/IIA patients, was stratified based on their risk of relapse: CP-GEP High Risk and CP-GEP Low Risk. The main clinical end-point of this study was five-year relapse-free survival (RFS). RESULTS: Within the stage I/IIA melanoma group, CP-GEP identified a high-risk patient group (47% of total stage I/IIA patients) which had a considerably worse five-year RFS than the low-risk patient group; 74% (95% confidence interval [CI]: 67%-80%) versus 89% (95% CI: 84%-93%); hazard ratio [HR] = 2.98 (95% CI: 1.78-4.98); P < 0.0001. Of patients in the high-risk group, those who relapsed were most likely to do so within the first 3 years. CONCLUSION: The CP-GEP model can be used to identify stage I/IIA patients who have a high risk for disease relapse. These patients may benefit from adjuvant therapy.

Model Combining Tumor Molecular and Clinicopathologic Risk Factors Predicts Sentinel Lymph Node Metastasis in Primary Cutaneous Melanoma.

PURPOSE: More than 80% of patients who undergo sentinel lymph node (SLN) biopsy have no nodal metastasis. Here we describe a model that combines clinicopathologic and molecular variables to identify patients with thin and intermediate thickness melanomas who may forgo the SLN biopsy procedure due to their low risk of nodal metastasis. PATIENTS AND METHODS: Genes with functional roles in melanoma metastasis were discovered by analysis of next generation sequencing data and case control studies. We then used PCR to quantify gene expression in diagnostic biopsy tissue across a prospectively designed archival cohort of 754 consecutive thin and intermediate thickness primary cutaneous melanomas. Outcome of interest was SLN biopsy metastasis within 90 days of melanoma diagnosis. A penalized maximum likelihood estimation algorithm was used to train logistic regression models in a repeated cross validation scheme to predict the presence of SLN metastasis from molecular, clinical and histologic variables. RESULTS: Expression of genes with roles in epithelial-to-mesenchymal transition (glia derived nexin, growth differentiation factor 15, integrin ß3, interleukin 8, lysyl oxidase homolog 4, TGFß receptor type 1 and tissue-type plasminogen activator) and melanosome function (melanoma antigen recognized by T cells 1) were associated with SLN metastasis. The predictive ability of a model that only considered clinicopathologic or gene expression variables was outperformed by a model which included molecular variables in combination with the clinicopathologic predictors Breslow thickness and patient age; AUC, 0.82; 95% CI, 0.78-0.86; SLN biopsy reduction rate of 42% at a negative predictive value of 96%. CONCLUSION: A combined model including clinicopathologic and gene expression variables improved the identification of melanoma patients who may forgo the SLN biopsy procedure due to their low risk of nodal metastasis.

Valchlor® in the Treatment of Lichen Planopilaris and Frontal Fibrosing Alopecia: A Single Arm, Open-label, Exploratory Study.

BACKGROUND: Lichen Planopilaris (LPP) is a lymphocyte-mediated scarring alopecia that frequently is treatment resistance to both topical and systemic therapies. AIMS AND OBJECTIVES: The object of this pilot study was to assess the effectiveness of topical mechlorethamine 0.016% gel (Valchlor®) in decreasing disease activity in LPP and the related clinical variant frontal fibrosing alopecia (FAA). METHODS: Twelve patients with biopsy-proven LPP/FAA who failed prior topical or systemic therapy with active disease were included. Participants applied mechlorethamine 0.016% gel to involved areas daily for 24 weeks. Outcome measures included LPP Activity Index (LPPAI) score, Physician Global Assessment (PGA) score, Dermatology Quality of Life Index (DQLI) score, and phototrichograms assessing follicular counts before and after six months of therapy. RESULTS: LPP Activity Index (LPPAI) before and after treatment was significantly different (5.0 before treatment, 2.0 after treatment; p value=0.006). Mean follicular density and follicular units were unchanged during the treatment period. CONCLUSION: Treatment with mechlorethamine 0.016% gel for 24 weeks resulted in statistically significant improvement of LLP/FFA with no change in phototrichogram parameters. Treatment duration was limited by high rate of contact dermatitis. Further investigation to optimize dosing frequency and to assess the role of combination topical therapy is needed.

Chronic Eroded Perianal Plaque in a Patient with Limited Systemic Scleroderma.

A 58-year-old African-American woman presented with a variably painful perianal eruption for 5 years (Figure 1). Prior treatment with topical zinc oxide, oral fluconazole, and Amoxicillin/clavulanic acid resulted in no improvement. She denied chronic diarrhea or cutaneous blistering. Past medical history included limited scleroderma and autoimmune hemolytic anemia treated with daily azathioprine; however, the eruption preceded iatrogenic immunosuppression. Physical examination revealed a well-defined glistening red, ovoid focally eroded plaque involving the intergluteal cleft. The vulva was uninvolved. Oral mucosa was also clear.

Association of antinuclear antibody status with clinical features and malignancy risk in adult-onset dermatomyositis.

BACKGROUND: The clinical significance of antinuclear antibody (ANA) status in adults with dermatomyositis (DM) has yet to be fully defined. OBJECTIVE: We compared the incidence of amyopathic disease, risk of malignancy, and clinical findings in ANA+ and ANA- patients with adult-onset DM. METHODS: This was a retrospective cohort study of patients with ANA+ or ANA- adult-onset DM determined by enzyme-linked immunosorbent assay. RESULTS: Of 231 patients, 140 (61%) were ANA+ and 91 (39%) were ANA-. Compared with the ANA- patients, the ANA+ patients had a lower frequency of dysphagia (15% vs 26% [P = .033]) and heliotrope rash (38% vs 53% [P = .026]). In all, 54 patients (23%) developed malignancy within 3 years of diagnosis of their DM; 11% of the ANA+ patients developed malignancy versus 43% of the ANA- patients (P < .001). There was a strong association between ANA positivity and lower likelihood of malignancy in multivariable analysis (odds ratio, 0.16; P < .001). Conversely, ANA positivity was not associated with amyopathic disease (odds ratio, 0.94; P = .87). LIMITATIONS: The retrospective nature of the study was a limitation. CONCLUSION: In patients with adult-onset DM, ANA negativity is associated with increased likelihood of development of malignancy within 3 years of diagnosis of their DM. Particularly close follow-up and frequent malignancy screening may be warranted in ANA- individuals with DM.

SCLEROMYXEDEMA WITH RETINAL VASCULITIS AND MACULAR EDEMA.

BACKGROUND/PURPOSE: To describe the findings and clinical course of a patient with scleromyxedema complicated by retinal vasculitis and macular edema. METHODS: Interventional case report. RESULTS: A 64-year old Caucasian woman with recently diagnosed, biopsy proven scleromyxedema presented with decreased visual acuity (20/50 OD; 20/100 OS) due to retinal vasculitis and macular edema. She received intravitreal bevacizumab and subtenon's triamcinolone acetonide for the macular edema, and bilateral pars plana vitrectomies were required for vitreous hemorrhages. Monthly intravenous infusions of immunoglobulins (IVIG) resulted in resolution of the macular edema and vasculitis, and stabilization of the VA (20/40 OD; counting fingers at 6 feet OS). CONCLUSION: Scleromyxedema may be complicated by retinal vasculitis and macular edema. Treatment with corticosteroids and vascular endothelial growth factor inhibitors may be minimally effective but IVIG should be considered for both the ocular and systemic findings.