Racial Disparities in the Incidence of Primary Chronic Cutaneous Lupus Erythematosus in the Southeastern US: The Georgia Lupus Registry.

OBJECTIVE: Relative to studies of systemic lupus erythematosus (SLE), epidemiologic studies of chronic cutaneous lupus erythematosus (CCLE) are rare and are limited to populations with no racial diversity. We sought to provide minimum estimates of the incidence of primary CCLE (CCLE in the absence of SLE) in a population comprised predominantly of white individuals and black individuals in the southeastern region of the US. METHODS: The Georgia Lupus Registry allowed for the use of multiple sources for case-finding, including dermatology and rheumatology practices, multispecialty health care facilities, and dermatopathology reports. Cases with a clinical or clinical/histologic diagnosis of CCLE were classified as definite. Cases ascertained exclusively from dermatopathology reports were categorized as probable. Age-standardized incidence rates stratified by sex and race were calculated for discoid lupus erythematosus (DLE) in particular and for CCLE in general. RESULTS: The overall age-adjusted estimates for combined (definite and probable) CCLE were 3.9 per 100,000 person-years (95% confidence interval [95% CI] 3.4-4.5). The overall age-adjusted incidences of definite and combined DLE were 2.9 (95% CI 2.4-3.4) and 3.7 (95% CI 3.2-4.3) per 100,000 person-years, respectively. When capture-recapture methods were used, the age-adjusted incidence of definite DLE increased to 4.0 (95% CI 3.2-4.3). The black:white and female:male incidence ratios for definite DLE were 5.4 and 3.1, respectively. CONCLUSION: Our findings underscore the striking racial disparities in susceptibility to primary CCLE, with black individuals having a 3-fold to 5-fold increased incidence of CCLE in general, and DLE in particular, compared with white individuals. The observed sex differences were consistent with those reported previously, with a 3 times higher risk of DLE in women compared with men.

Multiple morphologically distinct cutaneous granular cell tumors occurring in a single patient.

Granular cell tumors (GCTs) typically are benign solitary tumors derived from Schwann cells. The tongue and skin are the most common sites of involvement; however, lesions also can develop in viscera such as the gastrointestinal tract. Multiple cutaneous GCTs in a single patient have been reported, with the lesions being described as subcutaneous papules, nodules, or verrucous nodules. We report the case of a patient who presented with several simultaneously occurring cutaneous GCTs with morphologically distinct clinical appearances ranging from subcutaneous nodules with no overlying epidermal alteration to exophytic moist nodules with eroded surfaces. Histopathology of several lesions was diagnostic of GCTs. This case illustrates the highly varied clinical presentation and morphology of cutaneous GCTs, even those occurring in a single patient. In addition to mimicking other benign neoplasms, GCTs may mimic other disease processes, including malignant lesions, infections, and inflammatory disorders. Skin biopsy generally is required for definitive diagnosis.

Folliculotropic Mycosis Fungoides as a Posttransplant Lymphoproliferative Disorder.

Posttransplant lymphoproliferative disorder (PTLD) is a known complication of solid organ transplantation. The majority are B cell in origin and related to Epstein-Barr virus infection. T-cell PTLD is much less common; most are Epstein-Barr virus negative and have a worse prognosis. Primary cutaneous T-cell lymphoma (CTCL) as a presentation of PTLD is rare. CTCL has a less favorable prognosis in transplant patients compared with that in immune-competent patients. Herein, we report a case of a 13-year-old boy who developed folliculotropic mycosis fungoides, a rare subtype of CTCL, subsequent to renal transplantation. To our knowledge, this is the first report of this type of PTLD in a pediatric patient.

Total skin electron therapy for cutaneous T-cell lymphoma using a modern dual-field rotational technique.

PURPOSE: To report our experience with rotational total skin electron irradiation (RTSEI) in cutaneous T-cell lymphoma (CTCL), and to examine response by disease stage and race. METHODS AND MATERIALS: We reviewed our outcomes for 68 CTCL patients who received RTSEI (≥ 30 Gy) from 2000 to 2013. Primary outcomes were complete clinical response (CCR), recurrence-free survival (RFS), and overall survival (OS). Using log-rank tests and Cox proportional hazards, OS and RFS were compared across tumor stages at time of RTSEI with further racial subgroup analysis. RESULTS: Median age at diagnosis and at time of radiation was 52 and 56 years, respectively. Median follow-up was 5.1 years, 49% were African American, and 49% were female. At time of treatment, 18, 37, and 13 patients were T stage 2, 3, and 4, respectively. At 6 weeks after RTSEI, overall CCR was 82% (88%, 83%, and 69% for T2, T3, and T4, respectively). Median RFS was 11 months for all patients and 14, 10, and 12 months for stage T2, T3, and T4, respectively. Tumor stage was not associated with RFS or CCR. Maintenance therapy after RTSEI was associated with improved RFS in both crude and multivariable analysis, controlling for T stage. Median OS was 76 months (91 and 59 months for T3 and T4, respectively). With the exception of improved OS in African Americans compared with whites at stage T2, race was not associated with CCR, RFS, or OS. CONCLUSIONS: These results represent the largest RTSEI clinical outcomes study in the modern era using a dual-field rotational technique. Our observed response rates match or improve upon the standard set by previous outcome studies using conventional TSEI techniques, despite a large percentage of advanced CTCL lesions in our cohort. We found that clinical response after RTSEI did not seem to be affected by T stage or race.

Clinical characteristics, prognostic factors, and survival of 393 patients with mycosis fungoides and Sézary syndrome in the southeastern United States: a single-institution cohort.

BACKGROUND: Limited data exist on patients with mycosis fungoides (MF) and Sézary syndrome (SS) from the southeastern United States, a region with a high proportion of African Americans (AA). OBJECTIVES: We sought to determine clinical characteristics, prognostic factors, and survival of patients with MF/SS in a southeastern US cohort, compare with other cohorts, and validate proposed revisions in MF/SS staging. METHODS: This was a retrospective chart review of patients from an academic dermatology referral center (Atlanta, GA) from 1998 to 2013. Kaplan-Meier estimates were calculated for overall survival, disease-specific survival, and progression; univariate and multivariate Cox proportional hazard models were used for assessment of prognostic variables. RESULTS: Of 393 patients, 55.2% were white, 43.3% AA, and 1.5% other; 52.7% were male and 47.3% female (ratio 1.1:1). Mean age was 53.6 years; mean age among AA was 48.9 years. In all, 19.6% died of disease; 21.9% experienced disease progression. Advanced TNMB classification, presence of a circulating clone without phenotypic evidence of blood involvement, and older age were predictors of poor disease-specific survival in the multivariate analysis, whereas AA race was not. LIMITATIONS: This study was from a single academic center. CONCLUSIONS: Outcomes of our patients generally paralleled those of other geographic regions. MF/SS may affect younger patients and more women than previously recognized, particularly among AA. Survival among AA may be more favorable than that observed in prior reports. Our data support the validity of the staging criteria revisions for MF/SS.

The skin and HIV: no superficial matter.

The vast majority of HIV-infected patients experience some type of skin disorder; these may broadly be categorized as infectious, neoplastic, or inflammatory. Additionally, primary pruritus afflicts a considerable percentage of HIV-infected individuals, and an attempt should be made to identify potential underlying triggers. Chronic itch, whether related to an underlying cutaneous, systemic, or psychiatric illness, can have a profound effect on quality of life. Therapy for inflammatory skin disorders may involve initiation of antiretroviral therapy in those who have not yet started such treatment, oral antihistamines, topical corticosteroids, topical antipruritic agents, and skin moisturizers. Because topical corticosteroids are often a necessary component of the therapeutic armamentarium for skin diseases, practitioners are encouraged to become familiar with the appropriate indications, strengths, and formulations of available preparations. In some instances, psychiatric medications or phototherapy may be necessary for the treatment of HIV-associated skin disorders, particularly for patients experiencing refractory itch. Although psoriasis is not more frequent among HIV-infected patients than in the general population, it can be more severe and debilitating for those who are HIV infected. Our understanding of psoriasis in the setting of HIV infection has evolved and new therapies for psoriasis have recently become available. This article summarizes a presentation by Sareeta R. S. Parker, MD, at the IAS-USA continuing education program held in Atlanta, Georgia, in April 2014.

Bullous systemic lupus erythematosus in a patient with human immunodeficiency virus infection: a paradox of autoimmunity and immunodeficiency.

Bullous lupus erythematosus is a rare variant of systemic lupus erythematosus (SLE) and is characterized by autoantibodies to type VII collagen. Co-existence of SLE and human immunodeficiency virus (HIV) infection is extremely rare; the development of bullous lupus in the setting of HIV has been, to our knowledge, reported in the literature only once. We describe a 26-year-old man with an 8-year history of HIV infection who developed bullous SLE. The patient presented with widespread, tense bullae as well as oral ulcerations. Clinical, laboratory, histological, and cutaneous immunofluorescence findings confirmed the diagnosis of bullous SLE. Given the immunological consequence of HIV infection, the co-occurrence of these two diseases would, theoretically, be unusual. Theories pertaining to the interplay of immunologic mechanisms of the seemingly paradoxical occurrence of autoimmunity in the setting of HIV infection are discussed.

Is non-alcoholic steatohepatitis a predisposing factor to porphyria cutanea tarda?

Porphyria cutanea tarda (PCT) is a disease caused by a deficiency of the fifth enzyme of the heme biosynthetic pathway in the liver that manifests in the skin as blistering and fragility of predominantly sun-exposed skin. It occurs in individuals with environmental and/or genetic risk factors such as estrogen use, hepatitis C infection and hemochromatosis gene mutations. This report highlights a case of PCT which manifested in an individual with non-alcoholic fatty liver disease (non-alcoholic steatohepatitis; NASH). We propose that NASH may have been a contributing factor for the development of PCT in our patient.

The head, neck, and systemic manifestations of levamisole-adulterated cocaine use.

Systemic complications of levamisole-adulterated cocaine (LAC) use have recently been described. The objective of this review is to increase awareness of these manifestations among oral and maxillofacial surgeons. LAC exposure through inhalation, nasal insufflation, or injection can induce cutaneous vasculopathy and hematologic abnormalities such as neutropenia or agranulocytosis. Unlike other vasculopathies involving the skin, LAC-induced vascular injury frequently manifests with purpuric and necrotic lesions that involve the face and ears. Oral manifestations have also been reported but are not yet well characterized. The aforementioned hematologic manifestations are not uncommon, and patients exposed to LAC are potentially at higher risk for infectious complications. When manifestations of LAC affect the head, neck, and oral cavity, oral and maxillofacial surgeons may be the first providers to encounter the patient. Early recognition of the clinical signs and laboratory abnormalities will better allow for distinguishing LAC-related effects from various clinical mimics, will facilitate appropriate patient management, and may further contribute to the understanding of the biological effects of LAC.

Acitretin for the treatment of cutaneous T-cell lymphoma.

BACKGROUND: Bexarotene is the only Food and Drug Administration-approved retinoid for the treatment of cutaneous T-cell lymphoma (CTCL) and is associated with a relatively high frequency of adverse effects. Acitretin has anecdotally been reported to be effective for CTCL. OBJECTIVE: We sought to determine the effectiveness and tolerability of acitretin as primary or adjuvant therapy for CTCL. METHODS: We conducted a retrospective chart review of patients with CTCL treated with acitretin at a single tertiary care center. RESULTS: A total of 32 patients with CTCL were included: 29 had mycosis fungoides, 2 had Sézary syndrome, and 1 had CTCL not otherwise specified. Median patient age was 55 years; 56% were male; 47% were white, 47% black, and 6% other. In all, 3% of patients were stage IA, 69% stage IB/IIA, 16% stage IIB, 6% stage III, and 6% stage IV. Six patients received acitretin alone; 26 received acitretin in addition to another CTCL therapy. The overall response rate was 59%. In all, 25% of patients had stable disease and 16% had progressive disease. Median duration of response was 28 months. Adverse effects were generally mild with 5 patients discontinuing therapy because of these. LIMITATIONS: In this small retrospective chart review, many patients were on other CTCL therapies while on acitretin; therefore precise assessment of response to acitretin alone was difficult. CONCLUSIONS: Acitretin is well tolerated and potentially effective for early-stage CTCL. Response to acitretin, either as adjuvant therapy monotherapy, is comparable with the response to oral agents currently approved for this disease.

Hodgkin lymphoma presenting as generalized pruritus in an adolescent.

Pruritus is a common manifestation of Hodgkin lymphoma (HL), and given its high frequency, inclusion of itching as a B symptom of HL has been proposed. We present a 16-year-old adolescent boy with treatment-refractory eczema of 2 years' duration. Physical examination revealed a thin adolescent boy with widespread excoriations, but no eczematous or primary cutaneous lesions were identifiable. Lymph node examination revealed palpably enlarged nodes in the cervical and supraclavicular regions. Laboratory studies revealed leukocytosis and an elevated lactate dehydrogenase level. Diffuse lymphadenopathy was detected on a chest radiograph, and excisional lymph node biopsy revealed HL (nodular sclerosing subtype). The patient was classified as HL stage IIIB (Ann Arbor staging classification) after further evaluation. Chemotherapy was initiated followed by radiation therapy. The patient's pruritus markedly improved within 2 cycles of chemotherapy; however, his HL relapsed and additional salvage combination chemotherapy followed by high-dose chemotherapy and autologous stem cell transplant were required. This case underscores the need for a complete history as well as a careful skin and systemic evaluation in patients presenting with long-term pruritus, including children and adolescents.

Clinical end points and response criteria in mycosis fungoides and Sézary syndrome: a consensus statement of the International Society for Cutaneous Lymphomas, the United States Cutaneous Lymphoma Consortium, and the Cutaneous Lymphoma Task Force of the European Organisation for Research and Treatment of Cancer.

Mycosis fungoides (MF) and Sézary syndrome (SS), the major forms of cutaneous T-cell lymphoma, have unique characteristics that distinguish them from other types of non-Hodgkin's lymphomas. Clinical trials in MF/SS have suffered from a lack of standardization in evaluation, staging, assessment, end points, and response criteria. Recently defined criteria for the diagnosis of early MF, guidelines for initial evaluation, and revised staging and classification criteria for MF and SS now offer the potential for uniform staging of patients enrolled in clinical trials for MF/SS. This article presents consensus recommendations for the general conduct of clinical trials of patients with MF/SS as well as methods for standardized assessment of potential disease manifestations in skin, lymph nodes, blood, and visceral organs, and definition of end points and response criteria. These guidelines should facilitate collaboration among investigators and collation of data from sponsor-generated or investigator-initiated clinical trials involving patients with MF or SS.

Autoimmune blistering diseases in the elderly.

Autoimmune blistering diseases are a significant cause of morbidity and mortality in the elderly population. Given the advancing age of the population, the incidence of these disorders, particularly bullous pemphigoid, is expected to rise. This contribution reviews autoimmune immunobullous disorders of particular relevance in the elderly population. These include bullous pemphigoid, cicatricial pemphigoid, epidermolysis bullosa acquisita, pemphigus, paraneoplastic pemphigus, and linear immunoglobulin A bullous dermatosis. Because therapy and management of individual immunobullous dermatoses differ, establishing the diagnosis is often critically important. An overall approach to bullous diseases in the elderly, as well as key clinical features, appropriate diagnostic tests, microscopic findings, immunofluorescence microscopy patterns, and molecular targets for select disorders are reviewed. Elucidation of antigenic targets at the molecular level has allowed for development of serum enzyme-linked immunofluorescence assays, which have enhanced diagnostic accuracy for several autoimmune blistering disorders. Given the relative rarity of these diseases, large randomized trials evaluating efficacy of various treatments are few, and therapy for most immunobullous disorders in the elderly has not been standardized. Despite this, appropriate therapeutic considerations for each condition are presented and the evidence for them is reviewed.

Sézary syndrome: immunopathogenesis, literature review of therapeutic options, and recommendations for therapy by the United States Cutaneous Lymphoma Consortium (USCLC).

Sézary syndrome (SS) has a poor prognosis and few guidelines for optimizing therapy. The US Cutaneous Lymphoma Consortium, to improve clinical care of patients with SS and encourage controlled clinical trials of promising treatments, undertook a review of the published literature on therapeutic options for SS. An overview of the immunopathogenesis and standardized review of potential current treatment options for SS including metabolism, mechanism of action, overall efficacy in mycosis fungoides and SS, and common or concerning adverse effects is first discussed. The specific efficacy of each treatment for SS, both as monotherapy and combination therapy, is then reported using standardized criteria for both SS and response to therapy with the type of study defined by a modification of the US Preventive Services guidelines for evidence-based medicine. Finally, guidelines for the treatment of SS and suggestions for adjuvant treatment are noted.

Ulcerative granulomatous mycosis fungoides.

A 42-year-old white male military recruit presented with a 2-year history of painful ulcerations on the skin of his flanks and thighs. Prior skin biopsies were nondiagnostic but raised the suspicion of an infectious etiology due to the presence ofa granulomatous infiltrate. His medical history was significant for herpes zoster and eczema, and, on review of systems, he had a 1-year history of progressive fatigue and night sweats. Examination revealed approximately one dozen 1- to 5-cm indurated, dusky violaceous plaques on his trunk and lower extremities. Several of the plaques, including one on his right flank, had overlying deep ulcerations (Figure 1A and 1B). Bilateral inguinal lymphadenopathy was present.

Pityriasis lichenoides chronica in black patients.

Pityriasis lichenoides chronica (PLC) is a cutaneous disease of unknown etiology that most commonly affects children and young adults. The highly variable presentation of this condition often poses a diagnostic challenge. The clinical presentation of PLC in black patients is not well described. We report a series of 5 black patients (4 children and 1 young adult) with PLC who presented with extensive hypopigmentation and prominent facial involvement. One patient had concomitant mycosis fungoides (MF). The diagnosis of PLC should be included in the differential diagnosis in dark-skinned patients who present with widespread hypopigmented macules and patches. The presence of MF in one of our patients underscores the potential relationship between MF and PLC.

Follicular mucinosis: clinical, histologic, and molecular remission with minocycline.

Follicular mucinosis is an uncommon inflammatory disorder characterized histologically by mucin accumulation in the follicular epithelium. The condition is generally divided into primary and secondary forms, the latter being frequently associated with mycosis fungoides. Lesional skin T-cell clonality has been documented in some patients with follicular mucinosis, even those with no histologic evidence of cutaneous lymphoma. In this report, we describe a patient with clonal idiopathic primary follicular mucinosis who had complete clinical, histologic, and molecular remission with minocycline therapy.

Evaluation of the long-term tolerability and clinical benefit of vorinostat in patients with advanced cutaneous T-cell lymphoma.

INTRODUCTION: Vorinostat, an orally active histone deacetylase inhibitor, was approved in October 2006 by the US Food and Drug Administration for the treatment of cutaneous manifestations of cutaneous T-cell lymphoma (CTCL) in patients with progressive, persistent, or recurrent disease during or after treatment with 2 systemic therapies. PATIENTS AND METHODS: A multicenter, open-label phase IIb trial evaluated the activity and safety of vorinostat 400 mg orally daily in patients with > or = stage IB, persistent, progressive, or treatment-refractory mycosis fungoides or Sézary syndrome CTCL subtypes. We report the safety and tolerability of long-term vorinostat therapy in patients who experienced clinical benefit in the previous phase IIb study. RESULTS: As of December 11, 2008, 6 of 74 patients enrolled in the original study had received vorinostat for > or = 2 years: median age, 65 years; median number of previous therapies, 2.5; median time from diagnosis to enrollment, 1.8 years. At enrollment into the continuation phase, 5 of the 6 patients had achieved an objective response, and 1 patient had prolonged stable disease. During the follow-up study, the most common drug-related grade 1-4 adverse events (AEs) were diarrhea, nausea, fatigue, and alopecia (6, 5, 4, and 3 patients, respectively). Incidence of grade 3/4 AEs was low: anorexia (n = 1), increased creatinine phosphokinase (n = 1), pulmonary embolism (n = 1), rash (n = 1), and thrombocytopenia (n = 1). Five patients have discontinued the study drug, and 1 patient is continuing therapy. CONCLUSION: This post hoc subset analysis provides evidence for the long-term safety and clinical benefit of vorinostat in heavily pretreated patients with CTCL, regardless of previous treatment failures.