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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

A report of Epstein-Barr virus-positive primary cutaneous natural killer-/T-cell lymphoma.

We describe a patient who presented with Epstein-Barr virus-positive tumor-stage primary cutaneous lymphoma. Our patient had previously been treated with oral methotrexate for long-standing rheumatoid arthritis. Tissue analysis revealed large tumor cells that were surface CD2- and CD3-positive; T-cell-restricted intracellular antigen-positive; CD56-, CD20-, and CD30-negative; and stained positively for Epstein-Barr virus. Our case is noteworthy for several reasons. Although the presence of rheumatoid arthritis and therapy with methotrexate are putative risk factors for the development of immune suppression-related and Epstein-Barr virus-related lymphomas, the vast majority of lymphomas in this setting are of B-cell origin, and rarely are these primary cutaneous in nature. In addition, our patient's tumor displayed an unusual phenotype, with immunophenotypic features suggestive of an atypical natural killer-/T-cell lymphoma. Methotrexate was withdrawn, and our patient was successfully treated with local radiotherapy. She has remained in complete remission 28 months since diagnosis.

Mortality of bullous pemphigoid: an evaluation of 223 patients and comparison with the mortality in the general population in the United States.

BACKGROUND: There are large discrepancies in reported mortality for bullous pemphigoid (BP). OBJECTIVE: We sought to determine the mortality of a large cohort of patients with BP and compare this with age-matched control subjects. METHODS: Data were collected on 223 patients with a new diagnosis of BP between 1998 and 2003 through our cutaneous immunofluorescence laboratory databases. The mortality of patients with BP was compared with that of age-matched control subjects in the general US population. RESULTS: The 1-, 2-, and 5-year mortality was 0.23 (95% confidence interval=0.18, 0.29), 0.37 (95% confidence interval=0.31, 0.44), and 0.50 (95% confidence interval=0.42, 0.57), respectively. However, relative to age-matched control subjects, no difference in expected mortality was detected. LIMITATIONS: This was a retrospective cohort analysis. CONCLUSIONS: Mortality of patients with BP is more likely related to advanced age and associated medical conditions than to disease-specific factors.

Propionic acidemia manifesting with low isoleucine generalized exfoliative dermatosis.

We describe an infant with propionic acidemia who developed a generalized exfoliative eruption. Preceding the eruption, he was on an amino acid restricted formula. Within days of liberalizing his restricted diet, the eruption resolved completely. A similar dermatitis has been reported in infants with inborn errors of metabolism who were on amino acid modified formulas. However, in most instances, the eruption was predominantly limited to the periorificial regions. Most critical in the etiology of cutaneous eruptions in these patients is low serum isoleucine. Amino acid malnutrition should be considered in the differential diagnosis of generalized exfoliative dermatosis in an infant. Supplementation with isoleucine-containing dietary proteins results in rapid clinical resolution.

Eosinophilic folliculitis in HIV-infected women: case series and review.

BACKGROUND AND OBJECTIVE: Dermatologic conditions are often presenting signs of HIV infection and may be the sole cause of morbidity in patients who have otherwise stable HIV disease. Eosinophilic folliculitis is a pruritic, follicular eruption that typically manifests late in the course of HIV infection. Most published reports of eosinophilic folliculitis have been in HIV-infected men. In those reports, a characteristic truncal distribution was present, with involvement of the head, neck, and upper extremities commonly seen as well. The objective of this study was to better characterize the presentation of eosinophilic folliculitis in women. METHODS: We conducted a retrospective chart review of six HIV-seropositive women with eosinophilic folliculitis previously seen in our dermatology clinics. We also reviewed the literature for cases of eosinophilic folliculitis in women and for clinical and therapeutic aspects of the condition, particularly in women. RESULTS: In our case series, we found that eosinophilic folliculitis in women may predominantly affect the face and mimic acne excoriée. A review of the literature of HIV-associated eosinophilic folliculitis in women supports these findings. Regarding treatment, many therapies are available, but none is uniformly effective. CONCLUSION: Given the dramatic rise in the incidence of HIV infection in women, who now represent nearly 50% of adults living worldwide with HIV/AIDS, a heightened awareness of HIV-related dermatoses in women is essential. HIV-associated eosinophilic folliculitis should be considered in the differential diagnosis of chronic, pruritic, papular facial eruptions in females.

Intravenous cidofovir-induced resolution of disfiguring cutaneous human papillomavirus infection.

Human papillomavirus infection is one of the most common and most distressing cutaneous diseases in patients with HIV infection. It is also a common, and often therapeutically challenging, infection in individuals who are immunologically competent. A wide range of therapeutic options exists for treating cutaneous human papillomavirus infections, but none is uniformly effective. In this report we describe a man with HIV-1 infection and disfiguring facial verruca vulgaris who demonstrated complete clinical response to intravenous cidofovir. Our report provides further support for the use of intravenous cidofovir as therapy for treatment-resistant and/or widespread cutaneous human papillomavirus infection.

Treatment of cutaneous T-cell lymphoma/mycosis fungoides.

The cause of mycosis fungoides is unknown and, with the possible exception of very early stage disease, no cure is available. Fortunately, patients with MF have a number of therapeutic options and partial and complete remissions are achievable. Because it is not curable, the burden for patients with this disease involves the need for lifelong therapy and monitoring, and meticulous skin care. Despite its indolent nature in most individuals, the disease has a tremendous psychological impact, not only because of the visible nature of the skin lesions, but also due to the rarity of the disease and its chronicity. Knowledge of this disease, therapeutic options, and expectations of therapy will enhance care of patients afflicted with mycosis fungoides. Ongoing research provides hope that in the future, therapy to induce long-lasting remission, or even cure, will become available. Since the submission of this manuscript, vorinostat (Zolinza), an orally administered histone inhibitor, has been FDA approved for treating skin manifestations in patients with CTCL.

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.