Sareeta Parker

Phase IIB Multicenter Trial of Vorinostat in Patients With Persistent, Progressive, or Treatment Refractory Cutaneous T-Cell Lymphoma

PURPOSE To evaluate the activity and safety of the histone deacetylase inhibitor vorinostat (suberoylanilide hydroxamic acid) in persistent, progressive, or recurrent mycosis fungoides or Sézary syndrome (MF/SS) cutaneous t-cell lymphoma (CTCL) subtypes. PATIENTS AND METHODS Patients with stage IB-IVA MF/SS were treated with 400 mg of oral vorinostat daily until disease progression or intolerable toxicity in this open-label phase IIb trial (NCT00091559). Patients must have received at least two prior systemic therapies at least one of which included bexarotene unless intolerable. The primary end point was the objective response rate (ORR) measured by the modified severity weighted assessment tool and secondary end points were time to response (TTR), time to progression (TTP), duration of response (DOR), and pruritus relief ( > or = 3-point improvement on a 10-point visual analog scale). Safety and tolerability were also evaluated. RESULTS Seventy-four patients were enrolled, including 61 with at least stage IIB disease. The ORR was 29.7% overall; 29.5% in stage IIB or higher patients. Median TTR in stage IIB or higher patients was 56 days. Median DOR was not reached but estimated to be >or = 185 days (34+ to 441+). Median TTP was 4.9 months overall, and 9.8 months for stage IIB or higher responders. Overall, 32% of patients had pruritus relief. The most common drug-related adverse experiences (AE) were diarrhea (49%), fatigue (46%), nausea (43%), and anorexia (26%); most were grade 2 or lower but those grade 3 or higher included fatigue (5%), pulmonary embolism (5%), thrombocytopenia (5%), and nausea (4%). Eleven patients required dose modification and nine discontinued due to AE. CONCLUSION Oral vorinostat was effective in treatment refractory MF/SS with an acceptable safety profile.

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.

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.

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.

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.

Propionic Acidemia Manifesting with Low Isoleucine Generalized Exfoliative Dermatosis

Abstract:  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.

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.

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.

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.

Eosinophilic Folliculitis in HIV-Infected Women

AbstractBackground 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.