Long-term effects of total skin electron beam therapy for mycosis fungoides on hair and nail loss and regrowth.

OBJECTIVE: To better document the risk of permanent hair and nail loss after total skin electron beam therapy (TSEBT) for mycosis fungoides (MF). METHODS: Interviews and evaluations were conducted in 13 patients with MF treated with TSEBT alone and two patients treated with concomitant TSEBT and chemotherapy with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP). Evaluated parameters included time to hair and nail loss and regrowth, the density of hair regrowth, and quality of hair and nail regrowth. RESULTS: Most patients had complete loss of scalp hair during treatment, and new growth appeared about 2 months following treatment completion. After 18 months, most patients felt their hair had regrown to about 70% of baseline thickness without cosmetically obvious alopecia. The patients treated with TSEBT and concomitant chemotherapy had substantially less scalp hair regrowth with persistent cosmetically obvious alopecia. Some lost eyebrows and eyelashes, but complete or near-complete regrowth generally occurred. Most patients lost their nails following TSEBT, with complete regrowth noted by most patients 5 months after treatment. New nails were most often normal, but a few patients developed post-therapy nail dystrophies. CONCLUSION: This data can be used to better inform patients of likely long-term changes of hair and nails following TSEBT.

Atypical vascular lesions extending outside the radiation field: a diagnostic challenge.

Atypical vascular lesion (AVL) is an uncommon, benign vascular proliferation seen in previously irradiated skin, most commonly after radiotherapy for breast cancer. Atypical vascular lesion and angiosarcoma may share overlapping clinical and histopathologic features. We report the first case of AVL occurring outside the field of radiation. This patient's clinical course and histopathology was overall consistent with AVL, including two biopsies with focal MYC positivity. However, due to variations in the interpretation of her histopathology, the management plans devised by two centers involved in her care were widely discordant and she was treated with chemotherapy and extensive surgery for angiosarcoma. Great care must be taken to distinguish between these entities, as treatment for angiosarcoma may be associated with significant morbidity.

Primary cutaneous marginal zone lymphoma with subclinical cutaneous involvement and biclonality.

Primary cutaneous extranodal marginal zone lymphoma (MZL) of mucosa-associated lymphoid tissue (MALT) represents a monoclonal B-cell neoplasm that typically presents with papules, plaques or nodules. We describe a patient with a primary cutaneous MALT lymphoma with unusual clinical features and an unusual immunophenotype. Conventional microscopy together with immunohistochemistry and in-situ hybridization showed the presence of lymphoma in normal-appearing and minimally erythematous skin as well as in clinically involved skin. Furthermore, at least two distinct clones were shown, one of which had κ-light chain restriction, and the other of which had λ-light chain restriction. This case represents a newly described clinical appearance of primary cutaneous MZL and shows that some patients may have more than one neoplastic clone.

Standards for genital protection in phototherapy units.

BACKGROUND: Phototherapy is a useful therapy for many dermatologic disorders and is known for its low side-effect profile. However, one potential notable side effect is genital skin cancer. Unfortunately, no standards for genital protection currently exist for this preventable complication. Patients treated with phototherapy may already have a decreased quality of life because of their primary dermatologic disorder. Development of squamous cell carcinoma of the genitalia may certainly further affect the quality of life. OBJECTIVE: The objective was to determine which readily available materials afford the best photoprotection of the male genitalia. METHODS: Seven common materials used in phototherapy units for genital protection were placed over ultraviolet (UV) B and UVA monitors and placed in broadband UVB, narrowband UVB, and UVA full-body units. The percentage of light blocked was then calculated. RESULTS: Blue and white cotton underwear, blue surgical towels, an athletic supporter with or without a cup, and the psoralen plus UVA pouch provided acceptable means of genital protection; however, surgical masks did not. LIMITATIONS: Only the most commonly used materials were tested in the phototherapy units. The materials were not of a single material type or similar masses. In addition, only one of each type of full-body phototherapy unit was used to obtain the data. CONCLUSION: Although a polyester composition provides better UV protection, factors such as low porosity and higher mass are intrinsic to decreasing the amount of UV penetration of any fabric. Of the commonly used objects, surgical masks do not provide sufficient protection to the genital area.

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.

Hydrocortisone butyrate 0.1% lotion in the treatment of atopic dermatitis in pediatric subjects.

BACKGROUND: Hydrocortisone butyrate (HCB) is currently marketed as a cream, ointment, and solution. A new lotion formulation of hydrocortisone butyrate 0.1% (Locoid lotion) has been developed and evaluated. OBJECTIVE: The objective of this study was to evaluate the efficacy and safety of HCB 0.1% lotion compared to the vehicle in subjects aged 3 months to less than 18 years with mild to moderate atopic dermatitis (AD). METHODS: In this multicenter double-blind study, 284 subjects with mild to moderate AD were randomized 1:1 to receive HCB 0.1% lotion or the vehicle for a duration of 4 weeks. "Treatment success" was defined as those subjects with a final Physician Global Assessment (PGA) score of 0 or 1 that had at least a 2-point reduction in the PGA score from baseline to day 29. Safety was assessed by monitoring adverse events. RESULTS: Analyses of the final PGA score showed a significant treatment effect (P <.001) in favor of the HCB 0.1% lotion group. The safety profile of the HCB 0.1% lotion was also favorable. LIMITATIONS: The study did not assess the durability of the treatment effects (ie, safety and efficacy) after completion of the 4-week treatment period nor the potential need for longer term therapy given the chronic nature of AD. CONCLUSION: Results demonstrate the safety and efficacy of HCB 0.1% lotion in the treatment of mild to moderate AD in children 3 months to 18 years of age.

Intermittent therapy for flare prevention and long-term disease control in stabilized atopic dermatitis: a randomized comparison of 3-times-weekly applications of tacrolimus ointment versus vehicle.

BACKGROUND: Intermittent dosing of a topical calcineurin inhibitor for preventing atopic dermatitis (AD) disease relapse in patients with stabilized AD has not been evaluated. OBJECTIVE: We sought to evaluate the long-term efficacy and safety of 3-times-weekly use of tacrolimus ointment in preventing AD disease relapse. METHODS: Adult and pediatric patients with moderate to severe AD who were clear of disease after up to 16 weeks of treatment with tacrolimus ointment were randomized in a double-blind fashion to 3-times-weekly treatment with either tacrolimus ointment (0.03% or 0.1%) or vehicle for 40 weeks. The primary end point was the number of flare-free treatment days. RESULTS: A total of 125 patients were randomized to tacrolimus and 72 patients to vehicle. The mean number of flare-free treatment days was 177 for tacrolimus and 134 for vehicle (P = .003). Median time to first relapse was 169 days for tacrolimus and 43 for vehicle (P = .037). LIMITATIONS: Generalizability to all patients seen in clinic may be limited because only patients who responded to tacrolimus ointment in the stabilization phase were randomized into the maintenance phase of the trial. CONCLUSIONS: Maintenance therapy with tacrolimus ointment was associated with significantly more flare-free days compared with vehicle, and a significantly longer time until first disease relapse.

Adult patients with moderate atopic dermatitis: tacrolimus ointment versus pimecrolimus cream.

The objective of this study was to compare the efficacy and safety of tacrolimus ointment and pimecrolimus cream in adults with moderate atopic dermatitis (AD). A randomized, investigator-blinded, 6-week, multicenter study enrolled patients (> or =16 years) with mild to very severe AD. Patients with moderate AD at baseline were analyzed. At study completion, tacrolimus ointment-treated patients had significantly greater improvement in Eczema Area Severity Index score compared with pimecrolimus cream-treated patients (59% versus. 43% reduction, respectively; P=.01). Significantly more tacrolimus ointment-treated patients than pimecrolimus cream-treated patients improved by 1 or more grades on the Investigators' Global Atopic Dermatitis Assessment (P<.02). A total of 5 pimecrolimus cream-treated patients discontinued the study early due to lack of efficacy compared with no tacrolimus ointment-treated patients (P=.02). Overall, reported adverse events occurred at a similar frequency for both treatment groups. Tacrolimus ointment is more effective than pimecrolimus cream in the management of adults with moderate AD.

Methotrexate-induced cutaneous ulceration in patients with erythrodermic mycosis fungoides.

Methotrexate-induced cutaneous ulceration has rarely been reported in patients with mycosis fungoides. We report 4 patients with mycosis fungoides who developed cutaneous ulceration as an initial manifestation of methotrexate toxicity. Methotrexate dose at the time of ulceration ranged from 10-60 mg. All 4 patients were erythrodermic, which may have predisposed them to this toxic effect. It is important to recognize cutaneous ulceration as an uncommon, but potentially serious, side effect of methotrexate in these patients, and to differentiate it from ulceration due to progressive lymphoma.

Phase II clinical trial of bexarotene gel 1% in psoriasis.

We report the results of a nonrandomized, open-label pilot trial investigating the safety, tolerability, and efficacy of bexarotene gel 1% in treating chronic mild to moderate plaque psoriasis. Twenty-four adults with mild to moderate stable plaque psoriasis involving 15% or less of their body surface were enrolled. Patients applied bexarotene gel 1%, using an application frequency escalation regimen, starting at once every other day and increasing to 4 times daily as tolerated and beneficial for up to 24 weeks. The primary efficacy instrument was a Physician's Global Assessment (PGA) score evaluating the overall response to treatment. This utilized individual signs of psoriasis and the percent of body surface area involvement. Safety assessments included physical examinations, recording of adverse events, and laboratory safety evaluations. Fifteen out of 24 enrolled patients (63%) achieved at least 50% improvement by PGA score at 2 or more consecutive visits, and 6 (24%) achieved clearing of 90% or more. Six patients maintained a response throughout 8 weeks of follow-up. An increased response appeared to correlate with a higher frequency of gel application. Adverse events occurred primarily at application sites and were mild or moderate in severity. Bexarotene gel 1% was active in treating mild to moderate plaque psoriasis with achievement of durable responses in some patients and was well-tolerated. A randomized, placebo-controlled study would be useful in confirming these results.

Tacrolimus ointment is more effective than pimecrolimus cream in adult patients with moderate to very severe atopic dermatitis.

OBJECTIVE: To compare the efficacy and safety of tacrolimus ointment 0.1% and pimecrolimus cream 1% in adult patients with moderate to very severe atopic dermatitis (AD). METHODS: A total of 281 patients (141 treated with tacrolimus and 140 treated with pimecrolimus) were randomized to a multicenter, investigator-blinded, 6-week study. RESULTS: Tacrolimus-treated patients had significantly greater improvements in the Eczema Area Severity Index score compared with pimecrolimus-treated patients (mean percent reduction from baseline to study end: 57% vs 39%, respectively; p=0.0002). Treatment success was also significantly greater among the tacrolimus-treated patients compared with pimecrolimus-treated patients (40% vs 22% at study end; p=0.001), as was the improvement in percentage of total body surface area affected (a reduction of 49% vs 34% at study end; p=0.01). Both treatment groups had similar improvements in patient assessment of itch. There were no significant differences in the incidences of adverse events, including application-site burning and application-site pruritus, the two most commonly reported adverse events. Significantly more pimecrolimus-treated patients than tacrolimus-treated patients withdrew from the study due to lack of efficacy (10 vs 1, p=0.005). CONCLUSION: Tacrolimus ointment is more effective than pimecrolimus cream in adults with moderate to very severe AD. Both agents have a similar safety profile.

Tacrolimus ointment 0.03% shows efficacy and safety in pediatric and adult patients with mild to moderate atopic dermatitis.

BACKGROUND/OBJECTIVE: Tacrolimus ointment is approved for the treatment of moderate to severe atopic dermatitis (AD). We sought to evaluate the efficacy and safety of tacrolimus ointment 0.03% compared with vehicle in the treatment of patients with mild to moderate AD. METHODS: Two identically designed, independent, randomized, double-blind, 6-week studies--one pediatric and one adult--in patients with mild to moderate AD were conducted. Combined data from 617 patients were used in the analysis. The primary efficacy end point was percentage of patients with treatment success (defined as "clear" or "almost clear" on the Investigator's Global AD Assessment) at end of study. RESULTS: As early as day 4, treatment success occurred in 17.7% of patients treated with tacrolimus compared with 9.8% of patients treated with vehicle ( P = .003), and by study end had increased to 49.7% for tacrolimus versus 29.0% for vehicle (P < .0001). Tacrolimus was associated with significantly less application site pruritus than vehicle (29.0% vs 37.5%; P = .03). There was no difference between tacrolimus and vehicle in the incidence of application site skin burning and stinging. CONCLUSION: Tacrolimus ointment 0.03% is effective and safe for the management of mild to moderate AD in both adult and pediatric patients, and has a rapid onset of action.

Clobetasol propionate 0.05% lotion in the treatment of moderate to severe atopic dermatitis: a randomized evaluation versus clobetasol propionate emollient cream.

Atopic dermatitis (AD) is a chronic inflammatory and pruritic skin disorder marked by alternating periods of relapse and remission. This multicenter, randomized, active- and vehicle-controlled, investigator-blinded study compared the efficacy and safety of clobetasol propionate lotion to clobetasol propionate cream formulation and lotion vehicle in the treatment of moderate to severe AD. A total of 229 subjects applied treatment twice-daily for 2 weeks. Clobetasol propionate lotion was significantly more effective than its lotion vehicle at 2 weeks and comparable to the cream formulation. Clinical success after a 2-week, treatment-free follow-up period was greater in the clobetasol propionate lotion group than in the cream group. Clobetasol propionate lotion is effective, safe, well tolerated and offers a better remission profile in the treatment of moderate to severe AD as compared to clobetasol propionate emollient cream.

Clobetasol propionate shampoo 0.05%: a new option to treat patients with moderate to severe scalp psoriasis.

Psoriasis is a chronic, papulosquamous condition that affects up to 2% of the U.S. population. Approximately 50% of patients with psoriasis have involvement of the scalp. This was a multicentre, randomized, vehicle-controlled, double-masked and parallel-group study. The aim was to evaluate the efficacy and safety of clobetasol propionate shampoo, 0.05% versus its corresponding vehicle in subjects aged 12 years and older with moderate to severe scalp psoriasis over a treatment period of 4 weeks. Recurrence of scalp psoriasis was assessed during a two week follow-up period. A total of 142 subjects were treated. Results after 4 weeks demonstrated that clobetasol propionate shampoo, 0.05% was with a similar safety profile significantly more effective than its vehicle. The novel short contact shampoo formulation of clobetasol propionate is convenient and efficacious and minimizes systemic exposure while being efficient, safe and well-tolerated in the treatment of moderate to severe scalp psoriasis.

Double-blind, randomized, vehicle-controlled clinical trial of once-daily benzoyl peroxide/clindamycin topical gel in the treatment of patients with moderate to severe rosacea.

BACKGROUND: Systemic antibiotics such as tetracycline are well accepted as effective in treating the inflammatory papular/pustular phase of rosacea but may be associated with systemic side-effects. Few controlled data on the use of topical antibiotics in rosacea are available. OBJECTIVE: We evaluated the efficacy and tolerability of a fixed combination of 5% benzoyl peroxide and 1% clindamycin in a topical gel for the treatment of rosacea. Methods This was a 12-week, double-blind, vehicle-controlled, randomized, prospective, parallel-group study in 53 patients with moderate to severe rosacea. RESULTS: The mean percentage reduction in papules and pustules from baseline to the end of treatment was 71.3% in the benzoyl peroxide/clindamycin group (n = 26) and 19.3% in the vehicle group (n = 26; P = 0.0056). A significant (P = 0.0141) difference in favor of benzoyl peroxide/clindamycin was evident by the third week of treatment. Severity scores for erythema, papules/pustules, and flushing/blushing decreased more with benzoyl peroxide/clindamycin than with vehicle. Overall rosacea severity, Physician Global Assessment, and Patient's Global Assessment at the end of treatment were all significantly improved with benzoyl peroxide/clindamycin compared with vehicle (P = 0.0101, 0.0026, and 0.0002, respectively). Application site reactions were reported in four patients (14.8%) in the benzoyl peroxide/clindamycin group. CONCLUSION: A once-daily topical application of a combination of 5% benzoyl peroxide and 1% clindamycin is effective and well tolerated in patients with moderate to severe rosacea.

Lymph node grading for staging of mycosis fungoides may benefit from examination of multiple excised lymph nodes.

BACKGROUND: Lymph node (LN) histopathologic class has been shown to be a significant determinant of survival in patients with mycosis fungoides. Often, histopathologic evaluation of just 1 node is used in staging patients with cutaneous T-cell lymphoma. OBJECTIVE: We examined whether sampling multiple nodes alters the staging and prognostic group placement of patients with mycosis fungoides as compared with sampling just 1 node. METHODS: Multiple LNs were obtained from a single, local region for histopathologic evaluation and grading in 8 patients with mycosis fungoides. RESULTS: Differences in histopathologic grading using multiple nodes were found in 5 of 8 patients. There was a potential upstaging of the assigned disease stage, compared with the stage that might have been assigned had just 1 node been sampled, in 3 patients. The differences in LN grading also potentially led to differences in prognostic group placement in 4 patients. CONCLUSION: Determining histopathologic grades from multiple LNs may allow a more accurate stage and prognosis to be assigned to patients.

Progression of cutaneous B-cell pseudolymphoma to cutaneous B-cell lymphoma.

BACKGROUND: Debates regarding nosology and clonality surround the entity known as cutaneous pseudolymphoma and its questionable transformation to frank cutaneous lymphoma. The relevance of these arguments is important, not only from a diagnostic standpoint, but also for making inferences based upon behavior, prognosis, and treatment. OBJECTIVE: Our goal was to demonstrate further evidence of progression from cutaneous pseudolymphoma to malignant lymphoma while at the same time advocating a comprehensive plan for evaluation, treatment, and followup of these patients. METHODS: A retrospective review was conducted of four patients initially considered to have cutaneous B-cell pseudolymphoma (CBPL) and who were later treated for primary cutaneous B-cell lymphoma (CBCL). A review of the literature of cases suggesting progression to malignant lymphoma from precursor lesions was also performed. RESULTS: Four patients initially diagnosed with CBPL by a combination of histologic, immunophenotypic, and gene rearrangement criteria had a progressive clinical course that, over a range of 17-51 months, evolved into CBCL. All patients had a comprehensive systemic workup to rule out the possibility of extracutaneous disease and were treated with local radiation therapy and close followup. There has been no evidence of extracutaneous disease with an average followup of 14 months. CONCLUSION: The potential for certain cutaneous pseudolymphomas to progress to CBCL is real. The combination of histologic and immunophenotypic criteria, along with the clinical picture, remains the best way to judge the aggressiveness of the lesion. Gene rearrangement studies, whether performed by Southern blot or polymerase chain reaction (PCR), are of limited value and should be used to support the overall clinicopathologic picture. Radiation therapy of these patients should be thought of early in the management plan and is a very successful form of treatment when combined with close followup.