Guidelines for clinical trials of frontal fibrosing alopecia: consensus recommendations from the International FFA Cooperative Group (IFFACG).

BACKGROUND: Frontal fibrosing alopecia (FFA) has become one of the most common causes of cicatricial alopecia worldwide. However, there is a lack of clear aetiology and robust clinical trial evidence for the efficacy and safety of agents currently used for treatment. OBJECTIVES: To enable data to be collected worldwide on FFA using common criteria and assessment methods. METHODS: A multicentre, international group of experts in hair loss was convened by email to create consensus recommendations for clinical trials. Consensus was defined at > 90% agreement on each recommended part of these guidelines. RESULTS: Standardized diagnostic criteria, severity rating, staging, and investigator and patient assessment of scalp hair loss and other clinical features of FFA were created. CONCLUSIONS: These guidelines should allow the collection of reliable aggregate data on FFA and advance efforts in both clinical and basic research to close knowledge gaps in this condition.

Final results of a multicenter phase II study of the purine nucleoside phosphorylase (PNP) inhibitor forodesine in patients with advanced cutaneous T-cell lymphomas (CTCL) (Mycosis fungoides and Sézary syndrome).

BACKGROUND: Forodesine is a potent inhibitor of purine nucleoside phosphorylase (PNP) that leads to intracellular accumulation of deoxyguanosine triphosphate (dGTP) in T and B cells, resulting in apoptosis. Forodesine has demonstrated impressive antitumor activity in early phase clinical trials in cutaneous T-cell lymphoma (CTCL). PATIENTS AND METHODS: In this phase II study, patients with CTCL who had already failed three or more systemic therapies were recruited. We investigated the response rate, safety and tolerability of oral forodesine treatment in subjects with cutaneous manifestations of CTCL, stages IB, IIA, IIB, III and IVA. The safety population encompassing all stages was used for analysis of accountability, demographics and safety. The efficacy population differed from the safety population by exclusion of stage IB and IIA patients. RESULTS: All 144 patients had performance status 0-2. The median duration of CTCL from diagnosis was 53 months (5-516 months). The median number of pretreatments was 4 (range: 3-15). No complete remissions were observed. In the efficacy group of patients, 11% achieved partial remission and 50% had stable disease. The median time to response was 56 days and the median duration of response was 191 days. A total of 96% of all treated patients reported one or more adverse events (AEs) and 33% reported a serious AE. The majority of AEs were classified as mild or moderate in severity. The most commonly reported AEs (>10%) were peripheral edema, fatigue, insomnia, pruritus, diarrhea, headache and nausea. Overall eight patients died during the study: five due to sepsis and infections, one due to a second malignancy (esophageal cancer), one due to disease progression and one due to liver failure. CONCLUSION: Oral forodesine at a dose of 200 mg daily is feasible and shows partial efficacy in this highly selected CTCL population and some durable responses.

Central scalp alopecia photographic scale in African American women.

Central centrifugal cicatricial alopecia (CCCA) is a common but poorly understood cause of hair loss in African American women. A photographic scale was developed that captures the pattern and severity of the central hair loss seen with CCCA in order to help identify this problem in the general community and to potentially correlate clinical data with hair loss. The utility and reproducibility of this photographic scale was determined in a group of 150 African American women gathered for a health and beauty day who were evaluated by both four investigators experienced in the diagnosis of hair disorders and by the subjects themselves.

The role for interleukin-12 therapy of cutaneous T cell lymphoma.

Recent phase I and phase II trials using recombinant human interleukin-12 (rhIL-12) for cutaneous T cell lymphoma (CTCL) have been completed. Observations on 32 evaluable patients revealed an overall response rate approaching 50 percent. Biopsy of regressing lesions revealed an increase in numbers of CD8+ and/or TIA-1+ T cells. These results suggest that rhIL-12 may induce lesion regression by augmenting antitumor cytotoxic T cell responses. Future trials will be focused on strategies for further immune enhancement by the concomitant use of additional immune augmenting cytokines with rhIL-12.

A phase III, randomized, double-blind, placebo-controlled study of peldesine (BCX-34) cream as topical therapy for cutaneous T-cell lymphoma.

BACKGROUND: The purine nucleoside phosphorylase inhibitor peldesine is a new agent being evaluated as a T-cell inhibitor. OBJECTIVE: We attempted to determine the efficacy of peldesine (BCX-34) in a 1% dermal cream formulation as a treatment for cutaneous T-cell lymphoma (CTCL). METHODS: Ninety patients with patch and plaque phase CTCL, histologically confirmed by a referee dermatopathologist, were enrolled in a randomized, double-blind, placebo-controlled study. BCX-34 dermal cream 1% or the vehicle cream (as a placebo control) was applied twice daily to the entire skin surface for up to 24 weeks. Efficacy of the topical therapy was assessed in terms of complete or partial (> or = 50%) clearing of patches and plaques. RESULTS: Of the 89 patients able to be examined, 43 received BCX-34 and 46 received the placebo vehicle cream. One patient withdrew early and was not analyzed. The two groups were well balanced for potential prognostic factors. A total of 28% (12/43) of the patients treated with BCX-34 showed a response, but 24% (11/46) of patients who received vehicle also responded (P =.677). CONCLUSION: Although BCX-34 dermal cream 1% was not significantly better than the control as therapy for patch and plaque-phase CTCL, this appears to be the first published placebo-controlled trial evaluating treatment for CTCL. Whether the vehicle cream has more than a placebo therapeutic effect is unclear. The relatively high (24%) placebo response rate should be kept in mind in assessing other treatments for early-stage CTCL.

Lack of efficacy of finasteride in postmenopausal women with androgenetic alopecia.

BACKGROUND: Finasteride, an inhibitor of type 2 5alpha-reductase, decreases serum and scalp dihydrotestosterone (DHT) by inhibiting conversion of testosterone to DHT and has been shown to be effective in men with androgenetic alopecia (AGA). The effects of finasteride in women with AGA have not been evaluated. OBJECTIVE: The purpose of this study was to evaluate the efficacy of finasteride in postmenopausal women with AGA. METHODS: In this 1-year, double-blind, placebo-controlled, randomized, multicenter trial, 137 postmenopausal women (41-60 years of age) with AGA received finasteride 1 mg/day or placebo. Efficacy was evaluated by scalp hair counts, patient and investigator assessments, assessment of global photographs by a blinded expert panel, and histologic analysis of scalp biopsy specimens. RESULTS: After 1 year of therapy, there was no significant difference in the change in hair count between the finasteride and placebo groups. Both treatment groups had significant decreases in hair count in the frontal/parietal (anterior/mid) scalp during the 1-year study period. Similarly, patient, investigator, and photographic assessments as well as scalp biopsy analysis did not demonstrate any improvement in slowing hair thinning, increasing hair growth, or improving the appearance of the hair in finasteride-treated subjects compared with the placebo group. Finasteride was generally well tolerated. CONCLUSION: In postmenopausal women with AGA, finasteride 1 mg/day taken for 12 months did not not increase hair growth or slow the progression of hair thinning.

Pityriasis amiantacea: a report of two cases in adults.

Pityriasis amiantacea is a scaly condition of the scalp that is usually seen in children. It is most often associated with an underlying primary dermatosis. We describe two adult patients who did not present with concomitant scalp or cutaneous diseases.

Methods of hair removal.

The methods of hair removal vary between simple inexpensive means of home treatment (shaving, plucking, depilatories) to expensive and potentially time-consuming means used by paraprofessionals, nurses, and/or physicians (electrolysis, lasers, x-ray). The ways in which these different methods induce hair removal, the duration of such removal, and the nuances between devices within the same category of methods are discussed.

The presence of loose anagen hairs obtained by hair pull in the normal population.

To help determine the specificity of "loose anagen" (LA) hairs in Loose Anagen Syndrome, the presence or absence of LA hairs on a gentle but firm hair pull was evaluated in 110 normal subjects from a 0.5 to 83 y old. In children < or =10 y old, 61% had LA hairs on hair pull evaluation and 73% of all hairs obtained were LA hairs. In contrast, LA hairs were found in only two of 87 (2%) normal postpubescent subjects. The number of LA hairs was small in normal children (1-2 per hair pull) and a maximum of one out of every 6-7 hair pulls in adults, far less than that reported with Loose Anagen Syndrome. Although the mere presence of LA hairs on a hair pull test is thus not specific for LAS in children, the number per hair pull may have diagnostic significance. Correlation of these findings with the various hair disorder phenotypes currently termed Loose Anagen Syndrome will be important.

Finasteride in the treatment of men with androgenetic alopecia. Finasteride Male Pattern Hair Loss Study Group.

BACKGROUND: Androgenetic alopecia (male pattern hair loss) is caused by androgen-dependent miniaturization of scalp hair follicles, with scalp dihydrotestosterone (DHT) implicated as a contributing cause. Finasteride, an inhibitor of type II 5alpha-reductase, decreases serum and scalp DHT by inhibiting conversion of testosterone to DHT. OBJECTIVE: Our purpose was to determine whether finasteride treatment leads to clinical improvement in men with male pattern hair loss. METHODS: In two 1-year trials, 1553 men (18 to 41 years of age) with male pattern hair loss received oral finasteride 1 mg/d or placebo, and 1215 men continued in blinded extension studies for a second year. Efficacy was evaluated by scalp hair counts, patient and investigator assessments, and review of photographs by an expert panel. RESULTS: Finasteride treatment improved scalp hair by all evaluation techniques at 1 and 2 years (P < .001 vs placebo, all comparisons). Clinically significant increases in hair count (baseline = 876 hairs), measured in a 1-inch diameter circular area (5.1 cm2) of balding vertex scalp, were observed with finasteride treatment (107 and 138 hairs vs placebo at 1 and 2 years, respectively; P < .001). Treatment with placebo resulted in progressive hair loss. Patients' self-assessment demonstrated that finasteride treatment slowed hair loss, increased hair growth, and improved appearance of hair. These improvements were corroborated by investigator assessments and assessments of photographs. Adverse effects were minimal. CONCLUSION: In men with male pattern hair loss, finasteride 1 mg/d slowed the progression of hair loss and increased hair growth in clinical trials over 2 years.

Tretinoin emollient cream for photodamaged skin: results of 48-week, multicenter, double-blind studies.

BACKGROUND: The ability of topical tretinoin to improve certain signs of skin photodamage has been shown previously. OBJECTIVE: Our purpose was to assess the effectiveness of tretinoin emollient cream in maintaining or further improving photodamaged skin during extended use. METHODS: Photodamaged subjects who completed 24 weeks of once-daily use of tretinoin emollient cream 0.05% (n = 149) or 0.01% (n = 149) continued to use the same strength formulation in a 24-week double-blind extension. RESULTS: Maintenance of improvement or continued reduction in signs of photodamage was noted in both investigators' and subjects' evaluations of the 0.05% and 0.01% preparations; these results were confirmed by skin replica analyses. Cutaneous side effects were less common during the extension study than during the first 24 weeks of therapy. CONCLUSION: Both strengths of tretinoin emollient cream (0.05% and 0.01%) appeared safe and effective in the treatment of photodamaged skin during a 48-week treatment period.

Sustained improvement in photodamaged skin with reduced tretinoin emollient cream treatment regimen: effect of once-weekly and three-times-weekly applications.

BACKGROUND: Previous studies have documented reversal of long-term photodamage with once-daily applications of topical tretinoin. OBJECTIVE: Our purpose was to assess the effectiveness of tretinoin emollient cream in maintaining improvement in photodamage with a reduced frequency of applications. METHODS: A total of 126 subjects who completed 48 weeks of once-daily treatment with tretinoin emollient cream 0.05% were enrolled for an additional 24 weeks of tretinoin once weekly, three times weekly, or no therapy. RESULTS: The clinical improvement observed during 48 weeks of once-daily treatment was sustained with three-times weekly applications and to a lesser extent with once-weekly dosing, whereas effects tended to regress in subjects off therapy. The overall incidence of adverse events in the skin and subcutaneous tissues appeared to vary with dose frequency. CONCLUSION: After 48 weeks of once-daily treatment, the continued use of tretinoin emollient cream 0.05% at a dose of three times per week maintains and, in some cases, may further enhance improvement in photodamage. Discontinuation of therapy results in some reversal of beneficial effects.

Pentostatin (2'-deoxycoformycin) in the treatment of cutaneous T-cell lymphoma.

BACKGROUND: The treatment of patients with advanced or therapy-refractory cutaneous T-cell lymphoma (CTCL) remains a challenge. Pentostatin is a potent inhibitor of adenosine deaminase and is selectively toxic to lymphocytes. In a small number of patients with CTCL, it previously has been shown to be effective. OBJECTIVE: Our purpose was to evaluate the efficacy and safety of pentostatin in the treatment of patients with advanced and/or therapy-refractory CTCL. METHODS: Eighteen patients with stage I to IVb CTCL were treated with 4 to 5 mg/m2 of intravenous pentostatin every 1 to 4 weeks. RESULTS: Two patients (11%) had complete responses of 4 months and 6 years, respectively. These patients had stage III and IVa CTCL and had previously received many different external or systemic treatments. Partial remission (50% to 99% clearing) lasting for 1.5 to 6 months occurred in five patients (28%) with stage IIa (n = 3), stage IIb, and stage IVa CTCL. These patients had received a median of three prior external or systemic treatments. No major side effects were observed, and bone marrow suppression was mild. CONCLUSION: Single-agent pentostatin in intravenous doses of 4 to 5 mg/m2 is an effective systemic treatment of CTCL (39% objective response rate) with little toxicity.

Eccrine gland infiltration by mycosis fungoides.

After identifying prominent eccrine infiltration by atypical lymphocytes in a biopsy of tumor stage mycosis fungoides (MF), we sought to determine the pattern of eccrine epithelial infiltration in MF. The frequency, intensity, and distribution of infiltration of eccrine gland structures, including acrosyringium, duct and coil epithelium, was studied by examining 71 biopsy specimens from 42 patients with MF in which eccrine structures were present. These were obtained from a retrospective review of pathologic specimens from Duke University Medical Center from 1992 and 1993. At least focal eccrine infiltration was noted in 23 of the 71 biopsy specimens (32%). Immunohistochemical confirmation of T-lymphocyte phenotype was performed in the 23 cases with positive reaction to antibodies CD3 and CD45RO and negative reaction with CD20. Folliculosebaceous units were present in 22 of the 71 biopsy specimens and were at least focally involved by MF in 11 (50%) in this series. A control group of biopsy specimens of reactive dermatoses were characterized by more superficial location of lymphocytes, with more spongiosis and epithelial degenerative changes. These findings further illustrate the epitheliotropic behavior of MF.

Efficacy and safety of fluticasone propionate 0.005% ointment in the treatment of psoriasis.

Two multicenter, double-blind, randomized, vehicle-controlled parallel-group trials involving 388 patients were conducted to compare the efficacy and safety of fluticasone propionate 0.005% ointment to those of its vehicle in the treatment of moderate-to-severe psoriasis. The study medication (up to 100 gm/week) was applied topically to the affected target areas of the body twice daily for up to four consecutive weeks. Efficacy and safety were evaluated after one, two, three, and four weeks of treatment. In both studies, fluticasone ointment was clearly shown to be superior to vehicle throughout the four weeks of treatment. At the end of the treatment period, the superiority of fluticasone ointment was statistically significant for all efficacy measures. At the end of study 1, the skin of ten of eighty-eight patients (11%) who received fluticasone were rated as cleared by the investigators and fifty (57%) were rated as excellent or good. Of those who received vehicle, the skin of one of ninety (1%) was rated cleared and twenty-five (28%) were rated excellent or good. In study 2, the skin of three of 105 (3%) patients who received fluticasone were rated as cleared and sixty-nine (66%) were rated as excellent or good at the end of the study. Of those who were treated with vehicle, no patient's skin was rated cleared and thirty of 100 (30%) were rated excellent or good. Adverse events were few and mild. The most common drug-related adverse events were burning and pruritus at the site of application, which occurred in 6% of both the fluticasone-treated patients and those who received vehicle. These findings support the conclusion that fluticasone, 0.005%, ointment is clinically superior to its vehicle in the treatment of psoriasis.

Interferon in the treatment of cutaneous T-cell lymphoma.

All of the recombinant interferons are active agents for the systemic treatment of mycosis fungoides and Sézary syndrome. The response rates are similar to those observed with systemic chemotherapy. There is no clear evidence that combining interferons with other systemic therapies increases the response rates. The combination of interferon with PUVA provides provocative results. The optimal role of interferons in the treatment of mycosis fungoides and Sézary's syndrome is undefined.

Abnormalities of circulating T-cell subpopulations in patients with cutaneous T-cell lymphoma: cutaneous lymphocyte-associated antigen expression on T cells correlates with extent of disease.

The recent characterization of the cutaneous lymphocyte-associated antigen (CLA) as a skin-selective homing receptor for skin-associated memory T cells has suggested a possible mechanism for the tropism demonstrated by the neoplastic T cells in cutaneous T-cell lymphoma (CTCL). In this study, we used five parameter flow cytometry to evaluate expression of CLA and the peripheral lymph node homing receptor L-selectin on circulating T cells in a series of patients with CTCL. Because CTCL cells were previously shown to be CD7-, we looked at expression of these receptors on the CD7- T-cell subset as well as on total T cells. Our results indicate that CTCL patients have increased levels of both CLA+ and CD7- cells in their peripheral blood and that these abnormalities are not seen in patients with other cutaneous disorders. The levels of the CLA-bearing subset correlated with extent of cutaneous but not lymph node disease. By contrast, the CD7- L-selectin+ subset correlated with peripheral lymph node involvement by CTCL. Only the CD7- L-selectin- subset correlated with the number of morphologically abnormal lymphocytes in the peripheral blood. The results support the hypothesis that expression of tissue-selective homing receptors contributes to the unique pattern of tissue involvement seen in patients with CTCL.