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.

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.

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.

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.

A double-blind controlled comparison of generic and trade-name topical steroids using the vasoconstriction assay.

Six generic formulations of five topical steroids were compared for bioequivalence with their trade-name counterparts using an in vivo vasoconstriction assay. Two of six generic formulations were found to show significantly less vasoconstriction than the respective trade-name topical steroids. The issue of generic equivalence of topical steroids is discussed, with particular emphasis on the vagaries of the vasoconstriction assay.

Systemic steroids with or without 2% topical minoxidil in the treatment of alopecia areata.

BACKGROUND AND DESIGN: Thirty-two patients with mild to extensive alopecia areata, including 16 patients with alopecia totalis or universalis, entered a randomized, controlled trial of a 6-week taper of prednisone followed by either 2% topical minoxidil or vehicle applied three times daily for an additional 14 weeks. The results of this study were compared with an open trial of 48 patients with alopecia areata treated with a similar taper of prednisone with concomitant 2% topical minoxidil applied twice daily. Only terminal hair growth was considered and was quantitated as 1% to 24%, 25% to 49%, 50% to 74%, and 75% to 100%: only those with more than 25% terminal hair regrowth were considered to have had an objective response. RESULTS: At the end of 6 weeks of prednisone, 47% (15/32) of patients had more than 25% regrowth, including nine of 20 patients who had had at least 75% hair loss at baseline. Side effects of prednisone were primarily weight gain and mood changes/emotional lability. At 3 months, six of seven minoxidil-treated patients vs one of six vehicle-treated patients who had an objective response to prednisone maintained or augmented this hair growth: at the 20-week visit, these numbers were three of seven and zero of four patients, respectively. In the open trial, objective hair growth with prednisone was 30%, related to the extent of hair loss at baseline, and this growth persisted in more than 50% of patients at 6 months with the use of 2% topical minoxidil. CONCLUSIONS: A 6-week taper of prednisone offers potential for more than 25% regrowth in 30% to 47% of patients with alopecia areata with predictable and transient side effects. Two percent topical minoxidil three times daily appears to help limit poststeroid hair loss.

Sweating in ectodermal dysplasia syndromes. A review.

Ectodermal dysplasia syndromes are currently classified based on constellations of clinical features, a major one of which is the presence or absence of normal sweating. The evaluation of sweating in these disorders has not been performed in a standardized manner, as is shown here in this literature review of a sampling of ectodermal dysplasia syndromes. Accurate evaluation of sweating is important not only in enabling more effective diagnosis and classification of patients with these syndromes, but also in aiding genetic counseling by potential detection of carrier states. A review of the variety of sweat tests currently in use is presented.

Topical minoxidil in the treatment of androgenetic alopecia in women.

Twenty-eight women with mild to moderate androgenetic alopecia were randomly assigned to apply either 2 percent topical minoxidil or placebo (vehicle) to their involved scalp areas twice daily. At the end of thirty-two weeks, there was a statistically significant increase of nonvellus target area hairs in the minoxidil-treated versus the vehicle-treated group (p = 0.006). Investigator assessment of moderate regrowth showed better results in subjects who used 2 percent topical minoxidil solution than those who used vehicle (p = 0.007), although subjects discerned no difference between treatment groups. Two percent topical minoxidil appears to be effective in the treatment of female androgenetic alopecia.

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.

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.

Letterer-Siwe disease in an adult.

Letterer-Siwe disease, a proliferative disorder of Langerhans' cells, usually affects children during the first year of life. A 67-year-old woman is described here whose initial manifestation was a characteristic skin eruption. The clinical, pathologic, and ultrastructural features of Letterer-Siwe disease are reviewed and their role in diagnosis discussed.

Alopecia: evaluation and management.

The patient presenting with hair loss may have a primary dermatologic disease, a genetically engineered process, an infectious disease, an underlying systemic illness, a drug reaction, or a psychological disorder. By first dividing the process into one of three categories, scarring, diffuse-nonscarring, or patchy-nonscarring, one then can approach the evaluation in a rational manner. Using the bedside techniques of a hair pull, hair pluck, and microscopic hair examination and directed laboratory tests, one can narrow the differential diagnosis and can recommend directed therapy.

The pharmacology of methotrexate.

Methotrexate is a useful antimetabolite for the treatment of both benign and malignant proliferative disorders. When the pharmacokinetics and potential toxicity of this drug are understood, treatment regimens can be tailored to the underlying kinetics of the target population. With the appropriate knowledge of the importance of urinary excretion of methotrexate and factors that influence this and with the ready availability of leucovorin, toxicity can be avoided in all but the most unusual of circumstances.

Human test models for bioequivalence of topical corticosteroids: a review.

It would be useful to have a safe, reliable, reproducible, and inexpensive human test model to determine the potency of topical corticosteroids and the bioequivalence of generic agents. Existing human test systems include erythema or inflammation induced by irritants or other stimuli, experimentally induced cutaneous disease-like states, and bioassays in patients with psoriasis. None of these systems is currently reliable enough to warrant general use. Among the shortcomings of existing test systems are the difficulty of producing a uniform, steroid-responsive test condition, the requirement to use occlusion in several of the systems, and the lack of agreement among the results of different tests. Despite these shortcomings, some of the tests may prove useful in comparing innovator and generic topical corticosteroids and in screening the potency of new agents.

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.

Erosion of psoriatic plaques after chronic methotrexate administration.

A 43-year-old white man developed a shallow erosion of a psoriatic plaque after chronic administration of methotrexate. This unusual cutaneous sign may be the first sign of methotrexate toxicity.

Topical clobetasol-17-propionate: review of its clinical efficacy and safety.

Clobetasol-17-propionate, the most potent of currently available topical steroids as predicted by the vasoconstrictor assay, has just been approved in the United States. In psoriasis, it has proved significantly more effective than class II steroids and as or more effective than the only marketed class I steroid. In the more steroid-responsive eczemas, the superior efficacy of clobetasol is also apparent, but less striking. Clobetasol prolongs remission rates, making intermittent treatment schedules feasible and minimizing inherent potential steroid side effects. Clobetasol may also be useful in the treatment of a myriad of other skin conditions. A review of the pharmacology, efficacy, and side effects of this addition to our dermatologic armamentarium is presented here.

Topical minoxidil in male pattern baldness: effects of discontinuation of treatment.

Ten men with male pattern baldness who had been treated with 2% or 3% minoxidil for at least 4 months were evaluated for any changes in scalp hair growth on and off drug. Objective assessments by hair counts showed a mean doubling of nonvellus target scalp hairs on topical minoxidil and loss of most of these recruited hairs when the drug was discontinued. Four of ten men had nonvellus hair counts off topical minoxidil that fell below baseline levels. Thus, hair growth on topical minoxidil is not sustained when the drug is discontinued.