calcipotriene and Alopecia

Hair loss from cytotoxic drugs is classically ascribed to the loss of fractured hairs (anagen effluvium). Telogen hair loss has also been described but some authors have denied any effect on the hair cycle. There are conflicting reports on a protective effect of pretreatment with a vitamin D analogue on cytotoxic drug-induced hair loss in rodents.. To investigate the process of cytotoxic hair loss and any protective effect on the hair of pretreatment with topical calcipotriol.. Breast cancer patients who were about to receive cycles of chemotherapy with cyclophosphamide 600 mg m(-2), methotrexate 40 mg m(-2) and 5-fluorouracil 600 mg m(-2) were recruited and randomized to receive calcipotriol scalp solution 50 microg mL(-1) or vehicle. The solution was applied twice daily from 4 days prior to chemotherapy and continued for 14 days in each treatment cycle. Shed, plucked and cut hairs were sampled. Absolute shed rates, the proportion of major hair types, the presence of proximal hair shaft changes, regrowth (using the new anagen hair count) and hair density were assessed.. Ten patients receiving calcipotriol and 14 receiving vehicle completed three treatment cycles and nine from both groups completed six cycles. There was no detectable effect of calcipotriol on the proportion of patients experiencing minimal hair loss from chemotherapy, shed rates, plucked telogen and fractured hair counts, the morphology of shed and plucked hair, hair regrowth or hair density. Combining results of the treatment groups, there was a large variation in the impact of chemotherapy on hair loss, from total loss in five patients to no obvious loss in five. Excluding the latter, during chemotherapy shed telogen hairs (mean 81% of shed hairs) predominated over fractured (12%) and anagen hairs (6%) (P = 0.0002). The major pathological change was proximal hair shaft tapering, baseline mean 3% of shed hairs rising to 48% (P = 0.0005) during treatment, and there was a consequent decrease in normal telogen hairs, baseline mean 98% of all telogen hairs falling to 55% (P = 0.0005) during treatment. The pathological tapered telogen hairs had normal or small, sometimes diminutive, bulbs. Fracturing of hairs with diminutive bulbs produced typical 'exclamation mark' hairs.. The cardinal effects of cytotoxic drugs found in this study were tapering of the proximal hair shaft and premature entry of the follicle into telogen, conflicting with the conventional view that affected hair follicles continue in anagen. There was a resulting effluvium of a mixture of tapering telogen hairs and fractured hairs. As entry into telogen is an integral part of the process, cytotoxic hair loss may be regarded as a variant of the conventional 'telogen effluvium' and we propose the term 'atrophic telogen effluvium'. There was no obvious protective effect on the hair loss of prior treatment with topical calcipotriol.

Topics: Administration, Topical; Adult; Alopecia; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Calcitriol; Cyclophosphamide; Dermatologic Agents; Double-Blind Method; Female; Fluorouracil; Hair; Humans; Methotrexate; Middle Aged; Prospective Studies

Scalp psoriasis is associated with hair loss and an increased telogen/anagen ratio. Topical treatment of scalp psoriasis (with corticosteroids, dithranol or tar) results in decreased scaling, induration and erythema of the plaques. Calcipotriol is effective in the treatment of psoriasis vulgaris. However, the potent growth-inhibiting potential of this compound might theoretically induce hair loss. A study was designed to find out to what extent calcipotriol treatment modulates the percentage of anagen and telogen hair during treatment of scalp psoriasis. A group of 26 patients participated in a placebo-controlled dose-finding study on the efficacy of calcipotriol in scalp psoriasis. Hair plucks before and after treatment were taken. The telogen/anagen ratio remained unaffected during 6 weeks of calcipotriol treatment. No correlation was demonstrated between efficacy of treatment and quantification of telogen/anagen ratio. It can be concluded that the growth-inhibiting potential of calcipotriol is not reflected in the in vivo hair growth pattern during calcipotriol treatment.

Topics: Adult; Aged; Alopecia; Calcitriol; Dermatologic Agents; Dose-Response Relationship, Drug; Double-Blind Method; Female; Gels; Hair; Hair Follicle; Humans; Male; Middle Aged; Placebos; Psoriasis; Scalp Dermatoses

Chemotherapy-induced alopecia is thought to result from cytotoxic and apoptosis-related damage to the hair follicle. This study was designed to confirm whether keratinocyte apoptosis is indeed induced in growing (= anagen) hair follicles of C57 BL/6 mice after the injection of cyclophosphamide, using improved methods for histologic detection of apoptotic cells in murine skin. More importantly, we asked whether topical calcitriol-analogs are able to modulate cyclophosphamide-induced apoptosis in vivo, because there are conflicting reports on the effects of calcitriols on apoptosis in vitro. Anagen was induced in telogen mice on day 0 by depilation. Starting on day 5 post-depilation, the back skin of mice was topically treated with either 0.2 microg 1,25-dihydroxyvitamin D3, 2.0 microg calcipotriol, 0.02 microg KH 1060, or vehicle (ethanol) only. On the last day of treatment (i.e., day 9 post-depilation), all mice received 150 mg cyclophosphamide i.p. per kg as a single dose to induce alopecia, or vehicle (aqua dist.). Analysis of the treated skin by in situ-end labeling (using a modified terminal UTP nucleotide end labeling technique suitable for murine skin), by Hoechst 33342 stain, and by DNA electrophoresis on days 10 and 14, revealed the induction of massive apoptosis in cyclophosphamide-treated anagen hair bulbs, which was most prominent on day 10, whereas controls showed no follicular apoptosis. The calcitriol-pretreated groups demonstrated a significant reduction of apoptosis, with a maximal inhibition seen on day 14. This confirms that cyclophosphamide indeed induces massive keratinocyte apoptosis in anagen hair follicles, and provides evidence that topical calcitriol-analogs can suppress epithelial cell apoptosis in vivo. The mouse model employed here offers an excellent tool for dissecting the as yet poorly understood controls of keratinocyte apoptosis in situ and its pharmacologic manipulation.

Topics: Administration, Topical; Alopecia; Animals; Apoptosis; Calcitriol; Cyclophosphamide; Dermatologic Agents; Drug-Related Side Effects and Adverse Reactions; Female; Hair Follicle; Immunosuppressive Agents; In Situ Nick-End Labeling; Mice; Mice, Inbred C57BL

Topics: Alopecia; Anti-Bacterial Agents; Calcitriol; Dermatologic Agents; Humans; Scalp Dermatoses; Steroids