Follicular mucinosis successfully treated with isotretinoin

ARTICLE

In 1957, Pinkus used the term "alopecia mucinosa" for six cases histologically characterized by the mucinous degeneration of the hair follicles [1]. Follicular mucinosis (FM) was later suggested as a better term since the accumulation of acid mucopolysaccharides in the outer root sheath of the hair follicle is a common histological feature while the clinical presentation is variable and alopecia is not always evident [2]. The clinical lesions consist of grouped follicular papules and erythematous, nodular plaques with loss of terminal hairs.

A primary FM [3, 4] can be distinguished from a secondary form that is associated with cutaneous lymphoma [5, 6] or, rarely, with other skin diseases [7, 8]. The primary FM consists of two different clinical subgroups: one acute, characterized by erythematous papules and plaques, prominent follicles, and shedding of terminal hair localized to the head, neck and shoulders, and one, more chronic, in which the lesions are numerous, widespread and can persist for several years without development of an associated disorder [3, 4].

An effective standard therapy for FM is unknown. Corticosteroids, dapsone, mepacrimine, interferons and superficial X-ray have been used with variable results in individual cases [1, 9-11].

We report a case of localized FM which was dramatically improved by isotretinoin. To the best of our knowledge, the benefits of this drug in the treatment of FM have not been reported previously.

Case report

A 33-year-old Caucasian male was seen for a 2 month history of painless skin lesions on his forehead. Physical examination revealed grouped follicular papules, slightly infiltrated erythematous plaques and two red-violaceous nodules (Fig. 1A). He had been previously treated with systemic (tetracycline, erythromycin, amoxicillin) and topical (gentamycin, aureomycin) antibiotic therapy without any significant improvement.

On admission no superficial adenopathy was found, liver and kidney were of normal size and the patient was otherwise in excellent health. The laboratory tests were within normal limits. In particular, the blood count was: WBC 7.12 10^9/l with a differential count of 57.1% neutrophils, 1.8% eosinophils, 0.8% basophils, 33.9% lymphocytes, 6.5% monocytes.

Histology of a skin biopsy from a nodular lesion was not diagnostic since it showed an inflammatory lymphocytic infiltrate, admixed with several eosinophils, located around the vessels and the pilosebaceous structures in the dermis. Based on these findings, intralesional corticosteroid therapy was administered. Since no modification of the skin lesions was seen within 7 days, a second biopsy was performed. A conspicuous dermal infiltrate composed of lymphocytes, histiocytes and eosinophils surrounded and invaded the pilo-sebaceous structures that showed mucinous degeneration (Fig. 2A, B).

The presence of mucin was confirmed by positive staining with alcian blue (Fig. 2C).

Mycosis fungoides was excluded since atypical lymphocytes and epidermotropism were completely absent.

Treatment with isotretinoin at a dose of 0.5/mg/kg/day was started. A clinical improvement was noted after two weeks and a complete remission was achieved in two months (Fig. 1B). Isotretinoin was continued at the same dose for three weeks after healing and then progressively tapered. Treatment was definitively stopped four months after the first administration.

At the time of writing (about 3 years after the initial diagnosis) the patient had undergone clinical controls every six months in order to detect any relapse of FM and to exclude the development of any other FM-associated lymphoproliferative disorder.

Discussion

The treatment of FM has not been defined in the literature. Systemic or locally applied steroids, dapsone, mepacrimine, X-ray, interferons have been used in isolated cases [1, 9-11]. In our patient, isotretinoin led to a dramatic improvement of the skin lesions within two weeks without any relevant side effects.

There is no previous report of the use of isotretinoin in FM. In the absence of an established therapy, and because our patient did not respond to antibiotics and corticosteroids, we began treatment with this drug. To further support our therapeutic approach there is the evidence of improvement of mycosis fungoides-associated FM with isotretinoin [12]. At the time of our observation, the patient did not present any evidence of concomitant mycosis fungoides but it is well known that a cutaneous T-cell lymphoma can occur several years after the diagnosis of FM [3, 4].

Isotretinoin has proved effective in the treatment of other hair follicle dermatoses such as dissecting cellulitis and eosinophilic pustular folliculitis, but in our case the histology and the blood eosinophils count excluded these diagnoses [13].

FM is characterized by the accumulation of mucinous material in the epithelial hair follicle sheath and in the sebaceous glands [14]. It has been hypothesized that this phenomenon is induced by cytokines released by T lymphocytes of the infiltrate [15]. In the routine histological studies, in fact, the inflammatory infiltrate of FM is mainly composed of lymphocytes and macrophages [3, 4]. It is not known whether the mucin production is the initial event or a nonspecific pathological reaction pattern of the pilo-sebaceous structures [8]. The effects of isotretinoin on cellular proliferation and differentiation and on sebosuppression are well known; it has also been demonstrated that this drug is able to modulate a number of inflammatory and immunomediate events, particularly cell-mediated cytotoxicity [16, 17]. The efficacy in FM could be mediated by regulatory effect of isotretinoin on the infiltrate cells and/or by a modulation of the target organ (skin) response to the same cells. In our opinion isotretinoin seems to be of great interest in the treatment of FM; further studies should confirm this and make it possible to define its exact mechanism of action.

REFERENCES

1. Pinkus H, Macaulay WL, Lund HZ, et al. Alopecia mucinosa. Arch Dermatol 1957; 76: 419-24.

2. Jablonska S, Chorzelski T, Lanzucki J. Mucinosis follicularis. Hautarzt 1959; 10: 27-33.

3. Emmerson RW. Follicular mucinosis: a study of 47 patients. Br J Dermatol 1969; 81: 395-413.

4. Gibson LE, Muller SA, Leiferman KM, et al. Follicular mucinosis: clinical and histopathologic study. J Am Acad Dermatol 1989; 20: 441-6.

5. Mehregan AD, Gibson EL, Muller AS. Follicular mucinosis: histopathologic review of 33 cases. Mayo Clin Proc 1991; 66: 387-90.

6. Benchikhi H, Wechsler J, Rethers L, et al. Cutaneous B-cell lymphoma associated with follicular mucinosis. J Am Acad Dermatol 1995; 33: 673-5.

7. Cabrè J, Korting GW. Zum symptomatishen charakter der mucinosis follicolaris: ihr vorkommen beim lupus erythematodes chronicus. Dermatol Wochenschr 1964; 149: 513-8.

8. Wolff H, Kinney J, Ackermann AB. Angiolymphoid hyperplasia with follicular mucinosis. Arch Dermatol 1978; 114: 229-32.

9. Kubba RK, Stewart TW. Follicular mucinosis responding to dapsone. Br J Dermatol 1974; 91: 217-20.

10. Sonnex TS, Ryan TJ, Dawber RPR. Atypical follicular mucinosis controlled with mepacrimine. Br J Dermatol 1981; 105: 83-4.

11. Meissner K, Weyer U, Kowalzick L, Altenhof J. Successful treatment of primary progressive follicular mucinosis with interferons. J Am Acad Dermatol 1991; 24: 848-50.

12. Warrell RPJ, Coonley CJ, Kempin SJ, et al. Isotretinoin in cutaneous
T-cell lymphoma. Lancet 1983; 10: 629.

13. Berbis P, Jancovici E, Lebreuil G, et al. Eosinophilic pustolar folliculitis (Ofuji's disease): efficacy of isotretinoin. Dermatologica 1989; 179: 214-6.

14. Rongioletti F, Rebora A. Les mucinoses cutanées. Presse Med 1996; 25: 631-6.

15. Sabourin JC, Wechsler J, Bagot M, et al. Le mucinose folliculaire: entité dermatologique fréquemment associée à un lymphome T. Ann Pathol 1993; 13: 29-31.

16. Lotan R, Dennert G. Stimulatory effects of vitamin A analogues on induction of cell mediated cytotoxicity in vivo. Cancer Res 1979; 39: 55-8.

17. Mariguchi S, Jackson JC, Watson RR. In vitro effects of retinoids on human lymphocyte functions. Hum Toxicol 1985; 4: 365-78.

18. Haber H. Follicular mucinosis. Br J Dermatol 1961; 73: 313-22.