Amineptine

Abstract

Rosacea fulminans is characterized by the sudden onset of large, coalescing nodules and draining sinuses on the face. A few reports have linked medications to this condition, but none have described the onset of rosacea fulminans with pegylated interferon or ribavirin therapy. We report a patient who presented with rosacea fulminans after initiation of therapy for Hepatitis C.

Case Report

A 61-year-old Caucasian female with history of hepatitis C, hypertension, and rosacea was referred by her gastroenterologist for a facial eruption. She had a distant history rosacea that had been well controlled without therapy. One month prior to evaluation, she experienced an abrupt eruption of confluent red nodules and inflamed papules and plaques at her cheeks, chin, and forehead (Figures 1, 2). One week prior to this flare, she had begun therapy with pegylated interferon and ribavirin for treatment of' her chronic liver disease. Based upon her clinical presentation a diagnosis of rosacea fulminans was made. Therapeutic options were discussed including systemic antibiotics, topical steroids, oral prednisone, and isotretinoin. Systemic steroids were contraindicated due to her history of hepatitis C.

[FIGURE 1-2 OMITTED]

Isotretinoin was offered to the patient but she refused: instead we initiated treatment with doxycycline and metronidazole gel. She has yet to follow up in clinic for further evaluation of her condition and treatment effect. The temporal relationship between our patient's initiation of therapy and her cutaneous flare suggest the combination of therapy with interferon alpha and ribavirin were the contributing factors in exacerbation of her disease.

Discussion

Rosacea fulminans was originally described as 'pyoderma faciale' in 1940 by Drs. O'Leary and Kierland (1). Through their review of over 1600 cases of ache in women, they described a unique subset of patients: young women in their twenties and thirties with sudden onset of coalescing nodular and confluent draining sinuses on the face. Unable to isolate a particular cause, they attributed the inflammatory process to an infection of the sebaceous glands and follicular structures of the skin.

In 1992 Plewig et al. (2) redefined the condition and its nosology, relating the disease as a variant of rosacea, not acne. They suggested renaming the condition rosacea fulminans, analogous to the corresponding term, acne fulminans, which they defined for a similar disease in acne patients (34). Unlike acne fulminans, a condition occurring in young men consisting of sudden eruption of hemorrhagic ulcerations on the face, neck, chest, and back, rosacea fulminans more often affects young to middle-aged women and is comprised of deep nodules and fluctuating abscesses occurring solely on the face. Rosacea fulminans is not usually accompanied by systemic symptoms, but patients may experience low fever, fatigue, malaise, and/or weight loss.

The etiology of rosacea fulminans is unknown; however, various contributing factors have been described. Patients may have a history of ache and/or a propensity toward flushing and blushing. Patients have related the onset of disease with a recent history of trauma or emotional experience such as pregnancy or relocation (3-5). Rare case reports associate medications such as amineptine and high doses of vitamin B with eruption of this condition (6,7).

Laboratory studies may include mild elevations in white blood cell count and/or elevated erythrocyte sedimentation rate. Cultures are not consistently positive, yet studies have identified staphylococcus epidermidis, propoionibacterium acnes, and staphylococcus aureus as pathogens. Biopsies of lesions show extensive perifollicular, polymorphous inflammation with necrosis and subsequent degeneration of the pilosebaceous apparatus. Isolated and confluent abscesses are seen in more developed lesions. Significant numbers of eosinophils may be present as well (5). The course of disease usually peaks a few weeks or months after onset. Despite attempts at treatment, the condition tends to persist approximately one year, after which it usually regresses spontaneously.

Various treatment modalities have been used to aid with this difficult condition. Oral and topical antibiotics, benzoyl peroxide, ultraviolet B, intralesional and topical steroids, and isotretinoin have been used in treatment of this disease. Current recommendations include oral corticosteroids to aid with suppression of the inflammation and the subsequent addition of low dose isotretinoin (8). Warm compresses and topical corticosteroids may be beneficial in addition to medical therapy.

A variety of cutaneous reactions have been reported with interferon alpha and ribavirin. Most common occurrences with this combination of therapy include injection site reactions, lichenoid dermatitis, eczema, malar erythema, localized cutaneous necrosis, and bullous drug eruption. There are no reports in the literature of rosacea fulminans occurring during treatment with pegylated interferon alpha-2b and ribavirin.

Summary

Our patient had a history of rosacea with sudden onset of severe flare of her condition, with confluent red papules, plaques, and nodules localized at her face. She had recently begun a new treatment for her hepatitis C with combination pegylated interferon and ribavirin. The temporal relationship between our patient's initiation of therapy and her cutaneous eruption render the combination of therapy with pegylated interferon and ribavirin as the most likely trigger of her disease. While a number of anecdotal cases describing medication-induced rosacea fulminans have been reported, this combination of therapy has not been documented in the literature. We report this case of pegylated interferon alpha-2b and ribavirin therapy-induced rosacea fulminans.

References

(1.) O'Leary PA, Kierland RR. Pyoderma faciale. Arch Dermatol Syphilol 1940; 41:451-462.

(2.) Plewig G, Jansen T, Kligman AM. Pyoderma Faciale: A review and report of twenty additional cases: Is it rosacea? Arch Dermatol 1992; 128:1611-1617.

(3.) Plewig G, Kligman AM. Acne: Morphogenesis and treatment. Springer-Verlag NY Inc. New York, 1975; 196-199.

(4.) Plewig G, Kligman AM. Akne: Pathogenese, Morphologie, Therapie. Springer-Verlag NY Inc, New York, 1978: 208-212.

(5.) Massa MC, Daniel Su SP. Pyoderma faciale: A clinical study of twenty-nine patients. Journal of the American Academy of Dermatology 1982; 6:84-91.

(6.) Jeanmougin M, Civatte J, Cavelier-Balloy B. Rosaceous drug eruption caused by amineptine (Survector). Annales de Dermatologie et de Venereologie 1988; 115:1185-6.

(7.) Jansen T, Romitis R, Kreuter A, Altmeyer P. Rosacea fulminans triggered by high-dose vitamins B6 and B12. Journal of European Academy of Dermatology and Venereology 2001; 15:484-5.

(8.) Plewig G. Rosacea. In Dermatology in General Medicine. New York, McGraw Hill, Inc., 1993.

ADDRESS FOR CORRESPONDENCE:

Sarah Jensen MD

Department of Dermatology

Saint Louis University Health Sciences Center

1402 South Grand Boulevard

Saint Louis, MO 63104

T: 314-419-4280

COPYRIGHT 2003 Journal of Drugs in Dermatology
COPYRIGHT 2003 Gale Group