Familial nevoid sebaceous gland hyperplasia affecting three generations of a family

ARTICLE

Familial nevoid sebaceous gland hyperplasia has rarely been described in the literature [1-5]. It mainly affects males with sudden onset at puberty and a slow but continuous progression over the years. It presents with soft, confluent, yellow papules predominantly involving the forehead, the cheeks and the chin. The neck, column and parts of the upper thorax may also be affected. Characteristically, the periorbital, perinasal, preauricular and perioral regions are spared. In most cases, it is accompanied by severe seborrhea of the skin. Typically, acneiform lesions are missing. Patients mostly have normal serum androgen levels. Dermatohistopathology typically shows sebaceous gland hyperplasia only with microcomedo formation without P. acnes colonization and without any signs of inflammation [3]. Differential diagnosis reveals premature sebaceous gland hyperplasia [6, 7], naevus sebaceus, adenoma sebaceum and epithelioma adenoides cysticum (Brooke). The pedigree of all reported cases, including ours, suggests autosomal dominant inheritance with incomplete penetrance.

Case report

Case 1

A 54-year-old man developed seborrhea and multiple yellow papules on the face and on the upper chest around puberty. He remembered that his mother and sister had similar skin lesions. On first admission the face was characterized by severe seborrhea and multiple yellowish papules predominantly involving the forehead, the cheeks and the chin (Fig. 1A). He was treated with isotretinoin 0.5 mg/kg body weight per day over 6 weeks, then reducing to 0.2 mg/kg body weight/d. Seborrhea and the skin texture improved markedly (Fig. 1B). Isotretinoin was then reduced to a dose of 10 mg twice daily. Further lowering of the dose led to a relapse. He has now been taking isotretinoin continuously 2 x 10 mg/d without any side-effects for 2 years.

Case 2

The 25-year-old son of patient 1 developed skin symptoms at the age of 16 years (Fig. 2). Various topical acne therapies had not led to any improvement in his condition. He showed severe seborrhea and multiple, aggregated papules on the face and the upper thorax and, to a very mild degree, on the upper back. With isotretinoin 0.5 mg/kg/d for 3 weeks the skin greatly improved. Isotretinoin was then reduced to 3 x 20 weekly for another 3 weeks. The patient is now on isotretinoin 2 x 20 mg per week without any relapse or side-effect.

Case 3

The 44-year-old niece of patient 1 and cousin of patient 2 (Fig. 2) had been suffering from her early puberty from severe seborrhea and skin lesions which appeared as rather aggregated yellow-brownish papules predominantly involving the forehead and the cheeks (Fig. 3A). She was also put on isotretinoin 0.5 mg/kg/d for 3 weeks which was then reduced to 0.3 mg/kg/d for another 3 weeks. At the same time she started antiandrogenic contraception with cyproteronacetate plus ethinylestradiol (Diane 35^®). She is now on isotretinoin 2 x 10 mg per day with a great benefit (Fig. 3B).

Case 4

The 25-year-old daughter of patient 3 (Fig. 2) had been treated topically for acne for a long time before she presented to our department. She had mild seborrhea but also multiple papules on the face and the thorax. She was treated with isotretinoin 0.5 mg/kg/d for 4 weeks and subsequently 2 x 10 mg daily with led to a great improvement. Because of planned pregnancy she interrupted isotretinoin for 20 months. As she noticed an increase of seborrhea and skin lesions after delivery of a healthy baby she started to take isotretinoin 3 x 10 mg/d again and subsequently 2 x 10 mg/d which immediately reduced the seborrhea and improved the skin texture.

Discussion

Dupre et al. were the first to describe two brothers who were affected by familial sebaceous hyperplasia of the face in 1980 [1]. In 1983, Graham-Brown et al. reported on a papular plaque-like eruption of the face due to nevoid gland hyperplasia in a female without hyperseborrhea. We described the third family including a mother and her daughter affected by nevoid sebaceous gland hyperplasia [3]. The most recent reports were from Thailand with affected patients over 5 generations [4] and from Spain with 3 patients over 2 generations [5]. Our family represents important further evidence of this rare disease as it affects 3 generations including 4 (5?) patients which is the largest family but one (4). According to reports from the family, the mother of patient 3 is also most likely affected but due to severe medical problems she was not able to present to our department. The case of De Villez et al. differs from the other reports as this patient showed a nevoid premature sebaceous gland hyperplasia with papulo-nodular lesions also involving the perioral region as well as inflammatory acneiform lesions [6]. The case reported by Burton et al. does not contribute to familial sebaceous gland hyperplasia as they describe a patient with premature sebaceous gland hyperplasia who was on immunosuppressive medication due to a kidney transplant [7]. In those reports also describing the treatment, all patients were successfully treated with oral isotretinoin [3-5, 7] which is the therapy of choice. According to our experience, isotretinoin should initially be given at a dose of >= 0.5 mg/kg body weight per day for a minimum of 3 weeks. In females, antiandrogen contraception such as cyproteroneacetate or chlormadinonacetate should be started accompanied by isotretinoin application at intervals such as 3 times per week. As antiandrogen therapy is not possible in men, the continuous isotretinoin application has to be prolonged in a daily modus and can then be tapered down to a maintenance interval regimen. Further investigation is needed to decide whether dermabrasion and chemical peelings may be of additional benefit. From our experience of the two women reported by us in 1987, antiandrogen therapy with cyproteronacetate 2 mg plus ethinylestradiol 0.035 mg was not sufficient to reduce the sebaceous hyperplasia of > 50%, which was only possible with isotretinoin. It should be emphasized that further investigation has to be done on the androgen receptor density and activity in the sebocytes and on the follicular keratinocytes as well, in this type of sebaceous gland disease.

We want to emphasize that familial nevoid sebaceous gland hyperplasia is still often misdiagnosed as seborrhea with widened follicular openings or acne and that an appropriate family history and examination of family members is necessary if this unusual diagnosis is suspected.

REFERENCES

1. Dupre A, Bonafé JL, Lamon R. Functional familial sebaceous hyperplasia of the face. Clin Exp Dermatol 1980; 5: 203-7.

2. Graham-Brown RAC, McGibbon DH, Sarkany I. A papular plaque-like eruption of the face due to naevoid sebaceous gland hyperplasia. Clin Exp Dermatol 1983; 8: 379-82.

3. Gollnick H, Orfanos CE. Familial nevoid sebaceous hyperplasia with hyperandrogenism. Clinical Dermatology, The CMD Case Collection. World Congress of Dermatology, Berlin, May 24-29 1987, Schattauer Verlag, 350-2.

4. Boonchai W, Leenutaphong V. Familial presenile sebaceous gland hyperplasia. J Am Acad Dermatol 1997; 36: 120-2.

5. Grimalt R, Ferrando J, Mascaro JM. Premature familial sebaceous hyperplasia: successful response to oral isotretinoin in three patients. J Am Acad Dermatol 1997; 37: 996-8.

6. De Villez RL, Roberts LC. Premature sebaceous gland hyperplasia. J Am Acad Dermatol 1982; 6: 933-5.

7. Burton CS, Sawchuk WS. Premature sebaceous gland hyperplasia: successful treatment with isotretinoin. J Am Acad Dermatol 1985; 12: 182-4.