Juvenile hyaline fibromatosis in two siblings

ARTICLE

Auteur(s) : Zohreh Tehranchinia, Hoda Rahimi

Skin Research Center, Shahid Beheshti University, M.C. Shohada-e Tajrish Hospital, Shahrdari St, 1989934148, Tehran, Iran

A 2-year-old boy was referred to our clinic for papular eruptions on his face and neck which had been present since 6 months of age. His parents were first cousins and his elder brother, who had similar lesions, had died at the age of three. The patient was the result of a normal vaginal delivery with a birth weight of 3.2 kg. He had no problem until 6 months of age, when his parents noticed that he experienced some difficulties in moving his limbs. At the same time, a progressive, papular eruption developed on his face, buttocks, dorsum of the neck, and perianal region.

On examination he had multiple, pearly, grouped papules on the dorsum of the neck (figure 1A) and his face. Similarly there were several fleshy nodules and tumors in the perianal region and on his buttocks. There was severe gingival hyperplasia that partially occluded the teeth, making feeding difficult (figure 1B). Also, flexion contracture of both knee and elbow joints was observed. His hearing and eyesight were normal. Results of hematologic and biochemical evaluations and urinalysis were within normal ranges. Skeletal radiography showed joint contractures, but no osteolytic lesions.

Histopathological study of a biopsy specimen taken from one of the perianal lesions revealed a normal epidermis with homogenization of the papillary dermis by an amorphous, eosinophilic material, with telangiectatic vessels and plumped fibroblasts (figures 1C, D), confirming the clinical diagnosis of juvenile hyaline fibromatosis.

Juvenile hyaline fibromatosis (JHF) is a rare autosomal recessive disease with onset in infancy or early childhood. It is characterized by multiple nodules, tumors and pink, pearly papules mainly located on the head, back and extremities. Joint contractures, gingival hypertrophy and osteolytic bone lesions may accompany the skin lesions [1]. The skin and soft tissue lesions are often the first presenting features; however, in some patients such as our patient, joint manifestations may be initial [2]. The primary morbidity is a result of the joint contractures.

The histological findings of cutaneous lesions in JHF are characterized by the varying degrees of fibroblasts and amorphous hyaline ground substance in the extracellular spaces of the dermis and soft tissues [3]. The pattern of amorphous, hyaline material in the dermis and the degree of cellularity indicated the diagnosis of JHF in our case.

It has been postulated that JHF may be a disorder of collagen metabolism. Ultrastructurally, an apparent increase in the amount of collagen type VI might account for inflexible skin and the limitation of joint movement in JHF. However, there is no consistent defect of collagen, and many affected individuals have normal collagen profiles. Abnormalities in the biosynthesis of chondroitin sulfate and/or hyaluronic acid have been reported in some patients [4].

A similar condition, infantile systemic hyalinosis (ISH), is characterized by the above findings, with further involvement of the viscera (gastrointestinal, cardiac, hepatic, splenic, and thyroid) and an inevitably fatal outcome. Many postulate that JHF and ISH are the same conditions with differing penetrance and phenotypic expression, and suggest referring to both as “hyaline fibromatosis syndrome” [5].

There is no specific treatment for the hyalinoses. The recommended treatment for JHF is surgical removal of the lesions, but local recurrences are common. There is a limited response to intralesional steroid injection in the early stages. Capsulotomy, corticosteroids, adrenocorticotropic hormone (ACTH) and physiotherapy have produced some improvement in the treatment of the joint contractures and gingivectomy has been tried for the gingival hypertrophy. Therapeutic trials with dimethylsulfoxide, ketotifen, calcitriol, and D-penicillamine have been attempted in some cases [6].

Juvenile hyaline fibromatosis and ISH remain stigmatizing, incapacitating, and sometimes fatal disorders, with no satisfactory treatment. The discovery of the responsible mutations provides some hope for gene therapy in the future.

Acknowledgments

References

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3 Katagiri K, Takasaki S, Fujiwara S, et al. Purification and structural analysis of extracellular matrix of a skin tumor from a patient with juvenile hyaline fibromatosis. J Dermatol Sci 1996; 13: 37-48.

4 Glover MT, Lake BD, Atherton DJ. Infantile systemic hyalinosis: newly recognized disorder of collagen? Pediatrics 1991; 87: 228-34.

5 Nofal A, Sanad M, Assaf M, et al. Juvenile hyaline fibromatosis and infantile systemic hyalinosis: a unifying term and a proposed grading system. J Am Acad Dermatol 2009; 61: 695-700.

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