|Year : 2016 | Volume
| Issue : 1 | Page : 38-41
Juvenile hyaline fibromatosis or infantile systemic hyalinosis: Hyaline fibromatosis syndrome
K Amrutha Varshini1, K Haritha1, Chirag A Desai2, G Raghurama Rao1, A Prasad Chowdary1, A Amareswar3, P Ramana Murty1
1 Department of DVL, GSL Medical College, Rajhamundry, Andhra Pradesh, India
2 GSMC and KEM Hospital, Mumbai, Maharashtra, India
3 Surya Skin Care and Research Center, Visakhapatnam, Andhra Pradesh, India
|Date of Web Publication||4-Jan-2016|
G Raghurama Rao
Department of DVL, GSL Medical College, Rajanagaram, Rajahmundry - 533 296, Andhra Pradesh
Source of Support: None, Conflict of Interest: None
Juvenile hyaline fibromatosis or infantile systemic hyalinosis is a rare progressive, fatal autosomal recessive disorder characterized by widespread deposition of hyaline. Mutations in capillary morphogenesis gene 2 gene is responsible for both these conditions. They usually present with fleshy, papular lesions, joint contractures, gingival hyperplasia, and persistent diarrhea. We report a 1-year-old girl with typical facial lesions, joint contractures and mild gingival hyperplasia without history of diarrhea and recurrent infections. Skin biopsy revealed deposition of hyaline.
Keywords: Capillary morphogenesis gene 2 mutations, hyaline fibromatosis syndrome, infantile systemic hyalinosis, juvenile hyaline fibromatosis
|How to cite this article:|
Varshini K A, Haritha K, Desai CA, Rao G R, Chowdary A P, Amareswar A, Murty P R. Juvenile hyaline fibromatosis or infantile systemic hyalinosis: Hyaline fibromatosis syndrome. Indian J Paediatr Dermatol 2016;17:38-41
|How to cite this URL:|
Varshini K A, Haritha K, Desai CA, Rao G R, Chowdary A P, Amareswar A, Murty P R. Juvenile hyaline fibromatosis or infantile systemic hyalinosis: Hyaline fibromatosis syndrome. Indian J Paediatr Dermatol [serial online] 2016 [cited 2020 Jul 9];17:38-41. Available from: http://www.ijpd.in/text.asp?2016/17/1/38/173155
| Introduction|| |
Juvenile hyaline fibromatosis (JHF) and infantile systemic hyalinosis (ISH) are rare overlap allelic autosomal recessive disorders resulting from mutations in chromosome 4q21.21. They are clinically characterized by papulonodular skin lesions, joint contractures, gingival hypertrophy, perianal nodules, osteoporosis, bone fractures, recurrent infections, persistent diarrhea, and visceral involvement. The hallmark of this condition is deposition of amorphous hyaline material in various tissues. Both diseases present during infancy or in early childhood. The prognosis of ISH is very poor, and children do not survive more than 2 years.
| Case Report|| |
A 1-year-old female child, born out of third degree consanguineous marriage presented with multiple flesh-colored papular lesions over the nose, ears, gluteal cleft, and nodular lesions over the scalp with joint contractures of 6 months duration. At the time of birth, baby was well and weighed about 2 kg. At the age of 3 months, the parents noticed that the baby experienced discomfort on being handled and showed some difficulty in moving her limbs. Over the last 6 months, she gradually developed severe joint contractures in most of the large joints. Concomitantly, a progressive papular eruption developed on her nose, face, ears, scalp, and perianal regions. Her parents also noticed delayed milestones and delayed dentition. No other family members including her 6-year-old sibling were suffering from similar complaints. There was no history of diarrhea and recurrent infections. On clinical examination, she had multiple, pearly, pink, grouped papules of variable sizes over the bridge of the nose, nasolabial folds, perioral areas, and ears. Some of the papules coalesced to form thick plaques over the helix and concha of both ears. Three large nodules with central ulcerations were also present on her scalp [Figure 1]a and [Figure 1]b. Similarly, there were several fleshy papular and nodular lesions in the gluteal cleft and perianal region [Figure 2]. The skin was not thickened but showed hyperpigmented, subcutaneous plaques over the elbow joints and malleoli. She is not able to stand on her own due to painful contractures of elbows and knees [Figure 3]a and [Figure 3]b. Mild gingival hypertrophy with delayed dentition were also observed.
|Figure 1: (a) Pink, pearly, grouped papules on nose and paranasal areas, (b) nodular lesions with ulceration on scalp and thickening of ear|
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|Figure 3: (a) Hyperpigmented plaques over the elbow, (b) flexural contractures of both hands|
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Relevant hematological and biochemical studies revealed hemoglobin 7.3 g/dl, total leukocyte count 11,600, differential count P - 50%, L - 43%, E - 4%, M - 3%; erythrocyte sedimentation rate 20 mm/h, platelet count 8.3 lakhs/mm 3. Her lipid profile was total cholesterol 159 mg/dl, high-density lipoprotein 26 mg/dl, low-density lipoprotein (LDL) 111 mg/dl, very-LDL 22 mg/dl, and triglycerides 108 mg/dl. Liver function tests and thyroid profile were within normal limits. Radiographs of long bones and chest were normal. Abdominal ultrasound and magnetic resonance imaging brain were normal. Differential diagnosis of deposition disorders such as lipoid proteinosis and mucopolysaccharidoses were considered. Two biopsies were taken from the skin lesions of the scalp and gluteal regions. Both specimens revealed thickening of upper dermis without significant inflammatory infiltrate. The collagen appeared thickened, vertically oriented, and hyalinized with increased number of fibrocytes. The number of capillaries within this area was increased, dilated, and thick walled. The overlying epidermis was hyperplastic [Figure 4]a and [Figure 4]b. Deposits in the papillary dermis were periodic acid-Schiff positive. In view of clinical and histopathological findings, we arrived at the diagnosis of JHF.
|Figure 4: (a) Homogeneous, pale, and hyalinized papillary dermis and cellular proliferation composed of spindle and round cells (H and E, ×10), (b) hyalinization of papillary dermal collagen with fibroblast-like cells (H and E, ×40)|
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| Discussion|| |
As early as 1873, Murray had described a condition which he termed “molluscum fibrosum.” In 1972, Kitano et al. renamed the disorder “JHF.” Landing and Nadorra in 1986 described ISH in detail, apparently different from JHF. Similarly, number of earlier reports were of the opinion that these two conditions were distinct separate clinical conditions.,,, In 2003, Dowling et al. and Hanks et al. established that ISH and JHF are indeed part of a spectrum of the same disorder by identifying the capillary morphogenesis gene 2 (CMG2) that resides on chromosome 4q21. Mutations in the gene CMG2 that encodes capillary morphogenesis protein-2 are responsible for both disorders. Several studies, while distinguishing ISH and JHF, observed considerable overlap between the two conditions.,, It has been suggested that JHF and ISH exist within a continuum of disease with varying phenotypic expression and encompassing term “hyaline fibromatosis syndrome” has been proposed. Joint contractures, papular and nodular skin lesions, gingival hypertrophy, osteopenia, and normal brain development are clinical features of both ISH and JHF. Patients with ISH present within the first 6 months of life typically die of infection or diarrhea by 2 years of age while patients with JHF present late in infancy or childhood with milder symptoms usually live to the second or third decade. Common distinguishing features of ISH include thickened skin, erythema, or hyperpigmentation over bony prominences, visceral involvement, persistent diarrhea, frequent severe infections, and failure to thrive. Patients with JHF, on the other hand, tend to have larger nodules, commonly located on the scalp.,
Our case represents the overlap syndrome with features of both ISH and JHF with early onset of disease characteristic fleshy grouped papular lesions on the nose, ears, gluteal region, and larger nodular lesions over the scalp along with joint contractures. Till date, there has been no history of diarrhea, severe infection, or signs of visceral involvement. The child is under constant supervision to record the progress of her disease.
Differential diagnosis of hyaline fibromatosis syndrome includes congenital generalized fibromatosis, Farber lipogranulomatosis, lipoid proteinosis, mucopolysaccharidosis, Winchester syndrome. The pathogenesis of hyaline fibromatosis syndrome is not clear. It has been suggested that it may be due to an increased synthesis of glucosamine glycans by fibroblasts. Ultrastructurally an apparent increase in the amount of collagen Type VI might account for the clinical features of the firm, inflexible skin, and the limitations of joint movement in ISH.
The gene responsible for hyaline fibromatosis syndrome has been mapped to chromosome 4q21.21 and deletion mutations in CMG2/anthrax toxin receptor 2 has been documented in patients with both JHF and ISH. Thus, it has been said that both JHF and ISH are allelic, and they belong to the spectrum of the same disorder. CMG2 is an integrin-like cell surface receptor that binds laminins and Type IV collagen via a von Willebrand factor Type A domain and in the skin it is thought to play a role in cell-matrix interactions and basement membrane integrity and endothelial cell morphogenesis. Genotype-phenotype studies suggested that missense and other in-frame mutations that affect the cytoplasmic domain tend to cause JHF, whereas truncating mutations and missense mutations that affect the extracellular protein-binding domain tend to cause ISH. ISH and JHF are autosomal recessive with compound heterozygotes. In the majority of cases, consanguinity is an important feature. However, it is not an invariable finding and does not come in the way of diagnosis of ISH and JHF in the right clinical setting.
The prognosis of ISH is poor, and most treatments have not proven beneficial. Surgical excision of large tumors is recommended though recurrences are common. Oral D-penicillamine has been reported to improve joint mobility and flexibility in few cases. Gingival overgrowth may be treated with partial gingivectomy. Bacterial pneumonias and diarrhea cases need hospitalization for administration of parenteral antibiotics and to maintain fluid-electrolyte balance. Therapeutic trails with dimethyl sulfoxide, ketotifen, and calcitriol have been tried in individual cases.
After reviewing the literature and the presentation of our own case, we too believe that “hyaline fibromatosis syndrome” could be the appropriate common term for both ISH and JHF since no reliable distinction can be made between these conditions and overlapping cases exist.
Declaration of Patient Consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
We are highly thankful to Dr. Sandipan Dhar for solving our diagnostic dilemma by suggesting the diagnosis of “ISH.”
Financial Support and Sponsorship
Conflicts of Interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3], [Figure 4]