a case report of juvenile hyaline fibromatosis

CASE REPORTA case report of juvenile hyaline fibromatosis Department of Dermatology, King Abdulaziz University Hospital, Jeddah, Saudi Arabia Received 14 April 2014; revised 6 May 2014; a

CASE REPORT

A case report of juvenile hyaline fibromatosis

Department of Dermatology, King Abdulaziz University Hospital, Jeddah, Saudi Arabia

Received 14 April 2014; revised 6 May 2014; accepted 12 June 2014

KEYWORDS

Juvenile;

Hyaline;

Fibromatosis;

Autosomal;

Recessive

Abstract Juvenile hyaline fibromatosis (JHF) is a rare, autosomal recessive disease characterized

by early onset papulonodular skin lesions, soft tissue masses, joint contractures, gingival hypertro-phy, stunted growth and osteolytic bone lesions Histopathological examination of the cutaneous lesions is unique and characterized by an accumulation of an amorphous, hyaline material in the dermis with increased number of fibroblasts Herein, we report an 11 year-old girl who presented with papulonodular lesions on the scalp, chin, ears, elbows, knees, back and perianal skin She had gingival hypertrophy and contractures of the elbows, hips, knees and ankles

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1 Introduction

Juvenile hyaline fibromatosis (JHF) is a rare autosomal

reces-sive disease with an onset in infancy or early childhood (Yayli

et al., 2006) Less than 70 cases have been reported worldwide

(Park et al., 2010; Uslu et al., 2007) It is characterized by

pap-ulonodular skin lesions, gingival hyperplasia, joint

contrac-tures and bone lesions (Ribeiro et al., 2009) 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

tis-sues (Tehranchinia and Rahimi, 2010) The etiology of JHF is

still unknown but capillary morphogenesis protein 2 and

muta-tion in a gene on chromosome 4q21 are considered to be

caus-ative factors (Altug et al., 2009; Karacal et al., 2005; Thomas

et al., 2004)

2 Case report

An 11-year-old girl presented with multiple asymptomatic skin lesions at different body sites She was a product of a full term normal pregnancy for a third-degree consanguineous parents Other family members (parents, one brother and three sisters) are healthy except for her older brother who is affected by the same disease She was well till the second month of age when her mother started to notice difficulties in moving her limbs with progressive painless contractures At the age of two, the first skin lesion appeared in the perianal area which was com-plicated by painful defecation At the age of three, difficulty in feeding developed as a result of progressive swelling of the gums that almost covered her teeth Multiple skin lesions appeared on the face and digits along with swellings on the scalp, back, elbows and knees at the age of 6 and increased gradually in number and size Apart from skin lesions, joint contractures and her failure to thrive, there were no systemic symptoms and the patient was otherwise healthy with normal mental function They sought medical advice many times but accurate diagnosis has not been made

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Skin examination showed whitish-pinkish papules and

nod-ules on the chin, ears, digits (Figs 1–3), and perianal region

and multiple skin colored tumors on the scalp, back, elbows

and knees, largest measuring 10· 4 cm (Figs 4–7) Oral

exam-ination revealed extensive gingival hyperplasia (Fig 8) Joint

contractures were evident in the wrists, hips, knees and ankles

(Fig 9)

Skeletal radiographs showed joint contractures and

osteo-lytic bone lesions (Fig 10) Routine laboratory tests showed

normal results except for iron deficiency anemia

Histopathol-ogical examination with hematoxylin–eosin stain showed

der-mal deposits of eosinophilic hyaline material with increased

fibroblasts (Figs 11 and 12) Based on the characteristic

clini-cal and histopathologiclini-cal findings, a diagnosis of JHF was

made

3 Discussion

Juvenile hyaline fibromatosis (JHF) was originally described

by Murray in 1873 under the name ‘‘molluscum fibrosum’’

(Denadai et al., 2012) At that time, it was considered a variant

of neurofibromatosis Whitfield and Robinson later reported

two more cases in 1903 and suggested the disease be

recatego-rized as multiple fibromata, but it was not until 1972 when this

condition was given the current name of juvenile hyaline

fibro-matosis by Kitano et al Thomas et al (2004), Lim et al

(2005), Slimani et al (2011) An autosomally recessive mode

of inheritance is accepted, but sporadic cases can occur

Figure 1 Pearly papules over the chin

Figure 2 Whitish–pinkish papules and nodules involving the

right ear

Figure 3 Right hand showing multiple pinkish nodules

Figure 4 Large subcutaneous tumor over the scalp

Figure 5 Large subcutaneous tumor over the right elbow

Figure 6 Large subcutaneous tumors over the back

(Yayli et al., 2006) The gene that causes JHF has been mapped

to 4q21 and mutations in the capillary morphogenesis (factor

-2 gene) have also been described (Altug et al., 2009; Karacal

et al., 2005; Thomas et al., 2004) The exact pathogenesis is unknown but several theories have been proposed, most attrib-uting JHF lesions either to aberrant synthesis of glycosamino-glycans by fibroblasts or to disordered collagen metabolism (Lim et al., 2005; Tzellos et al., 2009) (seeTable 1)

The disease is defined clinically by a constellation of find-ings including pearly skin papules or subcutaneous firm nod-ules, joint contractures, acralosteolytic lesions, gingival hypertrophy and normal intelligence (Yayli et al., 2006) Skin lesions can be polymorphous papules, small, rosy, clustered and located in the face and neck, particularly around the nos-trils, ears, paranasal folds and the chin along with nodular lesions or plaques on the scalp, limbs and perianal regions (Ribeiro et al., 2009) They are slow growing and painless and have a tendency to recur following excision (Krishnamurthy and Dalal, 2011) Gingival hyperplasia is a common finding that may be severe enough to interfere with feeding, and may result in poor oral hygiene, infection and dental caries (Nofal et al., 2009)

Musculoskeletal involvement in JHF is frequent, and flex-ion contracture of large joints is the most debilitating problem; most adolescents and adults become bedridden and die of infection (Slimani et al., 2011) It has been hypothesized that contractures result from infiltration of the capsules of the joints (S, 1992) Osteolytic bone lesions are commonly observed in the distal phalanges, skull, and long bones and

Figure 7 Large subcutaneous tumor over the right knee

Figure 8 Severe gingival hyperplasia

Figure 9 Flexion contractures of both hips, knees and ankle

joints

Figure 10 Right distal eccentric radial metaphyseal lytic lesion

Figure 11 Low power histopathological image shows dermal deposits of eosinophilic hyaline material (Hematoxylin–eosin stain)

Figure 12 High power histopathological image shows numerous fibroblasts embedded in homogenous hyaline material (Hematoxylin–eosin stain)

they have the same histological features as the skin lesions

(Yayli et al., 2006) The skin and soft tissue lesions are often

the first signs of presentation; however, in other patients, joint

manifestations may be primary (Karacal et al., 2005)

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 condition with differing penetrance

and phenotypic expression (Thomas et al., 2004) Hyaline

fibromatosis syndrome (HFS) is a recently introduced term

to include both disorders This term was introduced because

of the many similarities between JHF and ISH, including

clin-ical features, histopathologclin-ical patterns, and the same gene

mutation (Raak SM, 2013)

The diagnosis of JHF can be confirmed by histology The

tumors are poorly circumscribed and consist of cords of

spin-dle-shaped cells embedded in a homogeneous eosinophilic

matrix They are often found in the dermis, subcutis and

gin-giva, although the bone and joints may also be involved

(Krishnamurthy and Dalal, 2011)

No specific treatment is available for JHF (Bharambe,

2012) The treatment is only esthetic and its aim is to limit

orthopedic disability (Krishnamurthy and Dalal, 2011) Early

surgical removal of skin lesions may help, but recurrences

are common (Tehranchinia and Rahimi, 2010; Quintal and

Jackson, 1985) Joint contractures may respond to

intralesion-al systemic steroid physiotherapy, capsulotomy and orintralesion-al

D-penicillamine (Denadai et al., 2012; Krishnamurthy and

Dalal, 2011; El-Maaytah et al., 2010) Gingivectomy can

improve the amount of oral intake, but when it is not enough

to recover patient’s nutritional deficiency, parenteral feeding

such as tube feeding, gastrostomy and placing a central line

should be considered (Park et al., 2010) Frequent visits for

periodontal treatment and maintenance of good oral hygiene

are important factors in decreasing the growth rate of the

gin-givae in patients with JHF (El-Maaytah et al., 2010) Genetic

counseling is of great importance as the recurrence risk is 25% in any future pregnancy

4 Conclusion JHF is a rare hereditary disease with progressive course that should be highly suspected in a patient with early onset papu-lonodules, joint contractures and gingival hypertrophy Early diagnosis and proper multidisciplinary management are crucial

in an attempt to slow the progression of this rare disabling disease

Funding The author did not receive financial support for this case report

Conflict of interest

We have no conflict of interest to declare

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