Indian Journal of Dermatology, Venereology and Leprology Medknow Publications on behalf of The Indian Association of Dermatologists, Venereologists and Leprologists (IADVL) ISSN: 0378-6323 EISSN: 0973-3922 Vol. 71, Num. 2, 2005, pp. 112-114

Indian Journal of Dermatology, Venereology, Leprology, Vol. 71, No. 2, March-April, 2005, pp. 112-114

Case Report

Hyper IgE syndrome: Report of two cases with moderate elevation of IgE

Muhammed K

Department of Dermatology and Venereology, Medical College, Kozhikode
Correspondence Address:Kunnummal House, Koroth School Road, Vadakara, Kozhikode - 673101, Kerala
drmuhammedk@rediffmail.com

Code Number: dv0535

ABSTRACT

INTRODUCTION

Hyperimmunoglobulin E syndrome with recurrent infections (HIES) or Job′s syndrome is a primary phagocytic disorder characterized by atopic-like dermatitis which first manifests during infancy,[1] ′cold′ soft tissue abscesses, recurrent pneumonias, pneumatoceles and craniofacial and skeletal abnormalities. In 1966, Davis, Schaller and Wedgwood first reported Job′s syndrome. The nomenclature is derived from the similarity of the condition to the Biblical Prophet Job ′who was afflicted with sore boils from the sole of his feet unto his crown.′[2] The first case from India was reported in 1994 by Pherwani et al.[3] In 2001, Pherwani and Madnani reported six patients with prominent cutaneous and respiratory features, but only one had familial involvement.[4]

An elevated IgE level (>2000 IU/ml) and peripheral eosinophilia are the most constant findings in this disorder. We report two girls with the disorder, whose IgE levels were only moderately elevated.

CASE REPORTS

Case 1

A 6-year-old girl born of non-consanguineous parentage and uneventful pregnancy was brought on several occasions with fever, severe impetiginous lesions and multiple abscesses that each time subsided with systemic antibiotics like cefadroxil. From early childhood onwards, there was a history of atopic-like eczema, an episode of lung abscess and empyema. No family members were affected.

The tip of the nose was fleshy and the inter-alar distance was increased, with a coarse facies. The scar of drainage of empyema was still present on the chest wall. There were also multiple scars on the face, trunk and limbs. No bony abnormalities were detected.

An X-ray chest showed fibrosis in the right midzone. She had peripheral eosinophilia and the serum IgE was raised (420 IU/ml). ELISA for HIV was negative.

Oral vitamin C was started 500 mg daily with reduction in the recurrence of infections. However, after two years she died following a prolonged respiratory infection.

Case 2

A 12-year-old girl born of a non-consanguineous marriage presented with multiple discrete and confluent erythematous scaly papules and plaques with follicular prominence over the face, trunk and limbs with accentuation in the retroauricular area. The rash had been treated with topical betamethasone dipropionate. The girl had been admitted previously in the pediatrics ward for the treatment of staphylococcal pneumonia.

She had a coarse facies with a fleshy tip of the nose and increased inter-alar distance. Multiple scars that had followed furuncles were present over the limbs and trunk. All fingernails and toenails showed discoloration, dystrophy, loss of cuticle and subungual hyperkeratosis. Two tender cystic swellings of size 10 x 6 cm were present in the left inguinal region above and below the inguinal ligaments. On incision and drainage these discharged thick creamy pus.

S. aureus sensitive to cloxacillin was grown from the discharged pus. Nail clippings showed dermatophyte hyphae. Blood investigations showed only eosinophilia with raised ESR. The serum IgE was raised (564 IU/ml). Blood ELISA for HIV was negative. A chest radiograph showed multiple pneumatoceles [Figure - 1].

Oral vitamin C 500 mg was started daily with reduced recurrence of infections but the eczema did not regress.

DISCUSSION

HIES is a rare multisystem primary phagocytic disorder that affects the dentition, skeleton, connective tissue and immune system. It is inherited as a single locus autosomal dominant trait with variable expressivity. Our two patients had typical features of HIES.[5],[6] There was no family history of a similar illness in our patients. HIES may be caused by the mutation of a single gene, mutation in different genes in different families or deletion of contiguous genes in a short chromosomal region.[5] The disease focus for HIES had been mapped to the proximal region of chromosome 4q.[7] Recently, an autosomal recessive variant has been described,[8] in which the IgE level is lower than reported earlier.[4],[6]

Usually IgE levels in HIES exceed 2000 IU/ml. However, IgE levels may decrease with age, may fall within the normal range (0.1-90 IU/ml) in about 20% of the cases,[1],[5] and do not correlate with disease severity.[5] IgE antistaphylococcal antibodies are common and are relatively specific for the syndrome.[1] Both the cases being reported here showed only moderate elevation in serum IgE levels, viz. 420 IU/ml in the first case and 564 IU/ml in the second case. This further supports the view that if other features of HIES are present, a normal IgE level should not exclude the presence of HIES in older children.[5]

Dermatitis is present in more than 80% of the patients of HIES and usually begins at 2 months to 2 years of age.[1] It resembles atopic dermatitis, but is accentuated in retroauricular and hairline areas in addition to flexural involvement.[1] The skin and soft tissue infections present as cellulitis, furunculosis, paronychia, suppurative adenitis and deep soft tissue ′cold′abscesses. Constitutional symptoms like fever may be absent or blunted. Severe pulmonary infections caused by either S. aureus or H. influenzae are common. Empyema may complicate pneumonia and there is a high propensity for bronchiectasis and pneumatoceles. Otitis externa, chronic otitis media, chronic mastoiditis, dental and periodontal diseases are common. Mucocutaneous candidiasis and tinea unguium are observed in HIES.[1]

Non-immunological features of HIES have been reviewed.[5] Failure or delay of shedding of primary teeth occurred in 72% of patients, recurrent bone fractures in 57%, joint hyperextensibility in 68% and scoliosis in 70%.[5]

Patients with HIES have a distinctive facial appearance that is independent of gender and race: coarse facies, palatal elevation, large nasal inter-alar distance and variably, craniosynostosis and macrocephaly. Patients may have facial asymmetry with hemihypertrophy, prominent forehead, deep set eyes, broad nasal bridge, wide fleshy nasal tip and mild prognathism.[5]

Treatment involves giving appropriate antibiotics for specific infections. In our patients, cefadroxil and cloxacillin were used, with drainage of abscesses. Intravenous immunoglobulins usually provide temporary relief. Methotrexate is very effective in some cases.[4] Other treatment options include levamisole, cimetidine, ascorbic acid, and transfer factor.[4] On vitamin C 500 mg daily, the recurrences of infection were less, but the eczema did not regress. Ascorbic acid has been reported to improve the chemotactic responsiveness of neutrophils from patients with recurrent infection and high IgE levels.[1],[9]

Primary phagocytic disorders like HIES are rare and usually first manifest during childhood. A phagocytic disorder should be considered in patients with unusually severe and recurrent infections by common pathogens. Patients usually die prematurely due to pulmonary infections. Early diagnosis of phagocytic disorders can be lifesaving and can lead to a significant reduction in morbidity.

REFERENCES

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