|
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
Hyper IgE syndrome with recurrent infection (Job's syndrome) is a rare idiopathic primary immunodeficiency disease characterized by the triad of elevated serum IgE (>2000 IU/ml), recurrent cutaneous abscesses and recurrent sinopulmonary infections. The bacteria which commonly infect these patients are Staphylococcus aureus and Haemophilus influenzae. Therapy should include prolonged antibiotic therapy and early surgery. Non-specific agents like levamisole and ascorbic acid may reduce recurrent infections. We are reporting two girls, six and twelve years of age, presented with recurrent cutaneous and respiratory infections and moderately elevated levels of serum IgE.
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
1. | Paller AS. Cutaneous manifestations of Non-AIDS immunodeficiency. In: Moschella SL, Hurly HJ, editors. Dermatology. Philadelphia: WB Saunders company; 1992. p. 356-60. Back to cited text no. 1 |
2. | Donabedian H, Gallin JI. The Hyper immunoglobulin E recurrent Infection (Job's) syndrome. A review of the NIH experience and literature. Medicine 1983;62:195-208. Back to cited text no. 2 [PUBMED] |
3. | Pherwani AV, Rodrigues C, Dasgupta A, Bavadekar M, Rao ND. Hyper immunoglobulin E syndrome. Indian Pediatr 1994;31:328-30. Back to cited text no. 3 |
4. | Pherwani AV, Madnani NA. Hyper immunoglobulin E syndrome. Indian Pediatr 2001;38:1029-34. Back to cited text no. 4 [PUBMED] [FULLTEXT] |
5. | Grimbacher B, Holland SM, Gallin JI, Greenberg F, Hill SC, Malech HL, et al. Hyper IgE syndrome with recurrent infections-An autosomal dominant multisystem disorder. N Engl J Med 1999;340:692-702. Back to cited text no. 5 [PUBMED] [FULLTEXT] |
6. | Salaria M, Singh S, Kumar L. Hyper Immunoglobulin E syndrome. Indian Peditr 1997;34:827-9. Back to cited text no. 6 [PUBMED] |
7. | Segal BH, Holland SM. Primary phagocytic disorder of childhood. Pediatr Clin North Am 2000;47:1311-38. Back to cited text no. 7 [PUBMED] |
8. | Renner ED, Puck JM, Holland SM, Schmitt M, Weiss M, Frosch M, et al. Autosonomal recessive hyperimmunoglobulin E syndrome: A distinct disease entity. J Pediatr 2004;144:93-9. Back to cited text no. 8 |
9. | Friedenberg WR, Marx JJ Jr, Hansen RL, Haselly RC. Hyper immunoglobulin E syndrome: Response to transfer factor and ascorbic acid therapy. Clin immunol immunopathol 1979;12:132-42. Back to cited text no. 9 |
Copyright 2005 - Indian Journal of Dermatology, Venereology, Leprology
The following images related to this document are available:
Photo images
[dv05035f1.jpg]
|