© 2003 European Academy of Dermatology and Venereology

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CASE REPOR T

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Blackwell Publishing Ltd.

Job’s syndrome – a case report

S

Verma,†

U

Wollina‡*

†

University of Virginia, Penn State University Medical School, Hershey, and SUNY, Stony Brook, USA;

‡

Department of Dermatology, Hospital

Dresden-Friedrichstadt, Friedrichstrasse 41, D-01067 Dresden, Germany.

*

Corresponding author, Department of Dermatology Krankenhaus

Dresden-Friedrichstadt, Friedrichstrasse 41, Dresden 01067, Germany, tel.: +49 3514801685; fax: +49 3514801219; E-mail: Wollina-Uw@khdf.de

ABSTRACT

Job’s syndrome is a rare immune disorder characterized by atopic dermatitis-like skin lesions, elevatedserum IgE-levels, repeated occurrence of skin and respiratory tract infections, and skeletal abnormalities.We report on a 12-year-old boy with Job’s syndrome from Gujarat State, India. He disclosed the character-istic face, eczematous skin reactions and skin and lung infections. Long-term chemoprophylaxis was real-ized with oral penicillins that dramatically improved the course of his disease. Other treatment options arediscussed but not all meet the needs of developing countries.

Key words:

chemoprophylaxis, hyper–IgE syndromes, Job’s syndrome

Received: 21 January 2002, accepted 9 September 2002

Introduction

The spectrum of hyper–IgE syndrome includes atopic der-

matitis with excessive IgE levels and Job’s syndrome. Job’s syn-

drome is a rare disorder with an incidence of one in 500 000

and onset in early childhood. It is thought that mutations of

the interleukin-4 (IL-4) receptor play a role in a subset of

patients but the genetic background is only poorly under-

stood. It is assumed to represent a multiorgan disease with

inheritance as a single-locus autosomal dominant trait

with variable expression.

1,2

Characteristically those patients

develop increased IgE levels. They tend to decrease later on

but patients are unable to handle bacterial infections, in

particular staphylococcal infections, of skin and respir-

atory tract. Abscesses often occur without signs of systemic

inflammation.

1–3

Pulmonary manifestations include recur-

rent alveolar lung infections, pneumatoceles and, occasionally,

pneumothorax.

4

Delayed eruption of permanent teeth and

a reduced rate of absorption of primary teeth roots was

reported.

5,6

Recurrent fractures, hyperextensible joints and

scoliosis are frequent skeletal findings.

1,2

Facial abnormal-

ities including hyperteleorism with a flat and broad nose

and philtrum, coarse skin, deep set eyes, prognatism and

a thickened lower lip provide a recognizable face of Job’s

syndrome.

7

Studies on cytokine activities in Job’s syndrome do not pro-

vide a unique pattern. Patients with Job’s syndrome have been

reported to express more IL-12 in a recent study, while other

cytokines and chemokines such as ENA-78, MCP 3 and eotaxin

are underexpressed.

8

Other studies could not confirm an ele-

vated, but found a normal, IL-12 expression by various stimuli

except

Staphyloccocus aureus

, with which cells from Job’s

syndrome released markedly less interferon-

γ

(IFN-

γ

), which

could not be enhanced significantly by IL-12.

9–11

Patients

with Job’s syndrome had significantly increased production

of granulocyte-macrophage-colony stimulating factor (GMCSF)

by resting or stimulated mononuclear cells. The production

of reactive oxygen intermediates by neutrophils treated with

opsonized zymosan was found to be increased.

l

-selectin expres-

sion on quiescent and activated granulocytes and lymphocytes

was depressed.

12

Increased GMCSF may explain the reduced

l

-selectin expression, decreased chemotaxis and increased oxygen

radical production and tissue damage in this disease. Increased

IgE and IgG4 production was found to be partially corrected by

exogenous IL-12 and IFN-

γ

. The addition of antibodies against

the IL-4 receptor or soluble IL-4 receptor completely abolished

overproduction of IgE and IgG4.

13–15

The differential diagnoses of Job’s syndrome include atopic

dermatitis (in particular atopic dermatitis with excessive IgE),

Wiscott–Aldrich syndrome and Langerhans cell histiocytosis.

712

Verma and Wollina

© 2003 European Academy of Dermatology and Venereology

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, 711–714

We report on a case from Gujarat State, India.

Case report

A 12-year-old boy from a non-consanguinous marriage

was seen in November 2000. After a normal delivery, he was

treated with antituberculosis agents for suspected pulmonary

tuberculosis at the age of 7 months. The treatment was dis-

continued because of bloody stools. At the age of 18 months the

boy developed a severe upper respiratory tract infection that

was treated with antibiotics and tuberculostatics for 6 months.

At this time his chronic otitis media started and is evident to the

time of writing.

In 1993 he was diagnosed to have a lung abscess and was

given antibiotics for 4 months. Another course of tubercu-

lostatics was given. In 1994 he developed a left-sided inguinal

lymphnode enlargement with suppuration and abscess forma-

tion for which he was given another 6 months of antituberculosis

treatment. In 1996 he underwent a tonsillectomy because of

recurrent upper respiratory tract infections.

In November 2000 he started getting a severe itching with a

papular eruption on the trunk that resembled atopic dermatitis.

This was the first time we saw the boy and started topical ther-

apy for the eczema. On examination he showed facial abnor-

malities including hyperteleorism with a flat and broad nose

and philtrum, coarse skin, deep set eyes, prognatism and a

thickened lower lip. The ear lobes were low set (fig. 1a,b).

Numerous scars were found on the face, trunk and limbs

(fig. 2). He developed another lymphnode abscess in December

2000 that was treated with cefadroxil and topical mupirocin. He

also developed other abscesses on the proximal lower limbs that

were treated with oral antibiotics.

Upon investigations his IgE levels were grossly elevated and

showed fluctuation between 350 and 650 U/mL (normal range

3.6–81 U/mL). The eosinophils reached between 30% and 35%.

His haemoglobin was 10 mg/L.

Based on the combination of chronic dermatitis resembling

atopic dermatitis, relapsing severe bacterial infections of skin

and the respiratory tract, facial abnormalities and increased IgE

levels the diagnosis of Job’s syndrome was confirmed.

fig. 1 The face of Job’s syndrome: (a) hyperteleorism, broad philtrum and nose, deep set eyes and ear lobes, thickened lower lip; (b) eczematous skin lesions

with excoriations, papules and scaling.

Job’s syndrome

713

© 2003 European Academy of Dermatology and Venereology

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, 711–714

The patient was set under treatment with medium potency

topical steroids for the rash, penicillin V 400 mg/d as a prevent-

ive measure for skin and respiratory tract infections. The rash

and the otitis media go on unabated. He does get pyoderma-like

lesions once in a while but the abscesses stopped after starting

with penicillin. The treatment is well tolerated.

Discussion

Job’s syndrome is a multisystem disease characterized by

markedly elevated serum IgE, relapsing bacterial infections of

skin and respiratory tract, atopic dermatitis-like dermatosis

and skeletal abnormalities.

1,2

Its prognosis depends upon the

efficacy of anti-infectious measures since life-threatening

infections due to bacterial but also mycological and viral

infections are observed.

16–19

Another negative prognostic factor

is the possible development of B-cell neoplasias or leukaemia

due to chronic stimulation of immune cells by persistent

bacterial antigen presentation.

20–22

Different approaches to control bacterial infections and

improve immune functions have been reported, including

interferon-

α

and -

γ

and high-dose intravenous immunoglobu-

lin.

22–25

Bone marrow transplantation has failed to improve

Job’s syndrome in one case.

25

Despite the fact that interferons and

γ

-globulins are effective

they are not practical and affordable in many developing

countries. Therefore alternatives have to be found with a more

balanced cost–efficacy ratio. Long-term chemoprophylaxis has

been performed in single patients with Job’s syndrome using

oral sulfamethoxazole-trimethoprim therapy.

26,27

Another option

we used is oral penicillin, in particular penicillinase-resistant

penicillins that cover not only streptococci but staphylococci

including those strains that produce

β

-lactamase. Penicillins are

cheap, available in numerous countries from their own phar-

maceutical industry, and safe. In contrast to sulfamethoxazole

and trimethoprim that can cause severe drug reactions like Stevens

Johnson’s syndrome, photoallergic and phototoxic reactions,

photosensitivity is not a major problem for penicillins.

28

Despite the fact that chemoprophylaxis was not able to com-

pletely prevent any bacterial infection, the course of our patient

remarkably improved with oral penicillin therapy and severe

infections have not been observed.

fig. 2 Numerous scars after superficial and deep skin infections (a) and cold abscess formation (b) in Job’s syndrome.

714

Verma and Wollina

© 2003 European Academy of Dermatology and Venereology

JEADV

(2003)

17

, 711–714

Job’s syndrome is not a common disease but should be con-

sidered in individual cases where a resistant atopic dermatitis is

accompanied by skin and airway infections. Medical history,

careful clinical examination (the face of Job’s syndrome!) and

determination of serum IgE are essential in diagnosing Job’s

syndrome and introducing an effective chemoprevention in

children.

22

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