Management of recurrent lung infections in a case of hyperimmunoglobulinemia E ( or Job ' s ) syndrome

The diagnosis of hyperimmunoglobulinemia E (hyper IgE) or Job’s syndrome was made in a five-month-old girl with chronic staphylococcal mastitis, elevated serum IgE and abnormal neutrophil chemotaxis. After multiple hospitalizations for severe skin in functions, right upper lobe bullae were found and treated by lobectomy when the patient was three years of age. Thereafter, the patient was repeatedly hospitalized for pneumonia while on cloxacillin prophylaxis and receiving regular chest physiotherapy. When she was 12 years old, pulmonary deterioration (increased frequency of pulmonary infections, hemoptysis, radiological destruction or the right middle lobe) led 10 a right middle lobectomy. Since this intervention, the patient has had an improved quality nf life, takes part in regular sports activities, without recurrence of severe pulmonary infections, and has had near normal pulmonary function studies. A concerted medicosurgical therapeutic regimen can control severe pulmonary complications in patients with this rare syndrome.


CASE REPORT
T he five-month-old patie nt was diagnosed wit h hyper IgE syndrome when she presented to the pediatric clinic with a history of chronic right breast discharge s ince birth. chronic seborrheic J ermatitis. perforated otitis media and le ft cervical aden itis. Family history was pos itive for a maternal uncle with repeated cutaneous abscesses, pneumonia and multiple bouts of otitis media as a child. two maternal aunts with ch ildhood cutaneous abscesses. and several other maternal relati ves w it h chronic severe pustular lesions of the face and scalp. Physical e xamination revealed an active well looking afebrilc child wi th infected facial eczema. normal c hest, cardiovasc ul ar and abdominal examination. le ft posterior cervical adenitis and a right breast abscess. Laboratory work up revea led an increaseJ scrum IgE level ( 113 U/mL. which later increased to 15,000 U/m L) and decreased chemotaxis (assessed by the Boyden chamber technique 151). Leuko-LJ .
cyte count was 21.000x IO /L with 8'7r polymorphonuclear cells, 88'7' lymphocytes, l 7a monocytes and 2% eosinophils. Cu lt ure o r scalp. breast J ischarge and the cervical abscess were positi ve fo r Stap/irf oco< ·cus rwreus. Review of he r chart showed a positive S auffus culture of the umbilicus at two days of age. By the age of three years. the patient had had th ree hospitalizations, the first for right leg and perianal abscesses. the second for conjunctivitis and an infraorbital abscess. a nd the thi rd for severe puru lent conjunctivitis. All were cultureposit ive fo r S 011re11s. The episodes o,·curred while the patient was on oral clox::icillin prophylaxis and she responded well to a ntistaphylococcal intrave nous anti biotics. A lso, at 14 months o ld, she was fou nd to have congenital d islocati(lll uf the hip and later an associated genu valgum. which required three hospitalizations for surg i al correct ion. At the age o f th ree years the patient began to develop pulmonary complications. W hile she was hospitaliLcd for a severe ca mpylobacter gastroente ritis. routine rocntge nograms showed large bullac occupying the enti re right lung fi eld. The patient was asymptomat ic and had normal blood gases. Perfusion lung scan showed almost complete loss of perfusion to the ent ire ri ght lung but normal left lung perfus ion. After four weeks of cloxacil lin the pat ient had slight dyspnea on effort. a nd repeat chest roentgenograms showed bul lae originating in the right uppe r lobe and compressing the right m iddle and lower lobes (Fi 0 urc I). Two months later the patie nt underwent ;1 right superinr lobectomy, which was Fi1,:urc 2) /'11., 1,.,-u,1111,·1111r  wl'll to kratl'd with a11 u11L ' n ·ntf'u l postoperative cou rse . At the time or "urgery the 111id<l le and lower lobes were noted to be normal. Pa tho logy examination showed multiple bull ae wi th in chron icall y inll amed pu lmonary ti ssue.
Over the ,u hsequen t eight years, the patient was hospitali, ed thrl'e to fou r times per year fo r pneumoccoccal 1)r Can Respir J Vol 2 No 1 Spring 1995 Pulmonary complication s in hyper lgE syndrome Figure 3) Posterow !lerior chcst radiugraph (top ) 011d cu111p11ted to111ograp/1y section thro11gh th,· rnrina (bottom) ohw ined ur thl' age of 14 yeurs sh o11 · a 110r1110/ 11ostlubecto1m· chest appea1w1n· Hue111nphiius i11/l11e11;.ae pneumon ia. loca li zed to the superi or portion of the right lung, whi le on oral cloxaei llin prophy laxis . The pati ent began to experience symptoms of chronic cough and di minished exerci se tol erance, and at 12 years or age she had occasional ep isoJes or mild hernoptysis.
While the patient was hospita li zed for another hout of pneumonia, chest roentge nogram and compu terized 101110graphic (CT) scan de monst rated multiple air-fill ed cavi ties surrounded hy pulmonary opacit ies occupy ing the upper third of the right lung fi eld (Figure 2). Bronchoscopy showed unremarkable scar tissue al the site of surgery, SO'?i stenosis of the right middle lobe bronchus, and abundant white secretions in the right and left main bronchi . Bronchial lavage rnlt ure was positi ve for S a11rcus and H i1ifluc11:::ae. Bronchography rcveall"d nu merous cavities unpenctrated by contrast medium, distortion of ri g ht midd le bronchus a nd no nidencc of bronchopleural fi stula. Pulmonary function studic., suggested a mild obstructive pattern w ith a forced expiratory vol ume in I s (FEY 1) of 7 1 % and a forced vital capacity (FVC) of 90% of predicted values. T he patient responded well to intravenous antibiotic therapy, but over the next year had further freq uent hospit~1 lizati ons for rig ht upper lobe pne umonia; a repeat CT scan showed persistence of the cavities as well as atelectasis of the rig ht middle lobe with occasional areas of bronchiectasis. A second perfusion lung scan showed diminished pe rfus ion of the upper right lung. Based on the laboratory evidence of damaged middle lobe parcnchyma and the patient' s c linical deterioration over oneand-a-half years, the patie nt un<lcrwcnt a ri g ht middle lobcctomy at the age o f 13. from which she made a rapid recove ry with an unevent ful postoperative course.
In the foll owing two years. the patient has had :in improved quality of life, with normal daily activities including sports. and near normal pulmonary function studies showing normal lung volumes (greater tha n lJOCfo of predic ted values) anJ a rterial blood gases, a m ild obstructi ve spiromctry pattern (FEY 1 66<ii and FYC 83% or prc<licted val ues with a rise to FEY 1 76% and FYC 89% after inhalation of a beta2agonist). She has also had only one three-day hospitalization for mi ld pneumon ia during this time. She is still on o ral cloxacillin prophylaxis. long term regular inhaled beta2agonisl therapy a nd has daily chest physiotherapy. whic h h:1s hel ped to prevent any fu rther complicat ions.
T he chest radiograph and CT scan obtained at the age or 14 showed a normal post lobecto my appearance (Fig ure 3 ).

DISCUSSION
Job's syndrome. first re ported by Davis cl al in 1966 ( l ).
Jerives its name fro m the biblical figure Job, who was inflicted with '' boils from the so le of his foot unto his crown'" (JOB ?.:7) by Satan. In 1972 Buckley e t al (2) made a major advance in de lineati ng the syndrome. The disease is characterized by: repeated cutaneous, gang lionic. si nus and pul monary in fec tion s usually of staphyloccoca l, st reptococcal or If i11fl11e11;:,ae origin : cczcmatoicl de rmatitis that is usua ll y supcri nfccted: facial dysmorphism and coarse faci cs; retarded growth; and, rare ly, li mb deformity (6). The syndrome shows characteristic hyper IgE. many hundred ti mes above normal, a mild chcrnotactic defect and eosinophilia (7,8 ).
Pulmonary involvement is usually important and can compromise the patie nt' s pulmonary functi on to the point of severely reducing the quality of li fe and finally leading to death. Aggressive early a ntibiotic therapy together with chest physiotherapy must be instituted in order to keep pul monary damage to a m ini mum. As seen in our patient, repeated pulmonary infections may lead lo lung destruction w ith bulla fo rmation and bronchiectasis. A full pulmo nary workup in-80 eluding bronchoscopy with bacterial cultures. CT. ventilation scan a nd pulmonary funct ion studies is indicated in these patients whe n involve ment is severe, in order lo optimize medico urgical therapy.
There are few treatment modalities that have proved to be bene ficial for patie nts with hyper lgE syndrome (7,8 ). Until the unde rlying pathogenesi s is mo re full y understood. a complete pulmonary therapeutic regime n including di.cussion of early tailored surge ry is warranted for these patients. Anecdotal expe rience drnwn fro m our paticn1 and other previous case reports (3,4) suggests that removal o f the damaged lung pare nchyma can reduce morbidity and improve pulmo nary fu nction sign ificantly when conservative measures fail to cont rol repeated respiratory infect ions. The two surgical procedures performed in our patient arc in accordance with pre vious reports in hyper lgE syndrome. Pne umatoccles have been reported to be frequent in hype r lgE syndrome patients; usual pcrsistance with secondary in fectio n is common (9). Also, c urre nt practice g uide lines in thoracic surgery advise a lobectomy for locali zed bronchiectasis in the presence of symptomatic and recurrent pneumonia refractory to medica l treatment. recurrent he mophysis and adequate predicted postope rative lung function ( I 0). Surgery combined with an aggressive medical reg imen with frequent follow-up visits reduce hospitalizations, optimi ze pulmonary function, i111prove the quality of life and a llow a child with a chronic debilitat ing illness to live norma ll y.