|Year : 2013 | Volume
| Issue : 3 | Page : 95-97
Tuberculous osteomyelitis in Job syndrome
Goadara Shilpa, Vikram Singhal, Rajesh Mahabala Shimoga, Kiram Baliga
Department of Pediatrics, Kasturba Medical College, Manipal University, Mangalore, Karnataka, India
|Date of Web Publication||26-Nov-2013|
H. No. 8, Ram Nagar, Gobindpuri, Yamuna Nagar - 135 001, Haryana
Source of Support: None, Conflict of Interest: None
Job syndrome (JS) is a rare primary immunodeficiency disorder characterized by the triad of raised serum immunoglobulin E levels, recurrent skin and pulmonary infections. A 6-year-old boy presented with the characteristic triad of JS and left leg swelling, which on evaluation was found to be tuberculous osteomyelitis. JS being an immunocompromised state can predispose to tuberculous infections and one has to be vigilant enough for early diagnosis and treatment to prevent deformity.
Keywords: Immunoglobulin E, infections, osteomyelitis
|How to cite this article:|
Shilpa G, Singhal V, Shimoga RM, Baliga K. Tuberculous osteomyelitis in Job syndrome. Indian J Paediatr Dermatol 2013;14:95-7
|How to cite this URL:|
Shilpa G, Singhal V, Shimoga RM, Baliga K. Tuberculous osteomyelitis in Job syndrome. Indian J Paediatr Dermatol [serial online] 2013 [cited 2019 Nov 15];14:95-7. Available from: http://www.ijpd.in/text.asp?2013/14/3/95/122179
| Introduction|| |
Job syndrome (JS) is a primary immunodeficiency disease characterized by elevated plasma immunoglobulin E (IgE) (>1000 IU/ml) and recurring respiratory and cutaneous infections with craniofacial and bone growth changes.  The disease is named after the biblical character Job whose body was covered with pustules. A 6-year-old boy presented with recurrent pustular skin lesions and on evaluation was found to have classical features of JS with tuberculous osteomyelitis of left tibia and fibula.
| Case Report|| |
A 6-year-old boy with grade I malnutrition presented with low-grade intermittent fever associated with painful limp on the left side and swelling at lower lateral border of left leg since 15 days. Child also had pustules with occasional oozing distributed all over the body, but denser in bilateral groins and scalp, for which child had been taking ayurvedic medications. There was history of recurrent ear discharge and frequent respiratory tract infections requiring hospitalization and two episodes of long bone fracture. There was no significant family history, other siblings being normal. Child was developmentally normal for age. There was history of allergy to egg.
Child had pallor, coarse facies, scoliosis and eczematous plaques all over the body [Figure 1] and a tender red swelling around 5 cm × 5 cm over the lateral aspect of left ankle. Systemic examination was within the normal limits
Investigations showed total white blood cells count of 24,060, erthrocyte sedimentation rate 69 and IgE levels of 27,111. X-ray left ankle showed lytic lesion in the lateral part of the distal tibia and fibula with periosteal reaction and adjacent soft-tissue swelling with abnormal growth plate and sclerotic margins of the epiphysis and metaphysic [Figure 2]. Ultasonograph left ankle showed cortical breech in lateral malleolus with the large collection 3.5 cm × 1.5 cm × 2.7 cm with multiple focal hyperechoic foci within the collection suggestive of Brodie's abscess. Mantoux showed induration of 7 mm.
A diagnosis of primary immunodeficiency was made and intravenous (i.v.) ceftriaxone and amikacin were started. Abscess was drained under general anesthesia and straw coloured exudate was sent for tuberculosis polymerase chain reaction (PCR), which was came positive and microscopically showed lymphocytes predominantly, staining for acid fast bacilli was negative. Child was started on antituberculous treatment as per directly observed treatment regime with regular change of dressings. Emollients were used for skin lesions.
|Figure 2: Lytic lesion in lateral part of distal tibia and fibula with periosteal reaction|
Click here to view
| Discussion|| |
Hyperimmunoglobulinemia E syndromes (HIE) are rare primary immunodeficiencies. JS is one of the presentations of the hyper IgE syndrome, characterized by persistent Cutaneous abscesses (caused by Staphylococcus aureus and Staphylococcus Epidermidis most commonly) and a history of recurring pneumonias, pneumatoceles, hypereosinophilia, elevated serum levels of IgE (>2,000 IU/ml) and craniofacial and bone growth changes. 
It is caused by a mutation in the signal transducer and activating factor of transcription 3 (StAt3) gene on chromosome 17q21. Most cases are sporadic, but autosomal dominant and recessive patterns with variable expressivity also exist. 
Type 1 HIE syndrome displays abnormalities in multiple systems, including the skeletal, dental and immune systems, whereas type 2 HIE syndrome shows abnormalities confined to the immune system.  Cytokine responses in both types of HIE syndrome revealed severe defects leading to impaired T-helper type 17 function, with the extent of the defective T helper type 17 response determines the clinical phenotype. 
Dermatologic features include pruritic, eczematous skin eruptions involving predominately the flexural areas and around the hairline. Staphylococcal painless abscesses so often referred to as cold abscesses may be present. Chronic mucocutaneous candidiasis and onychomycosis also may be the presenting feature.  Our patient presented with chronic eczematous skin lesions with recurrent pustule.
Respiratory manifestations may be recurrent bronchitis and a history of S. aureus or Haemophilus influenzae pneumonia, usually associated with pneumatocele, which may get superinfected with Pseudomonas eruginosa and Aspergillus fumigatus. Our patient presented with recurrent episodes of the respiratory tract infections requiring frequent admissions. Patients also may have a history of otitis externa, chronic otitis media as in this case. 
Skeletal manifestations includes recurrent bacterial arthritis and most commonly staphylococcal osteomyelitis at fracture sites.  However in this case, osteomyelitis was tuberculous in origin. Culture results in suspected osteomyelitis are often negative, but the findings on diagnostic images are usually consistent with this diagnosis.
Other features may be peripheral T-cell lymphoma,  coronary artery aneurysms, coarse facies with greater interalar width, a longer outer canthal distance, prominent brow and supraorbital ridge with the impression of deep-set eyes.  These features become more pronounced with age.
Lab studies reveals serum IgE levels greater than 2,000 IU/ml.  Serum eosinophil counts more than two standard deviations above the normal range. Elevated eosinophil counts in secretion samples, such as pus and sputum. Histologic examination of vesicopapules may reveal an eosinophil-rich infiltration. Pulmonary imaging, neutrophil chemotaxis assessment and PCR-based high-resolution deoxyribonuclic acid melting assay scanning selected exons of the STAT3 gene help in the diagnosis. 
There is no definitive therapy available. Mainstay of treatment is control of bacterial infections. Early incision and drainage followed by the i.v. antibiotics are used for cutaneous infections. Coverage is usually aimed at Staphylococcus and Haemophilus species. Response being slow requires longer duration of treatment. Chronic onychomycosis responds well to oral ketoconazole and fluconazole. Eczematous dermatitis needs high-dose topical steroids and emollients. The autosomal recessive variant may benefit from a hematopoietic stem cell graft. 
| Conclusion|| |
Early detection with proper care can prevent progression of JS. Initiate treatment at the first signs of infection to prevent long-term complications. Mild local pain should be considered a sign of possible infection and JS patients should be taught that the typical inflammatory response does not necessarily occur. Although the most common organism causing infection is Staphylococcus, the case report shows that JS also pre-disposes to tuberculous infections and a high degree of suspicion is needed for early diagnosis and treatment.
| References|| |
|1.||Grimbacher B, Holland SM, Puck JM. Hyper-IgE syndromes. Immunol Rev 2005;203:244-50. |
|2.||Minegishi Y, Karasuyama H. Genetic origins of hyper-IgE syndrome. Curr Allergy Asthma Rep 2008;8:386-91. |
|3.||van de Veerdonk FL, Marijnissen RJ, Joosten LA, Kullberg BJ, Drenth JP, Netea MG, et al. Milder clinical hyperimmunoglobulin E syndrome phenotype is associated with partial interleukin-17 deficiency. Clin Exp Immunol 2010;159:57-64. |
|4.||Hanifin JM, Cooper KD, Ho VC, Kang S, Krafchik BR, Margolis DJ, et al. Guidelines of care for atopic dermatitis, developed in accordance with the American Academy of Dermatology (AAD)/American Academy of Dermatology Association Administrative Regulations for Evidence-Based Clinical Practice Guidelines. J Am Acad Dermatol 2004;50:391-404. |
|5.||Davis SD, Schaller J, Wedgwood RJ. Job's Syndrome. Recurrent, cold, staphylococcal abscesses. Lancet 1966;1:1013-5. |
|6.||Onal IK, Kurt M, Altundag K, Aksoy S, Dincer M, Gullu I. Peripheral T-cell lymphoma and Job's syndrome: A rare association. Med Oncol 2006;23:141-4. |
|7.||Borges WG, Hensley T, Carey JC, Petrak BA, Hill HR. The face of Job. J Pediatr 1998;133:303-5. |
|8.||Renner ED, Rylaarsdam S, Anover-Sombke S, Rack AL, Reichenbach J, Carey JC, et al. Novel signal transducer and activator of transcription 3 (STAT3) mutations, reduced T (H) 17 cell numbers, and variably defective STAT3 phosphorylation in hyper-IgE syndrome. J Allergy Clin Immunol 2008;122:181-7. |
|9.||Bittner TC, Pannicke U, Renner ED, Notheis G, Hoffmann F, Belohradsky BH, et al. Successful long-term correction of autosomal recessive hyper-IgE syndrome due to DOCK8 deficiency by hematopoietic stem cell transplantation. Klin Padiatr 2010;222:351-5. |
[Figure 1], [Figure 2]