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Job Syndrome Medication

  • Author: Jennifer Heimall, MD; Chief Editor: Michael A Kaliner, MD  more...
 
Updated: Apr 05, 2016
 

Medication Summary

The goals of pharmacotherapy are to reduce morbidity and prevent complications.

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Antibiotics

Class Summary

Empiric therapy should be comprehensive in the context of the clinical setting.

Sulfamethoxazole (SMZ) and trimethoprim (TMP) (Bactrim, Bactrim DS)

 

Inhibits bacterial growth by inhibiting synthesis of dihydrofolic acid.

Antibacterial activity of TMP-SMZ includes common urinary tract pathogens, except Pseudomonas aeruginosa.

Azithromycin (Zithromax, Z-Pak)

 

Acts by binding to 50S ribosomal subunit of susceptible microorganisms and blocks dissociation of peptidyl tRNA from ribosomes, causing RNA-dependent protein synthesis to arrest. Nucleic acid synthesis is not affected.

Concentrates in phagocytes and fibroblasts as demonstrated by in vitro incubation techniques. In vivo studies suggest that concentration in phagocytes may contribute to drug distribution to inflamed tissues.

Treats mild-to-moderate microbial infections.

Amoxicillin and clavulanate (Augmentin)

 

Amoxicillin inhibits bacterial cell wall synthesis by binding to penicillin-binding proteins. Addition of clavulanate inhibits beta-lactamase producing bacteria.

Good alternative antibiotic for patients allergic or intolerant to the macrolide class. Usually is well tolerated and provides good coverage to most infectious agents. Not effective against Mycoplasma and Legionella species. The half-life of oral dosage form is 1-1.3 h. Has good tissue penetration but does not enter cerebrospinal fluid.

For children >3 months, base dosing protocol on amoxicillin content. Due to different amoxicillin/clavulanic acid ratios in 250-mg tab (250/125) vs 250 mg chewable-tab (250/62.5), do not use 250-mg tab until child weighs >40 kg.

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Beta2-adrenergic agonists

Class Summary

These agents are used to treat bronchospasm refractory to epinephrine.

Albuterol (ProAir HFA, Proventil, Ventolin HFA, AccuNeb)

 

Beta-agonist for bronchospasm refractory to epinephrine. Stimulates adenyl cyclase to convert ATP to cAMP and causes bronchodilation. Relaxes bronchial smooth muscle by action on beta2-receptors with little effect on cardiac muscle contractility. May decrease mediator release from mast cells and basophils and inhibit airway microvascular leakage.

Frequency may be increased. Institute regular schedule in patients on anticholinergic drugs who remain symptomatic. Available as liquid for nebulizer, MDI, and dry powder inhalers.

Continuous therapy may reduce need for mechanical ventilation.

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Nutritional Supplement

Class Summary

Calcium supplements are used to strengthen bones.

Calcium carbonate (Oyster Shell Calcium, Cal-Carb Forte)

 

Calcium supplementation in patients at young ages has been proven to lower the incidence of fractures.

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Vitamin, Fat Soluble

Class Summary

Agents that promote calcium absorption are used.

Cholecalciferol (Vitamin D3)

 

Promotes absorption of calcium and phosphorus in small intestine. Promotes renal tubule resorption of phosphate. Increases rate of accretion and resorption in bone minerals.

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Antifungal agents

Class Summary

These agents are used to treat mucocutaneous candidiasis and onychomycosis.

Itraconazole (Sporanox)

 

Fungistatic activity. Synthetic triazole antifungal agent that slows fungal cell growth by inhibiting CYP-450–dependent synthesis of ergosterol, a vital component of fungal cell membranes.

Fluconazole (Diflucan)

 

Synthetic oral antifungal (broad-spectrum bistriazole) that selectively inhibits fungal cytochrome P-450 and sterol C-14 alpha-demethylation, which prevents conversion of lanosterol to ergosterol, thereby disrupting cellular membranes. Has little affinity for mammalian cytochromes, which is believed to explain its low toxicity. Available as tablets for oral administration, as a powder for oral suspension, and as a sterile solution for IV use. Has fewer adverse effects and better tissue distribution than older systemic imidazoles.

Daily dose varies with indication.

Posaconazole (Noxafil)

 

Triazole antifungal agent. Blocks ergosterol synthesis by inhibiting the enzyme lanosterol 14-alpha-demethylase and sterol precursor accumulation. This action results in cell membrane disruption. Available as oral susp (200 mg/5 mL). Indicated for prophylaxis of invasive Aspergillus and Candida infections in patients at high risk because of severe immunosuppression.

Voriconazole (Vfend)

 

Used for primary treatment of invasive aspergillosis and salvage treatment of Fusarium species or Scedosporium apiospermum infections. A triazole antifungal agent that inhibits fungal CYP450-mediated 14 alpha-lanosterol demethylation, which is essential in fungal ergosterol biosynthesis.

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Contributor Information and Disclosures
Author

Jennifer Heimall, MD Clinical Fellow, Department of Allergy and Immunology, National Institutes of Health-NIAID

Jennifer Heimall, MD is a member of the following medical societies: American Academy of Allergy Asthma and Immunology, American Academy of Pediatrics, American College of Allergy, Asthma and Immunology, American College of Physicians-American Society of Internal Medicine, American Medical Association

Disclosure: Nothing to disclose.

Coauthor(s)

Alexandra Freeman, MD Staff Clinician, Laboratory of Clinical Infectious Diseases, NIAID, NIH

Alexandra Freeman, MD is a member of the following medical societies: American Academy of Pediatrics, Infectious Diseases Society of America, Pediatric Infectious Diseases Society

Disclosure: Nothing to disclose.

Steven M Holland, MD Assistant Professor of Medicine, Department of Medicine, Johns Hopkins Hospital; Chief, Laboratory of Clinical Infectious Diseases, Chief, Infectious Diseases Program, National Institute of Allergy and Infectious Diseases, National Institutes of Health

Steven M Holland, MD is a member of the following medical societies: American Association for the Advancement of Science, American College of Physicians, American Medical Association, American Society for Microbiology, Infectious Diseases Society of America

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Chief Editor

Michael A Kaliner, MD Clinical Professor of Medicine, George Washington University School of Medicine; Medical Director, Institute for Asthma and Allergy

Michael A Kaliner, MD is a member of the following medical societies: American Academy of Allergy Asthma and Immunology, American Association of Immunologists, American College of Allergy, Asthma and Immunology, American Society for Clinical Investigation, American Thoracic Society, Association of American Physicians

Disclosure: Nothing to disclose.

Additional Contributors

Charles H Kirkpatrick, MD 

Charles H Kirkpatrick, MD is a member of the following medical societies: American Academy of Allergy Asthma and Immunology, American Association of Immunologists, American College of Physicians, American Society for Clinical Investigation, Clinical Immunology Society, American Federation for Clinical Research

Disclosure: Received consulting fee from Dyax for consulting.

Acknowledgements

The authors would like to acknowledge the patients with HIES and their families who have generously aided in our understanding of this fascinating syndrome.

References
  1. Davis SD, Schaller J, Wedgwood RJ. Job's Syndrome. Recurrent, "cold", staphylococcal abscesses. Lancet. 1966 May 7. 1(7445):1013-5. [Medline].

  2. Buckley RH, Wray BB, Belmaker EZ. Extreme hyperimmunoglobulinemia E and undue susceptibility to infection. Pediatrics. 1972 Jan. 49(1):59-70. [Medline].

  3. Grimbacher B, Holland SM, Puck JM. Hyper-IgE syndromes. Immunol Rev. 2005 Feb. 203:244-50. [Medline].

  4. Minegishi Y, Saito M, Tsuchiya S, Tsuge I, Takada H, Hara T. Dominant-negative mutations in the DNA-binding domain of STAT3 cause hyper-IgE syndrome. Nature. 2007 Aug 30. 448(7157):1058-62. [Medline].

  5. Holland SM, DeLeo FR, Elloumi HZ, Hsu AP, Uzel G, Brodsky N. STAT3 mutations in the hyper-IgE syndrome. N Engl J Med. 2007 Oct 18. 357(16):1608-19. [Medline].

  6. Sowerwine KJ, Holland SM, Freeman AF. Hyper-IgE syndrome update. Ann N Y Acad Sci. 2012 Feb. 1250:25-32. [Medline].

  7. Chandesris MO, Melki I, Natividad A, Puel A, Fieschi C, Yun L, et al. Autosomal dominant STAT3 deficiency and hyper-IgE syndrome: molecular, cellular, and clinical features from a French national survey. Medicine (Baltimore). 2012 Jul. 91(4):e1-19. [Medline].

  8. Minegishi Y, Saito M. Molecular mechanisms of the immunological abnormalities in hyper-IgE syndrome. Ann N Y Acad Sci. 2011 Dec. 1246:34-40. [Medline].

  9. Milner JD, Brenchley JM, Laurence A, Freeman AF, Hill BJ, Elias KM, et al. Impaired T(H)17 cell differentiation in subjects with autosomal dominant hyper-IgE syndrome. Nature. 2008 Apr 10. 452(7188):773-6. [Medline]. [Full Text].

  10. Freeman AF, Kleiner DE, Nadiminti H, Davis J, Quezado M, Anderson V. Causes of death in hyper-IgE syndrome. J Allergy Clin Immunol. 2007 May. 119(5):1234-40. [Medline].

  11. Leonard GD, Posadas E, Herrmann PC, Anderson VL, Jaffe ES, Holland SM. Non-Hodgkin's lymphoma in Job's syndrome: a case report and literature review. Leuk Lymphoma. 2004 Dec. 45(12):2521-5. [Medline].

  12. O'Connell AC, Puck JM, Grimbacher B, Facchetti F, Majorana A, Gallin JI, et al. Delayed eruption of permanent teeth in hyperimmunoglobulinemia E recurrent infection syndrome. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2000 Feb. 89(2):177-85. [Medline].

  13. Ling JC, Freeman AF, Gharib AM, Arai AE, Lederman RJ, Rosing DR. Coronary artery aneurysms in patients with hyper IgE recurrent infection syndrome. Clin Immunol. 2007 Mar. 122(3):255-8. [Medline].

  14. Freeman AF, Collura-Burke CJ, Patronas NJ, et al. Brain abnormalities in patients with hyperimmunoglobulin E syndrome. Pediatrics. 2007 May. 119(5):e1121-5. [Medline].

  15. Ozcan E, Notarangelo LD, Geha RS. Primary immune deficiencies with aberrant IgE production. J Allergy Clin Immunol. 2008 Dec. 122(6):1054-62; quiz 1063-4. [Medline].

  16. Jonczyk-Potoczna K, Szczawinska-Poplonyk A, Warzywoda M, Breborowicz A, Pawlak B. Hyper Ig E syndrome (Job syndrome, HIES) - radiological images of pulmonary complications on the basis of three cases. Pol J Radiol. 2012 Apr. 77(2):69-72. [Medline]. [Full Text].

 
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STAT3 gene is diagrammed with depiction of hotspots (areas where higher numbers of patients were noted to have mutations).
HIES scoring sheet. A score >40 is considered likely HIES, 20-40 indeterminate, < 20 unlikely HIES.
Recurrent pneumonias, particularly those due to S aureus, may lead to pneumatocele formation. Pneumatoceles such as those demonstrated in this CT image may then allow fungal superinfection.
Brain hyperintensities have been noted to be present with increased frequency in patients of all ages with Job syndrome.
Table. Scoring System for Job Syndrome
  0 1 2 3 4 5 6 7 8 10
Clinical Findings                    
Highest IgE (IU/mL) < 200 200-500     501-1000       1001-2000 >2000
Total # skin abscesses/boils None   1-2   3-4       >4  
Total # pneumonias None   1   2   3   >3  
Parenchymal lung abnormalities None           Bronchiectasis   Pneumatocele  
Other serious infection None       Present          
Fatal infection None       Present          
Highest eosinophils/uL < 700     701-800     >800      
Newborn rash None       Present          
Eczema (worst stage) None Mild Moderate   Severe          
Sinusitis/otitis (# in worst year) 1-2 3 4-6   >6          
Candidiasis None Oral, vaginal Fingernail   Systemic          
Retained primary teeth None 1 2   3       >3  
Scoliosis (max. curvature) < 10   10-14   15-20       >20  
Minimal trauma fractures None       1-2       >2  
Hyperextensibility None       Present          
Characteristic face None   Mild     Present        
Increased interalar distance < 1 SD 1-2 SD   >2 SD            
High palate None   Present              
Congenital anomaly None         Present        
Lymphoma None       Present          
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