What Are The Clinical Characteristics of Hyper IgE Syndrome?

Patient Presentation
An 18-month-old female came to clinic with a history of ‘bumps’ on her legs for ~5 weeks. The lesions had increased in number and in size but had not caused any problems with pain, movement, or playing. Recently, one lesion on the left knee had become slightly red. She was otherwise well.

The past medical history showed atopic dermatitis, one ear infection several months ago, and intermittent upper respiratory tract infections.

The family history was negative for any rheumatological disease including Sjörgren’s syndrome, systemic lupus erythematosus and sarcoidosis. There was no cancer, or bone problems. There was glaucoma in older paternal relatives.

The review of systems was negative for any weight loss, night sweating, fevers, chills, rashes, eye changes, other masses or intercurrent illnesses.

The pertinent physical exam showed a smiley female with growth parameters in the 50-90% and appropriate weight gain since a preceding visit. She was afebrile and the rest of her vital signs were normal. Abdominal examination showed normal liver and spleen size with no masses She had some shoddy anterior cervical and inguinal adenopathy that were all less than 0.5 cm. Skin examination showed a normal angle of nail beds and no changes in the umbilicus. Her skin was generally dry without excoriation. On the left anterior knee was a 2 cm slightly red mass that was mobile, non tender and not warm. The right anterior knee lateral to the insertion of the patella had a 1.5 cm mass that had similar characteristics. The right calf in the center of the bodies of the gastrocnemius muscle and media/anterior muscle group had a 0.5 cm mass that was difficult to palpate between the muscle bodies. There was normal range of motion in all joints.

The differential diagnosis at this time was extensive so an initial evaluation was begun. The radiologic evaluation with an ultrasound found a homogenous mass without defining characteristics for a tumor nor abscess.

The laboratory evaluation included a complete blood count, erythrocyte sedimentation rate, C-reactive protein, lactate dehydrogenase, uric acid and rheumatoid factor which all were normal. Quantitative immunoglobulins were also sent after a telephone discussion with a rheumatologist. All were normal with the exception of the IgE which was 425 IU/ml (normal up to 60) that was reported 3 days later.

The diagnosis of possible hyperimmunoglobulin E syndrome was made.

The patient’s clinical course simultaneously showed her re-presenting to her pediatrician because of a sudden increase in the size, warmth and tenderness of the lesions over her knees, but without a fever. The patient was taken to the operating room for an incision and drainage of carbuncles/abscesses that were ~5 cm bilaterally. Staphylococcus aureus that was sensitive to clindamycin was cultured. She did well on oral antibiotics and was discharged home with follow-up with her pediatrician and a referral to an immunologist for further evaluation of a possible immunodeficiency.

Case Image

Figure 74 – Transverse ultrasound image of the left calf
just inferior to the patella shows a well circumscribed, hypoechoic
lesion in the sucutaneous tissues that is hypervascular in nature.
Differential diagnosis included abscess versus involuting hemangioma.

Discussion
Children with immunodeficiencies can present in many ways including failure to thrive, weight loss, poor weight gain, diarrhea, cough, recurrent infections, unusual infection organisms, or unusual infection organ locations. There is no absolute indicator as to when a child should be evaluated for a potential immune problem. For a review of possible indications for an immunological workup and what evaluation to consider, please review “What Should I Order for An Immune Workup?”

Although the numbers are debated there are more than 80 primary immunodeficiencies. Some of the common primary immunodeficiencies are listed below along with their genetics transmission if known.

  • B-cell differentiation
    • Common variable immunodeficiency - genetics are undetermined
    • Selective IgA deficiency
    • X-linked agammaglobulinemia or Bruton’s agammaglobulinemia – X-linked
  • T-cell defects and combined B-cell and T-cell defects
    • Ataxia-telangiectasia – autosomal recessive
    • DiGeorge syndrome – autosomal dominant or spontaneous
    • Severe combined immunodeficiency – X-linked
      • T-cell deficient, B-cell competent or deficient – autosomal recessive
    • Wiskott-Aldrich syndrome – X-linked
    • X-linked hyper IgM - X-linked
  • Complement deficiencies – autosomal recessive, autosomal dominant, or X-linked
  • Phagocytic disorders
    • Chronic granulomatous disease – X-linked or autosomal recessive

Learning Point
Hyperimmunoglobulin E syndrome (Hyper IgE syndrome) is a primary immunodeficiency that is idiopathic. Some genetic linkages have been demonstrated in some families. Neutrophil chemotaxis and oxidative burst reaction problems have been noted as well as qualitative T-cell and B-cell abnormalities. It is sometimes referred to as Job Syndrome from a reference in the bible to the Prophet Job’s being afflicted by God with ulcers, boils, painful sores, grievous botch and/or other descriptions of severe skin diseases depending on the reference.

The clinical syndrome has recurrent abscess formation, severe dermatitis, respiratory tract infections and very high titres of IgE.

The skin involvement is usually quite severe and commonly occurs within several weeks of birth and is eczema like. Furuncles, carbuncles and cellulitis also occur. The abscesses are “cold” abscesses and are pathognomic to hyper-IgE syndrome but are not essential to the diagnosis. Cold abscesses are large masses and are not tender, and not associated with systemic symptoms such as fever. Staphylococcus aureus is grown from cold abscesses. Cutaneous candidiasis and thrush also occur. Invasive fungal infections also can occur.

Respiratory infections again are recurrent and severe usually caused by Staphylococcus aureus. Pneumonias are frequently complicated and cause bronchiectasis, bronchopleural fistulae and pneumatocoeles.

Sino-pulmonary and bone infections are common. Common organisms are Staphylococcus but opportunistic infections also occur with Pneumocystis carinii and Norcardia.

Skeletal abnormalities include osteopenia and increased fractures. Patients also commonly have retained primary dentitia. Facial abnormalities usually are identified by age 16 years with prominent foreheads, wide base to the nose, and a wide outer-canthal distance. Craniosynostosis and midline facial defects have been reported.

Treatment is with meticulous skin care, prophylactic antibiotics, and prompt treatment for infections. Various immunotherapies can also be tried.

Questions for Further Discussion
1. What is the differential diagnosis of masses located around the knees?

Related Cases

To Learn More
To view pediatric review articles on this topic from the past year check PubMed.

Evidence-based medicine information on this topic can be found at SearchingPediatrics.com, the National Guideline Clearinghouse and the Cochrane Database of Systematic Reviews.

Information prescriptions for patients can be found at MedlinePlus for this topic: Immune System and Disorders

To view current news articles on this topic check Google News.

To view images related to this topic check Google Images.

Erlewyn-Lajeunesse MD. Hyperimmunoglobulin-E syndrome with recurrent infection: a review of current opinion and treatment. Pediatr Allergy Immunol. 2000 Aug;11(3):133-41.

Sullivan KE. Primary care and primary immunodeficiencies. Am Fam Physician. 2003 Nov 15;68(10):1919, 19.

DeWitt CA, Bishop AB, Buescher LS, Stone SP. Hyperimmunoglobulin E syndrome: two cases and a review of the literature. J Am Acad Dermatol. 2006 May;54(5):855-65.

Jyonouchi H. Hyperimmunoglobulinemia E (Job) Syndrome. eMedicine. Available from the Internet at http://emedicine.medscape.com/article/886988-overview (rev. 5/21/2007, cited 1/9/09).

ACGME Competencies Highlighted by Case

  • Patient Care
    1. When interacting with patients and their families, the health care professional communicates effectively and demonstrates caring and respectful behaviors.
    2. Essential and accurate information about the patients’ is gathered.
    3. Informed decisions about diagnostic and therapeutic interventions based on patient information and preferences, up-to-date scientific evidence, and clinical judgment is made.
    4. Patient management plans are developed and carried out.
    5. Patients and their families are counseled and educated.
    7. All medical and invasive procedures considered essential for the area of practice are competently performed.
    8. Health care services aimed at preventing health problems or maintaining health are provided.
    9. Patient-focused care is provided by working with health care professionals, including those from other disciplines.

  • Medical Knowledge
    10. An investigatory and analytic thinking approach to the clinical situation is demonstrated.
    11. Basic and clinically supportive sciences appropriate to their discipline are known and applied.

  • Practice Based Learning and Improvement
    13. Information about other populations of patients, especially the larger population from which this patient is drawn, is obtained and used.

  • Interpersonal and Communication Skills
    19. The health professional works effectively with others as a member or leader of a health care team or other professional group.

  • Systems Based Practice
    25. Quality patient care and assisting patients in dealing with system complexities is advocated.

    Author
    Donna M. D’Alessandro, MD
    Professor of Pediatrics, University of Iowa Children’s Hospital