STUDY Dermatitis and the Newborn Rash of Hyper-IgE Syndrome Cheryl Lee D. Eberting, MD; Joie Davis, APRN, APNG; Jennifer M. Puck, MD; Steven M. Holland, MD; Maria L. Turner, MD Objective: To characterize the dermatitis, the new- person or telephone interview of the parent or caregiver born rash, and cutaneous findings in hyper-IgE syn- of each patient. drome, also known as Job’s syndrome. Results: Twenty-eight (65%) of 43 patients fulfilled the Design: Prospective and retrospective evaluation and criteria for atopic dermatitis. Thirty-five (81%) of 43 pa- treatment of cutaneous manifestations in patients with a tients reported a newborn rash. Eight (19%) of 43 were clinical diagnosis of hyper-IgE syndrome (HIES). born with the rash; 23 (53%) of 43 had acquired the rash Analysis of the newborn rash encountered in this popu- within 7 days; 32 (74%) of 43 within 14 days; 34 (79%) lation. of 43 within 30 days; and 35 (81%) of 43 had the rash within 35 days of birth. Setting: Dermatology clinic at the National Institutes of Health, Bethesda, Md. Conclusions: The dermatitis in HIES resembles classic atopic dermatitis but may have distinctive features. A new- Patients: Forty-three patients seen in our clinic be- born rash is almost always a presenting sign of HIES. Af- tween January 1998 and August 2003 who had a clini- ter the newborn period, skin findings include retroau- cal diagnosis of HIES. ricular fissures, external otitis, infected dermatitis of the axillae and groin, folliculitis of the upper back and shoul- Interventions: The UK Working Party’s Diagnostic Cri- ders, cutaneous abscesses, mucocutaneous candidiasis, teria for Atopic Dermatitis were used to assess for atopic and in some patients pitted scarring of the face. dermatitis in this population. To assess the newborn rash, we performed a retrospective chart review and an in- Arch Dermatol. 2004;140:1119-1125 N 1966, DAVISETAL1 COINED THE sis has identified a dominant inheritance term Job’s syndrome to describe pattern in some instances, with at least 1 the condition of 2 girls with se- disease locus for HIES on chromosome 4, vere dermatitis, recurrent staphy- although a gene has not been identified.5 lococcal infections with “cold” Patients with HIES are susceptible to abscess formation, and an abnormal in- superficial and systemic bacterial and fun- I 1 flammatory response. In 1972, Buckley et gal infections. Staphylococcus aureus fre- al2 further defined this syndrome (Buck- quently causes abscesses of the skin and ley syndrome) in 2 boys with similar prob- lungs; Candida albicans leads to mucocu- lems: severe dermatitis, recurrent cutane- taneous candidiasis; and Aspergillus spe- ous, pulmonary, and joint abscesses, cies commonly superinfect pneumato- growth retardation, coarse facies, and ex- celes and contribute to lung disease.4,6 From the Dermatology Branch, aggerated immediate hypersensitivity as- The dermatitis in HIES has been de- Center for Cancer Research, sociated with markedly elevated serum IgE scribed in many ways. Davis et al1 re- National Cancer Institute levels and eosinophilia. Today, this syn- ferred to it as “infected eczematoid skin (Drs Eberting and Turner), the drome is known as hyper-IgE syndrome lesions.”1 Buckley et al2 reported a gener- National Human Genome (HIES).3 Recent reports delineate addi- alized dermatitis that was similar to, but Research Institute (Ms Davis tional associations, including retention of atypical for, atopic dermatitis. Donabe- and Dr Puck), and the National 3 Institute of Allergy and primary teeth owing to failure of root re- dian and Gallin documented that all of Infectious Diseases sorption, scoliosis, joint hyperextensibil- their patients had “eczematoid rashes.” Er- 7 (Dr Holland), Bethesda, Md. ity, frequent bone fractures, and distinc- lewyn-Lajeunesse noted that the distri- The authors have no relevant tive facial features that were found to be bution of the rash in HIES was atypical for financial interest in this article. universal by age 16 years.4 Genetic analy- true atopic dermatitis. Because the treat- (REPRINTED) ARCH DERMATOL / VOL 140, SEP 2004 WWW.ARCHDERMATOL.COM 1119 ©2004 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/25/2021 palate, congenital anomaly, and lymphoma. An age correction 90 Body Only is applied to subjects younger than 5 years. Five of 43 patients 80 Face and/or had a HIES score between 26 and 39, and the remainder scored Scalp Only 40 or higher. The average HIES score for all 43 patients was 61.2. 70 Face and/or Scalp and Body 60 PROCEDURE 50 The UK Working Party’s Diagnostic Criteria for Atopic Der- 40 matitis were applied to all 43 patients. Compliance with these criteria was determined by a brief examination and evalua- 30 Patients Affected, % tions of patient responses to a survey. To meet the criteria, pa- 20 tients must have had an itchy skin condition in the past year plus 3 or more of the following symptoms: (1) history of in- 10 volvement of the skin creases such as folds of elbows (antecu- 0 bital), behind the knees (popliteal), fronts of ankles, or around 0 7 14 21 28 35 Age, d the neck (including cheeks in children younger than 10 years); (2) a personal history of asthma or hay fever (or history of atopic disease in a first-degree relative in children younger than 4 years); Figure 1. Study patients affected with newborn rash of hyper-IgE syndrome by age 35 days. (3) generally dry skin in the past year; (4) flexural dermatitis at the time of examination; and (5) onset before age 2 years (criteria not used in children younger than 4 years).9-11 A retrospective chart review was done to obtain any his- ment and prognosis of HIES is quite different from that tory regarding a newborn rash. A patient was considered to have of atopic dermatitis, it is important to differentiate the had a newborn rash if the onset was within the first 35 days of 8 two. In an effort to assess whether patients with HIES life, was persistent, and was papulopustular in nature. Pa- have atopic dermatitis, we applied the UK Working Par- tients, and in most cases patients’ mothers, were questioned re- ty’s Diagnostic Criteria for Atopic Dermatitis9-11 to our garding whether the patient “had a rash at birth or shortly there- cohort of patients. after.” If the respondent answered in the negative, no further There have also been many reports of newborn rashes questions were asked. If the respondent answered in the affir- in HIES.12-16 Most recently, Chamlin et al12 described the mative, the distribution, appearance, and course of this rash newborn rash as a papulopustular eruption predomi- were also elicited. Effort was made to ask open-ended, non- nantly affecting the face and scalp in the first year of life, leading questions. with the eruption beginning within the first month of life in 6 of their 8 patients. In the present study, a retrospec- RESULTS tive review of the medical records and interviews with the parents or caregivers of each patient allowed us to deter- Of the 43 patients, 28 (65%) fulfilled the UK Working Par- mine the frequency, timing, and characteristics of the new- ty’s Diagnostic Criteria for Atopic Dermatitis. Thirty-five born rash of HIES. We also noted several other common (81%) of 43 patients reported having an itchy skin con- skin manifestations of HIES and devised effective thera- dition in the past 12 months. Thirty-two (74%) of 43 re- peutic strategies for the management of the recalcitrant cu- ported that this itchy condition began before age 2 years. taneous manifestations in this patient population. Thirty-one (72%) of 43 gave a history of flexural involve- ment of dermatitis at some point in their life, but only 12 (28%) of 43 had flexural involvement at the time of evalu- METHODS ation. Twenty-two (51%) of 43 gave a history of asthma PATIENTS and 14 (33%) of 43 gave a history of hay fever. Twenty- eight (67%) of 42 reported dry skin in the past year. Between January 1998 and August 2003, the dermatology ser- Thirty-five (81%) of the 43 patients in the study gave vice at the National Institutes of Health in Bethesda, Md, evalu- a history of having the typical newborn rash of HIES within ated 43 patients from various ethnic backgrounds who had a the first 35 days of life (Figure 1): 8 (19%) of 43 were clinical diagnosis of HIES, 27 female and 16 male (aged 3-50 born with the rash; 23 (53%) of 43 developed the rash years; mean age, 23 years). Patients were studied under ap- proved protocols at the Warren Grant Magnuson Clinical Cen- within the first 7 days of life; 32 (74%) of 43 within the ter, National Institutes of Health, Bethesda. Informed consent first 14 days of life; and 34 (79%) of 43 within the first 30 was obtained from all subjects or their parents. Of the 43 pa- days of life. The average age of onset was 7 days. tients included in this study, 18 were described in 1999.4 In 33 of the 35 patients with the newborn rash, the The diagnosis of HIES must be made clinically because there face (Figure 2A) or scalp was the first area to be in- are no genetic or other confirmatory tests available. Inclusion volved. Of these 33 patients, 26 reported that the rash pro- in this study was based on an assessment by clinicians familiar gressed to include other parts of the body. The rash started with the syndrome and assisted by the scoring method for fa- 5 on the neck in 1 patient and on the buttocks in another.