Indian J Pediatr DOI 10.1007/s12098-014-1613-2
SCIENTIFIC LETTER
Recurrent Meningitis in Hyper IgE Syndrome Mallesh Kariyappa & Anitha Kommalur & Shantala Jayaram & Prakash Javarappa & Arunkumar Ambazhagan
Received: 15 March 2014 / Accepted: 15 October 2014 # Dr. K C Chaudhuri Foundation 2014
To the Editor: A 12-y-old boy presented with altered sensorium with convulsions of 1 d. Child had been treated for chronic suppurative otitis media (CSOM) and streptococcal meningitis in preceding 2 y. Vital signs were stable with evident meningeal irritation. Patient had coarse skin with hypo pigmented macules, broad forehead, widely placed deep eyes and high-arched palate (Fig. 1). Cerebrospinal fluid analysis revealed 486 cells/mm3 with neutrophil predominance, reduced sugar and elevated protein. Gram staining and culture were negative. Ear discharge yielded Staphylococcus aureus. Computed tomography revealed bilateral mastoiditis Fig. 1 Photograph of the child showing hypopigmented lesions on extensor surface of upper limbs (a) and facial features of hyper IgE syndrome (b)
M. Kariyappa : A. Kommalur : S. Jayaram : P. Javarappa : A. Ambazhagan Department of Pediatrics, Bangalore Medical College and Research Institute, Fort, Bangaluru, Karnataka, India M. Kariyappa (*) 207/A-3, Sharavathi Block, National Games Village, Koramangala-23, Bangaluru, Karnataka, India e-mail: [email protected]
with CSOM. IgG was 1,720 mg/dl (400–1,590 mg/dl), IgM-116 mg/dl (30–265 mg/dl), IgA-482 mg/dl (50– 462 mg/dl), IgE 6,958 IU/ml (normal < 250 IU/ml), C4–51 mg/dl (14–44 mg/dl) and C3–269 mg/dl (70– 170 mg/dl). Child recovered with appropriate antibiotics. Child was later immunized with H.influenza and pneumococcal polysaccharide vaccines. Recurrent bacterial meningitis is defined as second episode of bacterial meningitis resulting from a different bacterial pathogen than the first, or from the same organism but occurs more than 3 wk after the completion of therapy for the initial
Indian J Pediatr
episode [1]. There are only two reported cases of meningitis by Hyper IgE syndrome (HIES). HIES is characterized by triad of recurrent staphylococcal abscesses, recurrent airway infections and increased IgE levels along with absence of allergy either in child or family members [2]. Atopic like rash and coarse skin, broad nasal base, frontal bossing, hypertelorism and deep-set eyes have been described. IgE levels above 2,000 IU/ml alone is diagnostic although there is a scoring system with score of >40 consistent with HIES [3, 4]. Score of 32 in our child is consistent with one registry where only five out of 22 patients had scores more than 40 [5]. It is inherited either as an autosomal dominant disorder with STAT3 mutations or autosomal recessive with DOCK8 mutation. Mutations in the STAT3 gene are responsible for the deficient translation of the cytokine signals in effective immune responses. Mutations in DOCK8 causes impaired binding of cytokines to the receptors. Management includes treatment of infections, supportive care and immunization. Recombinant human IFN-gamma, levamisole, ascorbic acid, rituximab have limited use [3]. These children need to be followed-up for infections and malignancies.
Conflict of Interest None. Source of Funding None.
References 1. Kline MW. Review of recurrent bacterial meningitis. Pediatr Infect Dis J. 1989;8:630–4. 2. Grimbacher B, Holland SM, Puck JM. Hyper-IgE syndromes. Immunol Rev. 2005;203:244–50. 3. Erlewyn- Lajeunesse MD. Hyper immunoglobulin-E syndrome with recurrent infection: a review current opinion and treatment. Pediatr Allergy Immunol. 2004;11:133–41. 4. Hsu AP, Davis J, Puck JM, Holland SM, Freeman AF. Autosomal dominant hyper IgE syndrome. 2010 Feb 23 [Updated 2012 Jun 7]. In: Pagon RA, Adam MP, Bird TD, et al., editors. Gene Reviews™ Internet]. Seattle (WA): University of Washington, Seattle; 1993– 2014. Available from: http://www.ncbi.nlm.nih.gov/books/ NBK25507 5. Moin M, Farhoudi A, Movahedi M, Rezaei N, Pourpak Z, Yeganeh M, et al. The clinical and laboratory survey of Iranian patients with hyperIgE syndrome. Scand J Infect Dis. 2006;38:898–903.
SCIENTIFIC LETTER
Recurrent Meningitis in Hyper IgE Syndrome Mallesh Kariyappa & Anitha Kommalur & Shantala Jayaram & Prakash Javarappa & Arunkumar Ambazhagan
Received: 15 March 2014 / Accepted: 15 October 2014 # Dr. K C Chaudhuri Foundation 2014
To the Editor: A 12-y-old boy presented with altered sensorium with convulsions of 1 d. Child had been treated for chronic suppurative otitis media (CSOM) and streptococcal meningitis in preceding 2 y. Vital signs were stable with evident meningeal irritation. Patient had coarse skin with hypo pigmented macules, broad forehead, widely placed deep eyes and high-arched palate (Fig. 1). Cerebrospinal fluid analysis revealed 486 cells/mm3 with neutrophil predominance, reduced sugar and elevated protein. Gram staining and culture were negative. Ear discharge yielded Staphylococcus aureus. Computed tomography revealed bilateral mastoiditis Fig. 1 Photograph of the child showing hypopigmented lesions on extensor surface of upper limbs (a) and facial features of hyper IgE syndrome (b)
M. Kariyappa : A. Kommalur : S. Jayaram : P. Javarappa : A. Ambazhagan Department of Pediatrics, Bangalore Medical College and Research Institute, Fort, Bangaluru, Karnataka, India M. Kariyappa (*) 207/A-3, Sharavathi Block, National Games Village, Koramangala-23, Bangaluru, Karnataka, India e-mail: [email protected]
with CSOM. IgG was 1,720 mg/dl (400–1,590 mg/dl), IgM-116 mg/dl (30–265 mg/dl), IgA-482 mg/dl (50– 462 mg/dl), IgE 6,958 IU/ml (normal < 250 IU/ml), C4–51 mg/dl (14–44 mg/dl) and C3–269 mg/dl (70– 170 mg/dl). Child recovered with appropriate antibiotics. Child was later immunized with H.influenza and pneumococcal polysaccharide vaccines. Recurrent bacterial meningitis is defined as second episode of bacterial meningitis resulting from a different bacterial pathogen than the first, or from the same organism but occurs more than 3 wk after the completion of therapy for the initial
Indian J Pediatr
episode [1]. There are only two reported cases of meningitis by Hyper IgE syndrome (HIES). HIES is characterized by triad of recurrent staphylococcal abscesses, recurrent airway infections and increased IgE levels along with absence of allergy either in child or family members [2]. Atopic like rash and coarse skin, broad nasal base, frontal bossing, hypertelorism and deep-set eyes have been described. IgE levels above 2,000 IU/ml alone is diagnostic although there is a scoring system with score of >40 consistent with HIES [3, 4]. Score of 32 in our child is consistent with one registry where only five out of 22 patients had scores more than 40 [5]. It is inherited either as an autosomal dominant disorder with STAT3 mutations or autosomal recessive with DOCK8 mutation. Mutations in the STAT3 gene are responsible for the deficient translation of the cytokine signals in effective immune responses. Mutations in DOCK8 causes impaired binding of cytokines to the receptors. Management includes treatment of infections, supportive care and immunization. Recombinant human IFN-gamma, levamisole, ascorbic acid, rituximab have limited use [3]. These children need to be followed-up for infections and malignancies.
Conflict of Interest None. Source of Funding None.
References 1. Kline MW. Review of recurrent bacterial meningitis. Pediatr Infect Dis J. 1989;8:630–4. 2. Grimbacher B, Holland SM, Puck JM. Hyper-IgE syndromes. Immunol Rev. 2005;203:244–50. 3. Erlewyn- Lajeunesse MD. Hyper immunoglobulin-E syndrome with recurrent infection: a review current opinion and treatment. Pediatr Allergy Immunol. 2004;11:133–41. 4. Hsu AP, Davis J, Puck JM, Holland SM, Freeman AF. Autosomal dominant hyper IgE syndrome. 2010 Feb 23 [Updated 2012 Jun 7]. In: Pagon RA, Adam MP, Bird TD, et al., editors. Gene Reviews™ Internet]. Seattle (WA): University of Washington, Seattle; 1993– 2014. Available from: http://www.ncbi.nlm.nih.gov/books/ NBK25507 5. Moin M, Farhoudi A, Movahedi M, Rezaei N, Pourpak Z, Yeganeh M, et al. The clinical and laboratory survey of Iranian patients with hyperIgE syndrome. Scand J Infect Dis. 2006;38:898–903.
