Hyper–IgE syndrome (previously known as Job’s syndrome) is a complex disorder characterized by extreme elevation of serum IgE level, chronic dermatitis, repeated lung and skin infection, atopic dermatitis [Citation1] and staphylococcal pneumatoceles [Citation2]. Patients are at increased risk of osteoporosis and spontaneous bone fracture [Citation1]. Ulceration is also frequently present and lymphadenopathy may be complicated by lymph nods abscess [Citation2].
Non-immunological features of the condition include coarse facies with a wide nasal bridge, large head, joint laxity and a high incidence of scoliosis [Citation2]. After the newborn period, skin findings include retroauricular fissure, external otitis, infected dermatitis of axilla and groin, and folliculitis of the upper back and shoulder [Citation1].
Peripheral blood lymphocyte subsets are generally normal and no consistent abnormality of T cells has yet been identified [Citation3]. In a significant proportion of patients there is a failure of antibody response to polysaccharide antigens, which contributes to the susceptibility to infection [Citation2]. Patients are not neutropenic and their neutrophils ingest and kill bacteria normally. However, neutrophil chemotaxis is reduced and it has been shown that mononuclear cells from hyper-IgE patients produce a factor that is inhibitory to neutrophil chemotaxis [Citation3].
The mainstay of treatment is long term anti-staphylococcal antibiotic prophylaxis [Citation1]. Intravenous Immunoglobulin (IVIG), which is an expensive treatment modality, is also employed successfully for the treatment of this illness [Citation5]. Severe cases may need bone marrow transplantation [Citation1].
Cimetidine is often given to those who respond poorly to antibiotics alone, for its stimulatory effects on neutrophil chemotaxis [Citation1, Citation6] Recently, Feily et al. speculated the potential efficacy of L-carnitin, which enhances PMN motility, for treatment of this order [Citation1].
Methisoprinol (active substance: isoprinosine [ISO]) is a form of inosine that acts as a stimulator of the immune system. It is currently under investigation for use in cancer therapy, in the treatment of herpes virus and rhinovirus infections, and in immune restoration in pre-AIDS patients.[Citation7] It has been shown that ISO restored lymphocyte proliferation, NK activity, and neutrophil chemotaxis to normal or near normal levels in aging humans [Citation8]. Methisopronin antagonizes the serum-inhibiting activity present in the sera of patients affected by immunoproliferative diseases (Hodgkin’s disease and multiple myeloma), and causes a significant recovery of this leukocyte function [Citation9].
Furthermore, it stimulates lymphocytes and monocytes to produce substances that activate neutrophil chemotaxis [Citation10]. ISO also appears to potentiate the production of interleukin 1 and interleukin 2 in cultures of lipopolysaccharide stimulated human monocytes and phytohemagglutinin stimulated cultures of blood mononuclear cells, respectively, at pharmacological drug levels. It also enhances immunoglobulin production consistent with inhibition of suppressor cell activity or stimulation of helper activity [Citation11]. In sum, therefore, given the safety of methisoprinol we suggest that our colleagues consider methisopronil treatment with a patient suffering from Hyper IgE syndrome.
References
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- Grimbacher B, Holland SM, Gallin JI et al. Hyper IgE syndrome with recurrent infections—an autosomal dominant multisystem disorder. N Eng J Med 1999;340:692–702.
- Donabedian H, Gallin JI. Two inhibitors of neutrophil chemotaxis are produced by hyper immunoglobulin E-recurrent infection syndrome mononuclear cells exposed to head-killed staphylococci. Infect Immune 1983;40:1030–7.
- Aihara Y, Mori M, Yokota S. Successful treatment of onychomycosis with fluconazole in two patients with hyperimmunoglobulinemia E syndrome. Pediatr Dermatol 1996;13:493–5.
- Gennery AR, Flood TJ, Abinun M, Cant AJ. Bone marrow transplantation does not correct the hyper IgE syndrome. Bone Marrow Transplant 2000;25:1303–5.
- Sanal O, Göçmen A, Tezcan I, Ersoy F, Adalioğlu G. Hyper-IgE syndrome: a case report. Turk J Pediatr 1990 Oct–Dec;32(4):273–8.
- http://medical-dictionary.thefreedictionary.com/inosiplex. Accessed 23 May 2009.
- Tsang KY, Pan JF, Swanger DL, Fudenberg HH. In vitro restoration of immune responses in aging humans by isoprinosine. Int J Immunopharmacol. 1985;7(2):199–206.
- Azzarà A, Polidori R, Petrini M, Margelli M, Vatteroni ML, Grassi B, et al. Methisoprinol restoration of leukocyte chemotaxis inhibition by blocking factors in immunoproliferative diseases. Int J Tissue React 1984;6(4):303–10.
- Ricevuti G, Mazzone A, Baiguera R [Effect of methisoprinol on neutrophil functions in patients with rheumatoid arthritis. Minerva Med. 1985 Oct 27;76(41):1945–50.
- Hersey P, Bindon C, Bradley M, Hasic E. Effect of Isoprinosine on interleukin 1 and 2 production and on suppressor cell activity in pokeweed mitogen stimulated cultures of B and T cells. Int J Immunopharmacol 1984;6(4):321–8.