Immunoglobulin replacement therapy reduces chronic rhinosinusitis in patients with antibody deficiency.

BACKGROUND: Patients with primary antibody deficiencies have an increased frequency of sinonasal and pulmonary infections. Immunoglobulin (Ig) replacement is a standard therapy for common variable immunodeficiency (CVID) and other antibody deficiency diseases. Although there is convincing evidence that Ig replacement reduces pulmonary infections, there is little evidence that it reduces sinus infections or abates chronic rhinosinusitis (CRS). This study aims to identify the impact of Ig replacement on CRS in antibody deficiencies. METHODS: A single-center, retrospective chart review of adult patients from 1995 to 2015 was performed. Inclusion criteria were diagnosis of CVID or specific antibody deficiency (SAD), history of CRS requiring medical and/or surgical management within the year prior to presentation, treatment with Ig replacement therapy, and follow-up interval of at least 1 year after initiating Ig replacement. Patients with secondary immune deficiencies were excluded. Thirty-one patients met criteria. Data collected included pretreatment and posttreatment Lund-Mackay scores, and frequency of sinusitis and pulmonary infections requiring rescue antibiotics. Statistical analysis was performed using Wilcoxon signed-rank tests. RESULTS: A significant decline in the Lund-Mackay score was evidenced from pretreatment to posttreatment (p < 0.01). Treatment also resulted in significantly lower rates of sinusitis (p < 0.01) and pulmonary infections (p < 0.01). Additionally, 56% of patients who were on prophylactic antibiotics prior to Ig replacement were able to discontinue their use. CONCLUSION: We present objective evidence showing that Ig replacement therapy has a positive impact on the frequency of sinusitis and confirm its positive impact on pulmonary infections in adult patients with CVID and SAD.

Neuromyelitis optica-IgG+ optic neuritis associated with celiac disease and dysgammaglobulinemia: a role for tacrolimus?

We present a pediatric case of recurrent optic neuritis, celiac disease, partial IgA and IgG3 deficiency in the context of anti-aquaporin-4 auto-immunity and familial IgA deficiency with celiac disease. Treatment with tacrolimus was successful in preventing disease relapses. This case stresses the relevance of central nervous system anti-aquaporin-4 auto-immunity in a broader context of immune dysregulation and neuro-immunology.

Selective immunoglobulin M deficiency presenting with recurrent impetigo: a case report and review of the literature.

Selective immunoglobulin M (IgM) deficiency is a rare disorder defined by a decreased serum level of IgM and normal levels of other immunoglobulin classes. The disease has not been well described and the cause remains unknown. Patients with IgM deficiency may present with a wide spectrum of clinical manifestations, from asymptomatic to life-threatening infections, including recurrent respiratory and gastrointestinal infections, allergy and autoimmunity. Here, we report a 6.5-year-old otherwise healthy boy with selective IgM deficiency who presented with multiple recurrent impetigo. We reviewed the published data regarding selective deficiency of IgM.

Replacement IgG therapy and self-therapy at home improve the health-related quality of life in patients with primary antibody deficiencies.

PURPOSE OF REVIEW: This article describes the health-related quality of life and health of patients suffering from primary antibody deficiencies before and after the initiation of lifelong IgG replacement therapy, and before and after the introduction of home-therapy regime programmes. The importance of including patient-reported or parent-reported outcomes in evaluations of treatment and care of this group of patients is also discussed. RECENT FINDINGS: Recently diagnosed adults suffering from primary antibody deficiencies and not yet on IgG therapy report poor health and poor health-related quality of life as compared with healthy individuals. Weekly subcutaneous IgG infusions (100 mg/kg) significantly improve health and normalize health-related quality of life. IgG self-infusions at home further improve the self-reported health and health-related quality of life of both adults and children. Being able to self-infuse at home instead of visiting the hospital two to four times per month has been shown to increase the treatment satisfaction of both adult patients and their families, and to result in increased flexibility, independence and sense of self-control. SUMMARY: Adequate IgG replacement therapy means a dramatically improved life situation. Home-therapy programmes should be encouraged, as self-infusions at home further improve health-related quality of life and self-perceived health.

Inflammatory and autoimmune complications of common variable immune deficiency.

Common variable immune deficiency (CVID) is associated with autoimmune and inflammatory complications in addition to recurrent infections. The most common conditions are idiopathic thrombocytopenia purpura, autoimmune hemolytic anemia, sarcoid-like granulomatous disease and gastrointestinal inflammation. IVIG administration reduces the frequency of infections, but does not always prevent autoimmunity or inflammation. TNF antagonists and anti-CD20 immunomodulators have shown some efficacy in CVID in a few patients; further controlled studies are needed to determine the best management of these conditions in the setting of immunodeficiency.

[Therapeutic indications of intravenous immunoglobulins]. / Les indications thérapeutiques des immunoglobulines intraveineuses.

Intravenous Immunoglobulin (IVIg) provide a wide spectrum of antibody specificities in patients with antibody deficiencies and restore immune homeostasis in patients with auto-immune diseases. Controlled trials have now been performed in a large number of diseases: in primary and secondary antibody deficiencies, auto-immune neurological diseases and various other auto-immune or systemic inflammatory conditions. Mechanisms of action of IVIg are multiple and often associated for a given disease. These mechanisms are however incompletely understood and therapeutic effect of IVIg remains to be investigated in a wide range of diseases.

[Gammaglobulin preparations used for treatment of primary humoral immunodeficiencies]. / Preparaty gammaglobulin stosowane w leczeniu substytucyjnym wrodzonych niedoborów odpornosci humoralnej.

In the review safety and efficacy of substitution therapy in patients with predominant antibodies immunodeficiencies were presented. Differences between intravenous gammaglobulin preparation has been performed.

Immunodeficiency presenting as hypergammaglobulinaemia with IgG2 subclass deficiency.

Recurrent bacterial infections, lymphadenopathy, and failure to thrive are unlikely to be attributed to immune deficiency if they occur in the presence of hypergammaglobulinaemia, and other explanations will usually be sought. We describe eight patients who presented with all these features in infancy or early childhood. Deficiencies of immunoglobulin and antibody production were initially discounted, and the children were referred for investigation of possible lymphoma, autoimmune disease, or chronic viral infection. The patients were later referred to us for more detailed immunological investigation, which revealed low levels of IgG2 and poor specific antibody production to common pathogens. Treatment with intravenous immunoglobulin resulted in resolution of signs and symptoms in all patients. Thus we have shown that hypergammaglobulinaemia does not preclude the presence of immunoglobulin/antibody deficiency. We suggest that investigation of children with high levels of IgG and features of immunodeficiency should include IgG subclass analysis.

Dysgammaglobulinemia in steroid-dependent optic neuritis: response to gammaglobulin treatment.

At the age of 12, a prematurely born boy with an otherwise unremarkable past medical history developed bilateral optic neuritis associated with transverse myelopathy. Over the ensuing 3 years, recurrent bouts of optic neuritis OU, with dyschromatopsia, and acuity and field loss (arcuate, central, and paracentral scotomas) were controlled with increasing doses of corticosteroids. However, the patient became steroid-dependent and experienced recurrent optic neuritis during multiple attempts at tapering the steroids. He developed optic atrophy and steroid complications, including cushingnoid features and growth maturation delay. Immunoglobulin G subclass 2 and 3 deficiencies were the only serologically detectable abnormalities. Administration of intravenous gammaglobulin (25 g monthly) allowed discontinuation of steroids without further ophthalmic or neurologic disease. Following steroid withdrawal and institution of gammaglobulin, the patient grew 6 inches within 2 years, regaining his vision, retrieving his stature, and normalizing his psychosocial development.

Childhood eosinophilic fasciitis presenting as inflammatory polyarthritis and associated with selective IgA deficiency.

A 13 year old school boy presented with seronegative inflammatory polyarthritis after a flu-like illness. Four months later clinical features of eosinophilic fasciitis became apparent. After histological diagnosis treatment was started with prednisone 40 mg daily, with a good response. Routine investigations showed persistent selective IgA deficiency.

Bacterial overgrowth after high-dose corticosteroid treatment.

A 63-year-old man with systemic lupus erythematosus and selective IgA deficiency developed intractable diarrhoea the day after treatment with prednisone, 50 mg daily, was started. The diarrhoea was considered to be caused by bacterial overgrowth and was later successfully treated with doxycycline. Although IgA deficiency is a risk factor for bacterial overgrowth, a further predisposing condition is necessary for development of this disorder but was not present in this case. We therefore suppose that high-dose treatment with corticosteroids might be a hitherto undescribed risk factor for bacterial overgrowth in vulnerable patients.

Thymopentin treatment of selective IgA deficiency.

Thymic hormones have been shown to modulate immunoglobulin production in a number of experiments and it is generally agreed that this action is mediated by modulation of helper and/or suppressor T cell activities. The possibility of upregulating the immunoglobulins is of particular relevance in patients with hypogammaglobulinemias and this paper reports on the results of thymopentin treatment in 9 patients with selective IgA deficiency. Two out of 4 patients responded positively in an open-label trial; in one the serum IgA values remained stable up to 8 weeks after discontinuation of treatment whereas there was a rapid fall in the other. Both responders had consistently normal T4/T8 ratios during the treatment, whereas the nonresponders revealed high ratios with large fluctuations of the T4/T8 ratio. In a subsequent (still ongoing) double-blind trial in 5 patients (3 thymopentin, 2 placebo) no significant change of serum or secretory IgA levels has been observed. Taken together, the data suggest that the tested dose regimen of thymopentin (i.e. daily i.m. injections of 1 mg/kg for 2 weeks, then same dose 3 time weekly for 10 weeks) may only work in a subset of patients with selective IgA deficiency. In the present study we did not attempt to distinguish to which of the three known subgroups the 9 patients belonged, nor did we try alternative dose regimens of thymopentin.

Tremor as a feature of chronic relapsing and dysgammaglobulinemic polyneuropathies. Incidence and management.

Seven patients with chronic relapsing polyneuropathy and four patients with dysgammaglobulinemic polyneuropathy had tremor during the course of their illness. The tremor was coarse, irregular, and unrelated to proprioception loss, muscle weakness, or fatigue; it appeared to represent disease activity or an early sign of a new relapse. None of these patients had clinical signs of CNS disease or family history of essential tremor. The tremor in all seven patients with relapsing neuropathy and in one of the three treated patients with dysgammaglobulinemia responded to immunosuppressive drugs that controlled the underlying immune mechanism(s) of the disease. In two patients with dysgammaglobulinemic polyneuropathy, the tremor improved with propranolol hydrochloride.