Rheumatic manifestations of primary immunodeficiencies in children

• Primary immunodeficiency disorders are classified according to the component of the immune system that is primarily involved.

• Primary immunodeficiency disorders (PIDs) are usually rare with a prevalence of 1:10,000 live births

• Defects in the adaptive immune responses include antibody deficiency syndromes and combined immunodeficiencies.

• Defects of innate immunity comprise disorders of phagocytes, toll-like receptor (TLR) mediated signalling and complement.

• The prime characteristic of a PID is an increased susceptibility to infections, but some forms can present with immune dysregulation leading to autoimmune and rheumatological illnesses.

Septic arthritides

Conditions associated with increased rate of septic arthritis :

1. Common variable immunodeficiency (CVID).2. X-linked agammaglobulinaemia.3. Chronic granulomatous disease (CGD).4. Wiskott–Aldrich syndrome.5. Interleukin-1 receptor-associated kinase-4

(IRAK-4) deficiency.

The organisms most commonly isolated from the joint :

1. Staphylococcus aureus (Most common).2. Streptococcus pneumoniae (Most common).3. Mycoplasma spp.(Antibody defects)4. Ureaplasma urealyticum.(Antibody defects)5. Enteroviruses.6. Pneumocystis jirovecii.7. Chlamydia pneumoniae (CVID)8. Adenovirus type 1 (CVID)

• Most common presentation: Monoarthritis or oligoarthritis Treatment1. S. aureus : Vancomycin2. Mycoplasma : Tetracycline3. Other organisms: Third-generation

cephalosporin

Aseptic arthritides

• Aseptic arthritis is the term used when no organism can be isolated from the synovial fluid or the synovial biopsy.

• Polyarthritis is the usual presentation.• Could be sequelae of recurrent bacterial and

parasitic infections in patients with PIDs or could be part of the autoimmune spectrum of disease associated with PIDs

• Intravenous immunoglobulin is effective in most cases.

• Tumour necrosis factor-α receptor antagonist, etanercept, has also been found efficacious in CVIDs.

Autoimmune manifestations

Autoimmune manifestations in complement deficiency :

1. Lupus-like illness presenting with rash and vasculitis ( C4 ,C2 deficiency)

2. The most effective screening test for complement defects is a CH50 assay.

3. Genetic deficiencies in the complement system are usually characterized by extremely low CH50 values.

• Most patients with primary C1q deficiency have systemic lupus erythematosus (SLE), an SLE-like syndrome without typical SLE serology, a chronic rash that has shown an underlying vasculitis on biopsy, or membranoproliferative glomerulonephritis (MPGN).

• Individuals with C1r, C1s, combined C1r/C1s, C4, C2, or C3 deficiency also have a high incidence of autoimmune syndromes, especially SLE or an SLE-like syndrome in which antinuclear antibody level is not elevated.

• Complete deficiency of only C4A, present in about 1% of the population, also predisposes to SLE, though C4 levels are only partially reduced.

• A few patients with C5, C6, C7, or C8 deficiency have SLE.

• Individuals with SLE and a complement defect generally respond as well to therapy as those without complement deficiency

• Henoch–Schonlein purpura( c4) , Dermatomyositis, scleroderma and vasculitis have also been reported with early complement deficiencies.

• Patients with defect in late complement component usually present with recurrent invasive infections due to encapsulated organisms.

Autoimmune manifestations in CVID• 1–3% patients with CVID may develop SLE.• In 67% patients, the SLE activity decreased,

apparently attributable to a significant loss of B cells leading to SLE remission.

• The IVIg is safe and ameliorates joint disease in these patients.

• Hydroxychloroquine is safe and modestly effective.

Autoimmune manifestations in IgA deficiency:

• Juvenile idiopathic arthritis (JIA) and SLE are known to occur in higher frequencies in patients with selective IgA deficiency.

• Arthritis resembling juvenile idiopathic arthritis is a common manifestation of PIDs, especially of XLA and Wiskott–Aldrich syndrome. Up to 30% patients with Wiskott–Aldrich syndrome may present with JIA-like disease.

Acute lymphoproliferative syndrome(ALPS).

1. Generalised chronic, non-malignant lymphadenopathy.

2. Hepatosplenomegaly.3. Hypergammaglobulinaemia.4. Autoimmune cytopaenias.5. Autoantibodies directed against erythrocytes

and platelets.• Clinically, the syndrome mimics systemic lupus.