1. Rheumatic manifestations of
primary immunodeficiencies in
children

2. • 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

3. • 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.

4. • 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.

6. 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.

7. 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)

8. • Most common presentation:
Monoarthritis or oligoarthritis
Treatment
1. S. aureus : Vancomycin
2. Mycoplasma : Tetracycline
3. Other organisms: Third-generation
cephalosporin

9. 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

10. • Intravenous immunoglobulin is effective in
most cases.
• Tumour necrosis factor-α receptor antagonist,
etanercept, has also been found efficacious in
CVIDs.

12. 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.

13. • 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).

14. • 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.

15. • 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

16. • 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.

17. 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.

18. 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.

19. 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.