ORGAN-SPECIFIC AUTOIMMUNE DISEASESProf Peter Gergely

ORGAN-SPECIFIC AUTOIMMUNE DISEASESProf Peter Gergely

Classification of organ-specific autoimmune diseases according to organ involvement1. ENDOCRINE SYSTEMthyroid: Hashimoto’s thyroiditis and primary (idiopathic)

myxedema, Graves’ disease and endocrine ophthalmopathy

parathyroid: hypoparathyroidismpancreas: Type 1 diabetes mellitus (insulin-dependent)adrenals: Addison’s diseasegonads: early menopausa, female infertility, azoospermiahypophysis: autoimmune hypophysitis (with hypofunction)Polyglandular autoimmune syndromes:Type I: Addison + hypoparathyreoidism + chr. mucocutan

candidiasisType II: Graves’ + Addison’ or T1DM or myastheniaPOEMS syndrome = polyneuropathia + organomegalia(hepatosplenomegalia) + endocrinopathia (hypogonadism) + M protein + skin alterations (hyperpigmentation)

Pathomechanism ofGraves’ disease

Exophthalmos in Graves’ disease

Lymphocytic infiltration in Hashimoto thyroiditis

Thyroid antibodies in Hashimoto’s thyroiditis:a) anti-microsomal antibody or anti-thyroid peroxidase (TPO)b) anti-thyroglobulin (anti-TG)

The odds ratio of developing hypothyroidism in individuals with positiveantibodies is 8 for females and 25 for males.

a b

Islet cell antibodies in Type 1 diabetes mellitus

2. DIGESTIVE SYSTEMmouth: aphtha, periodontitisstomach: chronic atrophic gastritis and pernicious anemia

intestines: gluten-sensitive enteropathia, chronic non-specificinflammatory bowel disease (IBD): ulcerative colitis andCrohn’s disease

liver: chronic autoimmune hepatitis (Type I, II), primarybiliary cirrhosis (PBC), primary sclerotizingcholangiitis

3. EYE sympathetic ophthalmia, phacogenic uveitis, Vogt-Koyanagi-Harada syndrome, endogenous or idiopathic uveitis

4. NERVOUS SYSTEMparainfectious encephalitis, idiopathic polyneuritisand/or Guillain-Barré syndrome, multiple sclerosis,myasthenia gravis

Autoantibodies in autoimmune liver diseases:a) antimitochondrial antibodies (AMA) in primary biliary cirrhosisb) smooth muscle antibodies (SMA) in autoimmune hepatitis

a b

a b

a) parietal cell antibodies in chronic autoimmune gastritis with perniciousanemia

b) antibodies to striated muscle (acetylcholine receptors) in myastheniagravis

5. HEART rheumatic fever, postinfarction syndrome,idiopathic (autoimmune) cardiomyopathies

6. KIDNEY anti-GBM nephritis or Goodpasture syndrome, idiopathic or primary glomerulonephritis,

amyloidosis

7. LUNG extrinsic allergic pneumonitis, eosinophilicpneumonia, idiopathic pulmonary fibrosis, sarcoidosis

8. SKIN vesicobullous skin diseases (pemphigus vulgaris, bullous pemphigoid, dermatitis herpetiformis, herpes gestationis), psoriasis, vitiligo, alopecia

a b

a) GBM antibodies in Goodpasture syndromeb) endomysium antibodies in linear IgA dermatosis – associated

with celiac disease

a b

a) Pemphigus vulgaris – antibodies against keratinocytes (desmoglein 3)b) Bullous pemphigoid – antibodies against skin basement membrane

Alopecia areata

Vitiligo

9. BLOODred blood cells: autoimmune hemolytic anaemia, drug-induced

immune-hemolytic anemia, isoimmunehemolytic anemia, autoimmune aplastic anemia,Diamond-Blackfan’s syndrome

thrombocyte: idiopathic (immune) thrombopenic purpura (ITP),drug-induced immune thrombocytopenia, post-transfusion purpura

granulocyte: immune neutropenia, drug-induced utoimmuneneutropenia

hemostasis: antiphospholipid syndrome (APS)

Immune thrombocytopenia (ITP). • A nonblanching, nonpalpable petechial rash in a patient with thrombocytopenia. • ITP is the most frequent cause of acquired thrombocytopenia in children. • It is caused by platelet destruction by autoantibodies. IgG antibodies are directed against platelet membrane glycoproteins (GPIIb/IIIa or GPIb/IX GP complexes). • An episode may be preceded by a viral infection.• Thrombocytopenia is not associated with significant lymphadenopathy and hepatosplenomegaly. Anemia and neutropenia are absent. • Approximately 80% to 90% of cases of acute ITP resolve without recurrence.• The estimated prevalence is 5-6/100,000.

Thrombocytopenia and large platelets in a patient with ITP. The increased platelet size is thought to reflect increased megakaryopoiesis. Giant platelets and thrombocytopenia are also observed in Bernard-Soulier syndrome, a hereditary bleeding disorder with defective platelet glycoprotein Ib/IX surface receptors

A normal or increased number of megakaryocytes in the bone marrow of patients with ITP. Megakaryocytes are easily identified as the largest cell type in the bone marrow and by their finely granular cytoplasm and multilobed nuclei. A low megakaryocyte count, decreased cellularity, and the presence of abnormal cells suggests a diagnosis other than ITP. In typical cases of ITP, a bone marrow aspirate is not mandatory

Therapy of ITP

• In persons with acute ITP, splenectomy usually results in rapid, complete, and lifelong clinical remission.

• In persons with chronic ITP, the results of splenectomy are typically less predictable than they are in patients with acute ITP. Platelet counts may not fully revert to normal values, and relapses are not uncommon.

• For initial (induction) treatment (platelet count <20 X 109/L [<20 X 103/mL]), one regimen is prednisolone 1.0 mg/kg/d with the intent of a rapid and complete taper in 7-10 days or as soon as possible thereafter

• IVIG (0.4-1 mg/kg)• No evidence based therapy for chronic forms. Possibilities:

a) rituximabb) cytostatics (azathioprin, vincristin), cyclosporin Ac) danazol