ORGAN-SPECIFIC AUTOIMMUNE DISEASES Prof Peter Gergely ORGAN-SPECIFIC AUTOIMMUNE DISEASES Prof Peter Gergely Classification of organ-specific autoimmune diseases according to organ involvement 1. ENDOCRINE SYSTEM thyroid:Hashimoto’s thyroiditis and primary (idiopathic) myxedema, Graves’ disease and endocrine ophthalmopathy parathyroid:hypoparathyroidism pancreas:Type 1 diabetes mellitus (insulin-dependent) adrenals:Addison’s disease gonads:early menopausa, female infertility, azoospermia hypophysis:autoimmune hypophysitis (with hypofunction) Polyglandular autoimmune syndromes: Type I: Addison + hypoparathyreoidism + chr. mucocutan candidiasis Type II: Graves’ + Addison’ or T1DM or myasthenia POEMS syndrome = polyneuropathia + organomegalia(hepatosplenomegalia) + endocrinopathia (hypogonadism) + M protein + skin alterations (hyperpigmentation) ORGAN-SPECIFIC AUTOIMMUNE DISEASES

Pathomechanism of Graves’ disease Pathomechanism of Graves’ 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 positive antibodies is 8 for females and 25 for males. a b Thyroid antibodies in Hashimoto’s thyroiditis:

Islet cell antibodies in Type 1 diabetes mellitus

2. DIGESTIVE SYSTEM mouth:aphtha, periodontitis stomach:chronic atrophic gastritis and pernicious anemia intestines:gluten-sensitive enteropathia, chronic non-specific inflammatory bowel disease (IBD): ulcerative colitis and Crohn’s disease liver:chronic autoimmune hepatitis (Type I, II), primary biliary cirrhosis (PBC), primary sclerotizing cholangiitis 3. EYEsympathetic ophthalmia, phacogenic uveitis, Vogt-Koyanagi-Harada syndrome, endogenous or idiopathic uveitis 4. NERVOUS SYSTEM parainfectious encephalitis, idiopathic polyneuritis and/or Guillain-Barré syndrome, multiple sclerosis, myasthenia gravis 2. DIGESTIVE SYSTEM

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

ab a) parietal cell antibodies in chronic autoimmune gastritis with pernicious anemia b) antibodies to striated muscle (acetylcholine receptors) in myasthenia gravis parietal cell antibodies in chronic autoimmune gastritis with pernicious anemia

5. HEART rheumatic fever, postinfarction syndrome, idiopathic (autoimmune) cardiomyopathies 6. KIDNEYanti-GBM nephritis or Goodpasture syndrome, idiopathic or primary glomerulonephritis, amyloidosis 7. LUNGextrinsic allergic pneumonitis, eosinophilic pneumonia, idiopathic pulmonary fibrosis, sarcoidosis 8. SKINvesicobullous skin diseases (pemphigus vulgaris, bullous pemphigoid, dermatitis herpetiformis, herpes gestationis), psoriasis, vitiligo, alopecia 5. HEART

ab a)GBM antibodies in Goodpasture syndrome b)endomysium antibodies in linear IgA dermatosis – associated with celiac disease GBM antibodies in Goodpasture syndrome

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

Alopecia areata Vitiligo Alopecia areata

9. BLOOD red blood cells: autoimmune hemolytic anaemia, drug-induced immune-hemolytic anemia, isoimmune hemolytic 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 utoimmune neutropenia hemostasis:antiphospholipid syndrome (APS) 9. BLOOD

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. Immune thrombocytopenia (ITP).

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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 Thrombocytopenia and large platelets in a patient with ITP

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 A normal or increased number of megakaryocytes in the bone marrow of patients with ITP

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 10 9 /L [<20 X 10 3 /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) rituximab b) cytostatics (azathioprin, vincristin), cyclosporin A c) danazol