Practical class Alergollogy and Clinical Immunology

Lucrari practiceAlergologie si ImunologieDr. Vasile FeldrihanCazul 1 Pacienta 26 ani, - artralgii, redoare matinala articulatiile mici ale mainii (MCF), debut 2 luni - debut insidios - stare generala alterata, astenie de aprox 6 luniAHC: nesemnificativeAPP: nesemnificativC v+m: medic stomatologthe pain and stiffness are significantly worse in the morning and may improve with gentle activity.2Examen clinic

The joints are usually warm and tender with some jointswelling.small joints of both hands with spindling of the fingers.3Investigatii paracliniceVSH: 20-50 mm/h (normal:0-10mm/h), CRP>6 (n.r.10 UI/ml - pozitiv)ANA: 1:100 (negativ 1 ora artrita > 3 articulatii simultan > 6 saptamani artrita art mici ale mainii artrita simetrica noduli subcutanati FRmodificari RX (eroziuni, osteopenie)

ARTRITA REUMATOIDA Afectiune autoimuna, afectare poliarticulara simetrica, manifestari sistemice Evolutie variabilaFactorul Reumatoid autoAc circulanti tinta antigenica Fc IgG RFs arFormeaza complexe imune ce activeaza complementul si induc inflamatie sinovita cronica

. Transient production of RFs is an essential part of the bodys normal mechanism for removing immune complexes, but in RA they show a much higher affinity and their production is persistent and occurs in the joints. They are of any immunoglobulin class (IgM, IgG or IgA), but the most common tests employed clinically detect IgM rheumatoid factor. 8Factorul reumatoid Aprox 70% x AR = seropozitivi ; titrul pozitiv poate preceda debutul clinicFormele seronegative tind sa asocieze o evolutie clinica usoara ! FR nu este test diagnostic, absenta nu exclude boala. Transient production of RFs is an essential part of the bodys normal mechanism for removing immune complexes, but in RA they show a much higher affinity and their production is persistent and occurs in the joints. They are of any immunoglobulin class (IgM, IgG or IgA), but the most common tests employed clinically detect IgM rheumatoid factor. ; however, it is a useful predictor of prognosis. A persistently high titre in early disease implies more persistently active synovitis, more joint damage and greater disability eventually, and justifies earlier use of DMARDs.

9Anti-CCP diagnostic precoce de boala, inaintea debutului clinic- indica progresia si severitatea afectarii articulare

ANA pozitivSystemic lupus erythematosus 95Systemic sclerosis 70Sjgrens syndrome 80Polymyositis and dermatomyositis 40Rheumatoid arthritis 30Other diseasesAutoimmune hepatitis 100Drug-induced lupus > 95Myasthenia gravis 50Diabetes mellitus 25Infectious mononucleosis 510Normal population 8Management Diagnostic precoce - esentialTerapie:- Simptomatica : AINS, corticoterapie - DMARD patogenica: medicamente antireumatice reduc inflamatia, inhiba sint citok proinflamatoare, impact favorabil clinic si paraclinic amelioreaza simptomatologia si sdr inflamator (sulfasalazina, leflunomide, methotrexat, agenti biologici)The doctor and therapist should retain a positive approach and remind the patient that with the help of drugs most will continue to lead a more or less normal life despite their arthritis; 25% will recover completely. The earliest years are often the most difficult and people should be helped andencouraged to stay at work during this phase if possible.A poor prognosis is indicated by: A clinical picture of an insidious rather than an explosiveonset of RA, female sex, increasing number ofperipheral joints involved and the level of disability atthe onset. Blood tests showing a high CRP/ESR, normochromicnormocytic anaemia and high titres of anti-CCPantibodies and of rheumatoid factor. X-rays with early erosive damage (N.B. ultrasound andMRI can show cartilage and bone damage prior toconventional X-rays).Prognosis can be altered dramatically with early DMARDtherapy under expert supervision12Reactii adversehiperglicemie, rezistenta la insulina, DZosteoporozacataractadepresie, psihozacolita, ulcer gastricHTAhipogonadism, amenoree, sterilitateretinopatiesdr Cushinginfectii oportunisteatrofie cutanataWide range of side effects:

13inapoi la caz AINSDMARDs - Methotrexat and Sulfasalazina nu au ameliorat simptomatologia

ImmunologyMany factors have been implicated but the chronic synovial inflammation is caused by ongoing T cell activation. The presence of activated T cells and macrophages and local production of rheumatoid factor autoantibodies in the joint in RA suggests that immune dysregulation plays a fundamental role in pathogenesis. Anti-CCP (anti-citrullinated cyclic peptide) antibodies react with proteins where arginine has been replaced by citrulline. CCPs predate the clinical disease by several years. They help distinguish early RA from transient polyarthritis.The TNF superfamily of cytokines produced mainly by activated macrophages and T cells play a role in the development of joint inflammation. Antibodies to TNF-, IL-1 or specific blocking agents produce marked shortterm improvement in synovitis, indicating the pivotal role of these cytokines in the chronic synovitis. They also reduce the malaise and tiredness felt in active RA.15Cazul 2

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erythematous nonpruritic skin rash located on the face, and sun exposed areas (hands) onset during the previous week, which she spent playing in the garden

18Diagnostic? LES - criterii de diagnostic -Rash malar

(butterfly rash) - Classical feature is the malar: often precipitated by sunlight. It is erythematous and may be raised and pruritic. It spares the naso-labial folds20LES2. Lupus discoid

It tends to occur in sun-exposed areas. It is erythematous, well demarcated and associated with scaling:21LES3. Fotosensibilitate 4. Ulceratii orale/nazale5. Artrita sedii mici6. Serozita 7. Afectare renala8. Afectare neurologica9. Afectare hematologica:anemie, leucopenie, trombocitopenie10. Sdr disimunitar: anti-ADNdc, anti-Sm, antifosfolipidici11. ANA

22.inapoi la cazInvestigatii paraclinice?Investigatii de laboratorANA: 1:320 (negativ