Disturbances of immune system

1. Disturbances of immune system Case reports Prof.J. Hanacek, MD, PhD

2. Example No 1 Kas 19-1E: Patient with dyspnoe (bronchospasm) and mucosal inflammation Patient F.C., 25 years old, painter, has complaints to shortness of breath, with wheezing, water rhinorhea and swelling of the eyelids. Family history: His mother is treated for pollen allergy for many years. Personal history: He wasn’t seriously sick. He is smoker (10 years 10 cigarettes per day). He doesn’t sleep in feather pillow; no animals are present in his house. But he suffers from allergy to cat; he sneezed during the contact with any cat. He has no allergy to drugs, food and insect sting. He has no regular medication. Now, symptoms are recently - from March to April more intensive (serous nasal secretion, swelling of the eyelids, itching and conjunctivitis). He has dyspnoe after when supine, he describes "wheezing" and dry cough. 3 year ago, he was tested for allergy, the sensitization to birch pollen, cat and house dust mite was found. He refused any treatment.

3. On physical examination: eutrophic, swelling of the eyelids, conjunctivitis serous rhinitis, alveolar breathing with wheezing, puls rate 68/min., BP 125/80. Biochemistry: normal findings. Blood count - peripheral blood eosinophil percentage 14. Pulmonary function tests: VC 94,9%, FVC 87,6% FEV1 76,1%, PEF 64,3 %. Questions: • What type of disturbed immunity is manifested in this patient? • What are symptoms typical for? • What is the pathophysiological mechanism of breathlessness and mucosal changes? • What is the diagnosis?

4. Example No 2 Kas 19-4E: Anaphylaxis A 69-year-old woman was fit and well until one August when she was stung on the back of her right hand by a wasp. She had previously been stung on several occasions, the last time 2 weeks earlier. Within 5 min, she felt faint, followed shortly by a pounding sensation in her head and tightness of her chest. She collapsed and lost consciousness and, according to her husband, became grey and made gasping sounds. After 2-3min, she regained awareness but lost consciousness immediately when her husband and a friend tried to help her to her feet. Fortunately, a doctor neighbour arrived in time to prevent her being propped up in a chair: he laid her flat, administered intramuscular epinephrine (adrenaline) and intravenous antihistamines and ordered an ambulance. She had recovered fully by the next day.

5. Lab. Investigation: Total serum IgE was 147 IU/ml (N < 100iu/ml). Her antigen-specific IgEantibodylevel to wasp venom was 21 U/ml (RAST class 4) but that to bee venom was 0.3U/ml (RAST class 0). The skin test (Skin prick test) using standardized venom extract was positive at concentration 10 ug/ml of wasp venom. The patient was a candidate for specific allergen injection immunotherapy (vaccination) for her wasp venom anaphylaxis. The slight but definite risk of vaccination was explained and balanced against the major risk of anaphylaxis should she be stung again. The first injection consisted of 0.1ml of 0.0001µg/ml of wasp venom vaccine given subcutaneously. No reaction severe occurred, but some local raction occured for several times. Over the next 12 weeks, gradually increasing doses were given without adverse effects. Over this period, she tolerated injections of 100µg venom. She then continued on a maintenance regimen of 100µg of venom per month for 3 years.

6. Questions: • What is the pathogenesis of anaphylaxis? • What was the major mistake in the first aid? • What is the first drug of choice and why in treatment of anaphylaxis? • What is the mechanism of allergen vaccination (hyposensitization) • What is the expected outcome of this disease management?

7. Example No 3 Kas 19-8E: Tachycardia, weight loss, heat intolerance 34-year-old woman was admitted to the hospital because of tachycardia. Personal history: Followed by the endocrinologist 10 years ago for a disease of thyroid gland. She was doing well and that’s why she stopped the regular visits and the medications. Current complains: She does not feel well for a couple of months. She complains on heat intolerance and sweating. She gets readily tired, she can hardly concentrate. She observes accelerated hair-loss. She complains ondiarrhea and weight-loss of 7 kg in the last year. She often feels the palpitations and occasionally the heart-rate reaching 120/min. The symptoms are moreintensive in the last days and that’s why shevisited her GP.

8. Examination: • BP 120/55 mmHg, PR 118/min, BT 36,7°C. • Sweaty, thin-bodied. • Thin hair, exophtalmus. • Goiter, discrete murmur. • Heart sounds regular, discrete systolic murmur on aortal valve. Laboratory findings: • Na 140, K 4.1, Cl 102, bilirubin 18, ALT 0.74, AST 0.63, urea 6,2, creatinine 81, glucose 8.4, cholesterol 2.7, TSH 0.002. • Blood counts: normal values • Urine analysis: normal values • Chest X-ray: normal • ECG: sinus tachycardia, otherwise normal curve. Questions: • What type of disease could cause these symptoms and findings? • Can you describe the immunopathology in this case? • Do you expect suspicion or diagnosis of other immunopathology disease and why?

9. Example No 4 Kas 19-9E: Fever and joint pain 48-year-old woman was admitted to the hospital because of fever and joint pain. Personal history: Frequent tonsillitis in childhood, Hypertension,Type 2 diabetes mellitus Medicaments: Perindopril 2mg once a day Current complains: She has been treated by GP for 14 days for fever of unknown origin. She denied cough or dysuria. The infectious focus has never been found, however, antibiotics (claritromycin and doxycyclin afterwards) have been prescribed (with regard to ESR 80/90). The therapy did not have any effect she has continuously fever 38.1°C. She complains of joints pain as well. The proximal interphalangeal joints of both hands are usually swollen, reddish and hot.

10. On examination: • BP 150/80 mmHg, PR 90/min regular, BT 38.2°C • Sweaty, obese. • Swollen, reddish and hot proximal interphalangeal joints of both hands, palpations painful Laboratory findings: • FW: 90/100, CRP 90, • Na 143, K 4.2, Cl 103, bili 14, ALT 0.62, AST 0.55, urea 7.1, creatinine 90, glucose 7,9. • Blood counts: normal values • Urine analysis: normal values • Chest X-ray: normal • ECG: sinus tachycardia, otherwise normal curve. Questions: • What type of immune-pathology can you find? • What type of disease could cause the symptoms?

11. Example No 5 Kas 19-10: Celiac disease Patient A.B., eight years old girl, followed for diabetes mellitus type I. Family history: her mother is healthy; her father has diabetes mellitus type I. from age of 4 .Personal history: physiologic pregnancy, birth in term induced for mothers´ hypertension. Adaptation after the birth was good. At the age of five her parents found out she drank and passed urine in high amount and very frequently. She has been diagnosed with Diabetes mellitus type I. She was well compensated without ketoacidosis. A half year later diarrhea appeared very often and she failed to thrive Physical examination was normal.

12. Laboratory findings: Basic biochemistry was normal, blood count normal. IgE specific for the basic food allergens was negative, Anti-endomysial (AEA) andanti-tissue transglutaminase antibodies (a-tTG, (IgA isotype) were strongly positive. The endoscopic procedure was not successful. On physician recommendation parents introduced gluten-free diet. The diarrhea disappeared stoppedand girl did well. • Three month later the control laboratory test (AEA and a-tTG) checked again. Both antibodies were negative. • Parents ceased from respecting the physicians‘ recommendation and released the diet. In few days diarrhea and abdominal colic pain appeared again. The amount of AEA and a-tTG rapidly increased. After the re-introduction of gluten-free diet the laboratory tests dropped again and the girl felt well. Questions: • What are increased levels of AEA and a-tTG antibodies typical for? • What other symptoms may appear in the disease, • What are pathogenetic mechanisms of the disease? • What is the relationship of DM type I and celiac disease? • What type of diet is appropriate?