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Allergy/Immunology for the Internist

Allergy/Immunology for the Internist. Hien Nguyen Reeves, MD, ABAI, ABIM Clinical instructor UBC, Kelowna, BC. Disclosures. Grants/Research Support: None Speakers Bureau/Honoraria: Pfizer Canada, CME Speaker Schering-Plough Merck Pictures Dermatology Image Atlas. Learning Objectives.

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Allergy/Immunology for the Internist

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  1. Allergy/Immunology for the Internist Hien Nguyen Reeves, MD, ABAI, ABIM Clinical instructor UBC, Kelowna, BC

  2. Disclosures Grants/Research Support: • None Speakers Bureau/Honoraria: • Pfizer Canada, CME Speaker • Schering-Plough • Merck Pictures • Dermatology Image Atlas

  3. Learning Objectives After participating in this educational program, participants should be able to: 1. Describe the causes, signs, and symptoms of common allergic/immunologic conditions 2. Understand diagnostic tests for these conditions 3. Discuss the appropriate treatment of these conditions and long-term management of patients at-risk

  4. Mechanism of Hypersensitivity

  5. IgE hypersensitivity

  6. Angioedema of lips

  7. Angioedema of eyes

  8. Angioedema of hand

  9. Urticaria Cholinergic urticaria Typical urticaria

  10. Erythema marginatum Urticarial vasculitis

  11. Urticaria pigmentosa

  12. Serum sickness Morbilliform rash

  13. Erythema multiforme Dermatitis Herpetiformis

  14. Steven-Johnsons/TEN Bullous pemphigoid

  15. Case • 60 yo female presents with a 1 month history of persistent daily generalized rashes suggestive of hives. She reports episodes started when she was treated with Ciprofloxacin for a urinary tract infection. Within 1 week of taking the antibiotic, she developed this rash. She has since stopped the antibiotic but hives persist. Interestingly, she has had several episodes of lip and eye swelling as well as hives occurring intermittently over the past 10 years. Angioedema not necessarily associated with the hives. • She is taking over the counter antihistamines and oral prednisone but they have not controlled her rashes. She has avoided dairy and breads and has resorted to a bland diet of soups as she thinks foods may be causing her symptoms.

  16. Review of systems: Positive for chronic headaches, fatigue, heartburn, nausea, abdominal bloating, frequent upper respiratory infections (bronchitis, sinusitis, pneumonias, strep throats, and utis) and ”allergy” symptoms (rhinorrhea, watery eyes, nasal congestion all year round worse with scents) • PMH/PSH: HTN, GERD, Hypothyroidism, Hysterectomy, appendectomy, cholecystectomy, tonsillectomy • Social: ex-smoker 15 pk year, quit 10 years ago, marijuana use weekly, but no history of IVDU or other illicit drugs , drinks 1 glass of red wine daily, married for 30 years but husband just passed away. she is a retired teacher.

  17. Meds: Advil qd, Altace qd, Rabeprazole qd, Synthroid qd, ASA qd, prednisone 40 mg qd • Meds Allergies: Sulfa, Tetracycline, Cipro- rashes • FMH: Mother had emphysema and hypothyroidism, Father had HTN, CAD, MI at 65 yo, Sister with hypothyroidism, Brother healthy. No one with angioedema or infections in the family

  18. Problem List?

  19. Problem List • Generalized urticaria- Acute on chronic • Angioedema • Drug allergies • Recurrent infections • GERD, Abdominal bloating • Chronic fatigue • Chronic rhinorrhea • HTN • Thyroid dz

  20. Urticaria/angioedema definition • Urticaria-raised erythematous lesions involving superficial dermis, often generalized and pruritic, lasts minutes to hours, and can recur. Acute urticaria < 6 weeks, Chronic > 6 weeks. Multiple mechanisms-mast cells, basophils • Angioedema- self-limited nonpitting edema generally affecting the deeper layers of skin and mucous membranes. A result of increased vascular permeability causing the leakage of fluid into the skin in response to vasodilators released by immunologic mediators. 50% of pts with chronic urticaria are said to have angioedema - IgE, mast cells releasing histamines, leukotrienes, prostaglandins -Kinin and formation of bradykinin (vasodilator)

  21. Differential & Investigations?

  22. Classification of UrticariaAllergy, Asthma & Clinical Immunology 2011, 7(Suppl 1):S9 doi:10.1186/1710-1492-7-S1-S9

  23. Investigations • CBC, Creatinine, LFT, Ferritin • Urinalysis • Anti-thyroid peroxidase, anti-thyroglobulin antibodies • H.pylori serology, biopsy • CXR, CT sinus for chronic sinusitis • Skin test for environmental and food allergens-and ImmunoCap (RAST) to allergens if skin test not possible- to evaluate for atopy, poor PPV • Check IgG, IgA, IgM, IgE. • If IgG is low, then need to do IgG subclasses, antibody responses to vaccines- i.e.-pneumococcal, tetanus titers, HIB, CD markers (CD19, CD3, CD4, CD56). Hepatitis, MMR serology may be helpful

  24. Other studies • Serum electrophoresis , Hepatitis B and C serology, Monospot , antistreptolysin and anti-DNase • Stool samples for ova and parasite • TTG screening, PATCH testing if warranted • Serum tryptase

  25. C4, C1 esterase inhibitor (functional and qualitative) C1q, genetic testing for HAE • Drug testing- Penicillin skin testing, RAST to penicillin minor determinants. If need PCN, oral challenge or desensitization depending on history and risk of anaphylaxis. Other drugs not standardized. Desensitization has to be carried out every time. Testing and desensitization contraindicated in patients with a history of TEN/Stevens-Johnson s reaction to a drug • No sulfite testing • When in doubt, biopsy

  26. Flow diagram for angioedema

  27. Treatments for urticariaAllergy, Asthma & Clinical Immunology 2011, 7(Suppl 1):S9 doi:10.1186/1710-1492-7-S1-S9

  28. Cyclosporine • Low dose (3 mg/kg) cyclosporine (CsA) effective in treating patients with CIU in 13/19 (full remission) and 6/19 (significant relief) compared to controls over three months Toubi E et alAllergy 1997; 52: 312-6 • DBPC trial with 4mg/kg CsA revealed improvement in daily urticaria score (42 points max) by 12.7 (vs. 2.3 in placebo) • Histamine release decreased from 36% to 5% (p<0.0001) • Autologous skin test also reduced in responders Grattan CE et al.Br J Dermatol 2000; 143: 365-72

  29. Omilazumab- Xolair, anti-IgE

  30. Our patient results • UA-> 100,000 Staph, elevated anti-thyroid peroxidase abs > 1300, and positive H.pylori serology • Skin test negative to environmental and food allergens, IgE 330 IU/ml, IgG, IgA, IgM, CBC, LFT, Creatinine all wnl

  31. Case in question • Stopped ASA and ACEI, and switched to ARB • Treated H.pylori with triple therapy, and UTI • Angioedema and hives resolved • She takes Reactine and Ranitidine only as needed now, and off oral prednisone • Nasocorticosteroids, Atrovent nasal spray , nasal washes prn

  32. Key points • Through several mechanisms a variety of mediators may lead to urticaria or angioedema • Clinically, a causative agent is much more often identified in acute than in chronic urticaria/angioedema • A number of medications are available to control chronic urticaria while awaiting a spontaneous remission • Patients with angioedema without urticaria should be tested for C1 inhibitor deficiency • Recurrent infections, especially with other symptoms (rashes, alopecia, diarrhea) should be worked up for primary immunodeficiency

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