Allergy/Immunology for the Internist

Allergy/Immunology for the InternistHien Nguyen Reeves, MD, ABAI, ABIMClinical instructor UBC, Kelowna, BC1DisclosuresGrants/Research Support: NoneSpeakers Bureau/Honoraria: Pfizer Canada, CME SpeakerSchering-PloughMerck

PicturesDermatology Image Atlas

2Learning ObjectivesAfter participating in this educational program, participants should be able to:1. Describe the causes, signs, and symptoms of common allergic/immunologic conditions2. Understand diagnostic tests for these conditions3. Discuss the appropriate treatment of these conditions and long-term management of patients at-risk

3Mechanism of Hypersensitivity

4IgE hypersensitivity

5Angioedema of lips

6Angioedema of eyes

7Angioedema of hand

8Urticaria Cholinergic urticariaTypical urticaria

9Erythema marginatumUrticarial vasculitis

10Urticaria pigmentosa

11Serum sicknessMorbilliform rash

12Erythema multiformeDermatitis Herpetiformis

13Steven-Johnsons/TENBullous pemphigoid

14Case60 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.

15Review 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, tonsillectomySocial: 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.

16Meds: Advil qd, Altace qd, Rabeprazole qd, Synthroid qd, ASA qd, prednisone 40 mg qdMeds Allergies: Sulfa, Tetracycline, Cipro- rashesFMH: 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

17Problem List?18Problem ListGeneralized urticaria- Acute on chronicAngioedemaDrug allergiesRecurrent infectionsGERD, Abdominal bloatingChronic fatigueChronic rhinorrheaHTNThyroid dz

19Urticaria/angioedema definitionUrticaria-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, basophilsAngioedema- 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)20Differential & Investigations?Classification of UrticariaAllergy, Asthma & Clinical Immunology 2011, 7(Suppl 1):S9 doi:10.1186/1710-1492-7-S1-S9

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InvestigationsCBC, Creatinine, LFT, FerritinUrinalysisAnti-thyroid peroxidase, anti-thyroglobulin antibodiesH.pylori serology, biopsyCXR, CT sinus for chronic sinusitisSkin test for environmental and food allergens-and ImmunoCap (RAST) to allergens if skin test not possible- to evaluate for atopy, poor PPVCheck 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

26Other studiesSerum electrophoresis , Hepatitis B and C serology, Monospot , antistreptolysin and anti-DNaseStool samples for ova and parasiteTTG screening, PATCH testing if warrantedSerum tryptase

27C4, C1 esterase inhibitor (functional and qualitative) C1q, genetic testing for HAEDrug 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 drugNo sulfite testingWhen in doubt, biopsy

28Flow diagram for angioedema

29Treatments for urticariaAllergy, Asthma & Clinical Immunology 2011, 7(Suppl 1):S9 doi:10.1186/1710-1492-7-S1-S9

30CyclosporineLow 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 monthsToubi E et al Allergy 1997; 52: 312-6DBPC 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 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

33Case in questionStopped ASA and ACEI, and switched to ARBTreated H.pylori with triple therapy, and UTI Angioedema and hives resolvedShe takes Reactine and Ranitidine only as needed now, and off oral prednisoneNasocorticosteroids, Atrovent nasal spray , nasal washes prn34Key pointsThrough several mechanisms a variety of mediators may lead to urticaria or angioedemaClinically, a causative agent is much more often identified in acute than in chronic urticaria/angioedemaA number of medications are available to control chronic urticaria while awaiting a spontaneous remissionPatients with angioedema without urticaria should be tested for C1 inhibitor deficiencyRecurrent infections, especially with other symptoms (rashes, alopecia, diarrhea) should be worked up for primary immunodeficiency

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