ABIM Allergy Immunology Review 2014

1. ABIM Allergy Immunology Review2014 Richard D. deShazo, MD with thanks to the many colleagues from whom I have borrowed material

2. Questions: What are the major diagnostic criteria for asthma? • How can you separate asthma from COPD? • What does a positive methacholine inhalation test mean?

3. Spirometry before and after an inhaled bronchodilator showing reversible airway obstruction

4. Asthma Diagnosis • FEV1 improvement of 12% and 200mL after beta-agonist is evidence for asthma according to ATS • Decreased FEV1/FVC ratio • 20-39yr 85% • 40-59yr 80% • 60-80yr 70% • Methacholine challenge – not diagnostic of asthma • + with 20% decrease FEV1 with <8-16mg/mL • True benefit is in negative predictive value

5. Question: What test should be considered in a young asthmatic female with recurrent episodes of wheezing poorly responsive to bronchodilators?

6. Vocal Cord Dysfunction Is Not Asthma, But May Occur In Asthmatics Flow volume loops showing maximum inspiratory and expiratory flow-volume relationships in a patient with vocal cord dysfunction during asymptomatic (left) and symptomatic (right) periods. Note also the marked adduction of the vocal cords with severe reduction of the glottic aperture during a symptomatic period (right) of airway obstruction.

7. Vocal Cord Dysfunction • Female 2:1 • Athletes • Bronchodilator non responsive • Many (up to 1/3) can have coexist asthma • Difficulty getting breath in

8. 2 Questions: What is the likely diagnosis in a man with persistent cough, shortness of breath, dyspnea, and episodic wheeze that developed after working as a police officer in the 9/11 exposure area in NYC? A 22 year old with recent onset cough and wheeze works in a custom sailboat shop in Biloxi sealing the inside of boats with epoxy resins. What is the most likely low molecular weight chemical causing his symptoms?

9. Reactive Airways Dysfunction Syndrome (RADS): Not Asthma • Treatment – Time + corticosteroids • Occurs after a single inhalation of a caustic irritant in a non-asthmatic • Obstruction on PFT • (+) methalcholine inhalation challenge • Limited PFT-response to beta-agonists • Not “reactive airways disease”

10. Occupational Asthma • Basically, asthma occurring because of exposure at work. • Testing difficult, so sometimes need to do pulmonary evaluation at the workplace. (Start with peak flows at work versus home). • Earlier you diagnose the better, because may lead to permanent asthma even when removed from environment.

11. Risk Factors for Asthma Death • Previous life-threatening asthma such as respiratory arrest • Hospitalization or ED visit for asthma within the last year • Use of 2 or more canisters of rescue inhaler/month • Poor perception of hypoxia or airway obstruction • Psychosocial disturbance

12. Classification of Asthma Severity

13. Asthma Pharmacotherapy • Rescue medicines • Short acting agonists (SABA) • Anticholinergic • Controller medicines • Inhaled corticosteroids (ICS) • Long acting agonists (LABA) • Leukotriene receptor antagonists (LTRA) • Combinations of ICS & LABA • Anti-IgE (omalizamab) • Others

14. Stacking Asthma Drugs

15. What Meds Should You Think About Adding On In Severe Asthma?

16. Things to consider in the out of control asthmatic • Vocal cord dysfunction • GERD • Sinusitis • Churg-Strauss syndrome • ABPA • Compliance/technique

17. How Do You Assess Asthma Control?

18. How Do You Use A Metered Dose Inhaler (MDI)?

19. What Does Every Asthmatic Have to Have?

20. 3 Eosinophilic Lung Diseases • Churg-Strauss Vasculitis • Sinusitis, asthma, eosinophilia, vasculitis • Transient pulmonary infiltrates • Small vessel vasculitis • Neuropathies (mononeuritis multiplex) • MPO- ab/P-ANCA test (+) in about 50% • RX: steroids (cyclophosphamide/azathioprine in severe) • ? relationship to LTRA

21. Allergic Bronchopulmonary Mycosis (ABPM) • Includes allergic bronchopulmonaryaspergillosis (ABPA) and other allergic mycoses • Criteria • Asthma • Fleeting pulmonary infiltrates • High total IgE (>1000 ng/mL or 417 kU/L) • Positive immediate skin test (IgE) to fungus (A. fumigatus, etc.) or Positive RAST test • Elevated serum specific IgE to fungus (A. fumigatus, etc.) • CT with central bronchiectasis reflects chronic disease

22. Treatment of ABPM • Oral corticosteroids • Follow total serum IgE and CXR • No long term studies on Itraconazole as steroid sparing agent

23. Hypereosinophilic Syndrome • No increase asthma but may have allergic – like dermatitis • Paramalignant syndrome • Peripheral blood eos count >1500 µL for at least 6 months • Absence of any other known cause of eosinophilia • Presumptive signs/symptoms of organ invasion by eosinophils • 9:1 male:female • Systemic disease • Cardiac disease (thrombosis, fibrosis, necrosis) is the most common cause of death • FIP1L1/PDGFA fusion-gene present in some patients

24. Organs Involved in Hypereosinophlic Syndrome • Heart • Skin, Lungs, GI tract, Nervous System • Vascular thrombosis is a feared complication • Treatment • Steroids • Hydroxyurea • Interferon α • Gleevac (imatinib) - for FIP1L1-PDGFRα gene rearrangement

25. Question: A 50 year old woman with asthma and atopic dermatitis has her 3rd episode of food impaction. What findings should be sought from endoscopy to confirm the diagnosis?

26. Eosinophilic Gastroenteritis • Atopic individuals • Usually in upper tract • Food impaction in esophagus • Mucous furrowing and white specks on endoscopy • More than 12 eosinophils/HPF on biopsy • Food allergy in some • Treated with non-absorbable steroids

27. Question: A 50 year old bird breeder has persistent shortness of breath, cough, and dyspnea. What should be done?

28. Hypersensitivity Pneumonitis • Fever, chills, malaise, cough, dyspnea • Acute, subacute, chronic • A systemic illness • Also known as “extrinsic allergic alveolitis” • Non allergic, not IgE mediated, no eosinophilia, no asthma except pigeon breeder’s (bird fancier’s) lung • T-cell mediated • CXR/CT scan abnormal: ground glass/diffuse alveolar pattern • PFT – restriction not obstruction except for pigeon breeders • Chronic  pulmonary fibrosis

29. Approach to Allergic Rhinitis • Characterize chronicity looking for seasonal variation. • Ask for family history, indoor triggers and nasal itching. • Swollen nasal mucosa usually more blue that red. • Treat • If there is treatment failure, do allergy skin tests or RASTs to determine specific allergen and consider allergy shots. • Allergy shots are very effective for allergic rhinitis and insect anaphylaxis.

30. Allergic Rhinitis • Nasal steroids – first line treatment • Antihistamines and leukotriene receptor antagonists – second line (about equal efficacy as second line agents) • To prevent symptoms on planned exposures, chromolyn or antihistamines work best • Allergen immunotherapy by subcutaneous or sublingual techniques

31. Mimics of Allergic Rhinitis • Vasomotor rhinitis • Rhinitis medicamentosa • Nasal manifestations of systemic disease: • Diabetes mellitus – mucor mycosis (nasal eschar; black crust) • Wegener’s granulomatosis (saddle nose) • Midline granuloma (saddle nose) • Relapsing polychondritis (saddle nose) • Sarcoidosis (bloody crusts) • Cystic fibrosis (nasal polyps) • CSF leak – check beta 2 transferrin (very specific)

32. Rhinosinusitis Syndromes withNasal Polyposis • Immunodeficiency • Cystic fibrosis • Aspirin – sensitive respiratory disease • Allergic fungal sinusitis • Anosmia is a big tip off for polyps

33. Acute & Chronic Sinusitis Ethmoid cell

34. Question: A 30 year old nurse has a severe chronic dry and cracking dermatitis of both hands. What should you do first?

35. Irritant vs. Allergic Contact Dermatitis Patch testing can detect both irritant and allergic contact dermatitis, if the tests are read at appropriate times. Consider a patch test a TB skin test. Positive results are erythema and induration maximum at 24-48 hours.

36. MKSAP Most Frequently Positive Patch -Test Results in Allergic Contact Dermatitis

37. Question: A 16 year old male with asthma has a chronic pruritic dermatitis in the flexural areas of his elbows and knees. What treatment would be best for this problem?

38. Atopic Dermatitis (Eczema) (1) Atopic dermatitis with involvement of a flexural surface. The frequently involved anticubital and popliteal fossae.

39. Atopic Dermatitis (2) • Increased susceptibility to • Staph aureus, HSV (eczema herpeticum), vaccinia • Differential diagnosis • Allergic contact dermatitis • Irritant contact dermatitis (gloves) • Cutaneous T – cell lymphoma An adult presenting with eczematous dermatitis with an erythrodermatous appearance by skin biopsy with genetic studies • Atopic dermatitis is associated with abnormalities in the filaggrin gene which encodes for filaggrin protein important in statiumcorneammoisturization

40. Treatment of Atopic Dermatitis • Skin hydration/moisturization (Aquaphor) • Medium strength topical corticosteroids and combinations (equal parts 0.1% triamcinolone and Aquaphor) • Oral antibiotics (Staph) • Antihistamines (control itch) • Topical calcineurin inhibitors (protopic/ elidel)

41. MKSAP Clinical Clues to the Diagnosis of Selected Causes of Erythroderma

42. Urticaria • Classification of Urticaria • Acute urticaria (<6 weeks) • Chronic urticaria (>6 weeks) • Physical urticaria (pressure, cold, vibratory, etc.) • Urticarial vasculitis • Contact urticaria (touching a cat) • Urticaria and angioedema as components of anaphylaxis

43. Classification of Physical Urticarias

44. Palpable purpura is a clinical sign of a small vessel (leukocytoclastic) vasculitis which may present as chronic urticaria.

45. Question: A 68 year old female with chronic mylogenous leukemia presents with non itchy swelling of the lips and throat. What diagnostic tests would be most useful to diagnose acquired angioedema?

46. Differential Diagnosis: Cutaneous and/or Laryngeal Swelling • Allergic reactions and anaphylaxis • Idiopathic angioedema • Drug induced angioedema • Allergic contact dermatitis • Autoimmune conditions • Thyroid disorders • Superior vena cava syndrome and tumors • Cheilitisgranulomatosa (Miescher’scheilitis) and Melkersson-Rosenthal syndrome • Trichinosis • Low C-4 levels

47. Hereditary Angioedema • Autosomal Dominant • Hiveless, itchless edema • Hereditary angioedema form more likely to have symptoms precipitated by trauma - dental visit, surgery, auto accident, menses, puberty • Visceral attacks may present as an acute abdomen with normal findings at surgery

48. Symptoms: Painless, itchlessangioedma with/without family history • Diagnosis of HAE5 • HAE 1 - low C41, 2 low C1 INH, low C1INH-F • HAE2 - low C41, 2normal C1 INH, low C1INH-F • Acquired – low C41, 3low C1 INH, low C1INH-F, low Clq • HAE3 – normal C4 4 normal C1 INH, normal C1INH-F, normal C1f level • Always low during attacks • SERPING1 gene abnormalities • Antibodies to C1INH • Abnormalities in Factor XII genes • Family members should be screened in all types

49. Acquired Angioedema • Associated with lymphoproliferative disorders • Have low C1q levels • Mechanism unclear • Low C1 of levels appear to reflect autoactivation • Anti – C1 esterase inhibitor antibodies have been described as well

50. Tests for Hereditary/Acquired Angioedema • C4 – is a great screening test, but is normal in HAE Type 3 • Test for C1 esterase inhibitor level and function to discriminate between two hereditary types • Test C1q level for the acquired form • Genetic testing for HAE Type 3