Allergy & Immunology: Autoimmune diseases

Question 1

ATOPIC DERMATITIS

Answer 1

Topical corticosteroids are the first-line therapy for atopic dermatitis. Their mechanism of action includes decreasing tissue production of proinflammatory prostaglandins and leukotrienes through the inhibition of phospholipase A2; they also inhibit transcription of many other proinflammatory mediators. [21294]
Atopic dermatitis presents with dry, erythematous patches or papules that are caused in part by a Th2-skewed immune response. Th2 cytokines (eg, IL-4, IL-13) stimulate IgE production, suppress epidermal barrier component expression, and impair host immune responses against secondary microbial infections. [21258]

Question 2

AZATHIOPRINE

Answer 2

Azathioprine is an immunosuppression drug that inhibits purine nucleotide synthesis and incorporates false purine
nucleotides into DNA and RNA. These effects reduce the proliferation and activity of both B and T lymphocytes. [18704]

Question 3

CELL MEDIATED IMMUNITY

Answer 3

FOXP3 is a transcriptional regulator protein that is required for the development of regulatory T cells; it triggers production of cytokines (eg, IL-10, transforming growth factor-beta) and ligands (eg, cytotoxic T-lymphocyte antigen- 4) that suppress immune activation. FOXP3 mutations result in immune dysregulation marked by excessive immunoglobulin production and the development of autoimmunity. [15331]

Question 4

CORTICOSTEROIDS

Answer 4

Budesonide, like other glucocorticoids, reduces inflammation by binding to a cytosolic receptor, translocating into the nucleus, and inhibiting proinflammatory transcription factors such as nuclear factor-kappa-B (NF-κB). It is especially useful in reducing transmural bowel inflammation in patients with Crohn disease because it has high topical potency and limited systemic adverse effects due to high first-pass metabolism. [18802]
Glucocorticoids have a variety of effects that can be useful in reducing inflammation and limiting end-organ damage in inflammatory diseases (eg, sarcoidosis). These include decreased proinflammatory cytokine (IL-1, interferon-gamma) production, increased anti-inflammatory cytokine (eg, IL-10) production, and impaired migration of leukocytes (eg, neutrophils) to sites of inflammation. [18803]
The acute effects of corticosteroids on the white blood cell count include an increased neutrophil count and decreased lymphocyte, monocyte, basophil, and eosinophil counts. The increase in the neutrophil count results from “demargination” of neutrophils previously attached to the vessel wall. [549]

Question 5

GRANULOMATOSIS WITH POLYANGIITIS

Answer 5

Necrotizing vasculitis of the upper and lower respiratory tract (causing nasal ulcerations, sinusitis, hemoptysis) and rapidly progressive glomerulonephritis—producing a variable degree of renal failure—is characteristic of granulomatosis with polyangiitis (Wegener). This disease is associated with C-ANCAs, which may target neutrophil proteinase 3.

Question 6

IGA VASCULITIS

Answer 6

Henoch-Schönlein purpura, or IgA vasculitis, classically presents with palpable purpura, with or without abdominal pain, arthralgias, and renal involvement. Histopathologic examination of the skin lesions reveals damaged small vessels with fibrinoid necrosis, perivascular neutrophilic inflammation, and nuclear debris (ie, leukocytoclastic vasculitis). Immunofluorescence reveals deposition of IgA and C3.

Question 7

MALABSORPTION

Answer 7

Crohn disease with ileal resection or extensive ileal involvement can cause bile acid malabsorption, which may lead to impaired absorption of fat-soluble vitamins (A, D, E, K). Vitamin K deficiency can result in impaired coagulation with easy bruising, large hematoma formation in deep tissues and joints (eg, hemarthrosis) after minor trauma, and prolonged bleeding after surgery. [12047]

Question 8

ODONTOGENIC INFECTIONS

Answer 8

Sjögren syndrome is characterized by autoimmune inflammation of exocrine glands (eg, salivary, lacrimal,
vaginal). Patients typically have severe dry mouth (xerostomia) due to reduced saliva production, which can lead to an increased rate of dental caries and other oral infections (eg, thrush) because of the loss of protective factors in saliva. Biopsy of the salivary glands shows a lymphocytic infiltrate, often with germinal centers. [15557]

Question 9

SLE

Answer 9

Antinuclear antibodies are found in almost all patients with systemic lupus erythematosus but are also found in many other autoimmune disorders and have low specificity. Anti–double-stranded DNA antibodies and anti-Smith antibodies have lower sensitivity but higher specificity. [761]
Systemic lupus erythematosus is an autoimmune disorder that occurs most commonly in women. Hematologic abnormalities are common; autoantibodies against blood cell antigens (ie, type II hypersensitivity) can cause pancytopenia (ie, anemia, thrombocytopenia, leukopenia). In contrast, lupus nephritis is caused by immune complex deposition (ie, type III hypersensitivity) in the glomer

Question 10

SERUM SICKNESS

Answer 10

Serum sickness is a type III hypersensitivity reaction to nonhuman proteins characterized by vasculitis resulting from tissue deposition of circulating immune complexes. Clinical findings include fever, pruritic skin rash, arthralgias, and low serum C3 and C4 complement levels.