2 Autoimmune Diseases

Genetic susceptibility, mostly due to linkage to particular HLA molecules

Square bulletEnvironmental triggers (e.g., drugs, chemicals)

Square bulletInfectious agents (e.g., Mycoplasma pneumoniae, HIV)

Square bulletLoss of regulatory T cells

Square bulletDefects in cytokine production


Organ-specific autoimmune diseases involve a particular organ or tissue of the body in which the target autoantigen is found. Examples of these autoimmune diseases and their target organs:

Square bulletAdrenal glands (e.g., autoimmune adrenal insufficiency). See Chapter 6, Endocrine Diseases

Square bulletBile ducts (e.g., primary biliary cirrhosis). See Chapter 5, Digestive Diseases

Square bulletBlood cells: RBC (e.g., autoimmune hemolytic anemia), WBC (e.g., autoimmune neutropenia), platelets (e.g., immune thrombocytopenic purpura). See Chapter 9, Hematologic Disorders

Square bulletBlood vessels (e.g., autoimmune vasculitis). Discussed in this Chapter and in Chapter 3, Cardiovascular Disorders

Square bulletGastrointestinal tract (e.g., celiac disease, Crohn disease, ulcerative colitis). See Chapter 5, Digestive Diseases

Square bulletKidney (e.g., anti–glomerular basement membrane antibody disease). See Chapter 12, Renal Disorders

Square bulletLiver (e.g., autoimmune hepatitis). See Chapter 5, Digestive Diseases

Square bulletNervous system (e.g., myasthenia gravis [a disorder of the neuromuscular junction], multiple sclerosis, Guillain-Barré Syndrome, autoimmune autonomic failure). See Chapter 4, Central Nervous System Disorders

Square bulletPancreas: type 1 diabetes mellitus (see Chapter 6, Endocrine Diseases), autoimmune pancreatitis (see Chapter 5, Digestive Diseases)

Square bulletThyroid gland (e.g., Hashimoto thyroiditis, Graves disease). See Chapter 6, Endocrine Diseases




Square bulletFelty syndrome is characterized by the triad of long-standing, aggressive rheumatoid arthritis (RA), neutropenia, and splenomegaly.

Square bulletIt develops in a minority of patients with RA (<1%).

imageWho Should Be Suspected?

Square bulletPatients typically present with general malaise, fatigue, loss of appetite, and unintentional weight loss. Some patients have recurrent infections, such as respiratory or skin infections, attributed to the neutropenia.

Square bulletThe syndrome is more common in women >30 years of age and in patients with a family history of RA.

imageLaboratory Findings

Square bulletNeutropenia (<2,000 granulocytes/μL) is required for diagnosis. WBC count is usually <2,500/μL.

Square bulletElevated levels of rheumatoid factor (RF) and anti–cyclic citrullinated peptide (anti-CCP) antibodies (high titers).

Square bulletAntinuclear antibodies (ANAs), antihistone antibodies, and antineutrophil cytoplasmic antibodies (ANCAs) are found in more than two thirds of patients.

Square bulletAnti-glucose-6-phosphate isomerase antibody titer is elevated in the majority of patients.

Square bulletAnemia and thrombocytopenia may develop or be aggravated by splenomegaly (hypersplenism).

Square bulletErythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) are very elevated.

Square bulletCirculating immune complexes and immunoglobulin levels are higher than those found in RA.

Square bulletPeripheral blood smear review and bone marrow aspirate or biopsy may be indicated to exclude other causes of neutropenia.



Square bulletMixed connective tissue disease (MCTD) represents an overlap syndrome with features of systemic lupus erythematosus (SLE), systemic sclerosis, and polymyositis.

Square bulletThe disease can be serious with development of kidney, cardiovascular, gastrointestinal, and central nervous system manifestations. Pulmonary disease is associated with the highest mortality.

imageWho Should Be Suspected?

Square bulletPresenting symptoms are often nonspecific, such as fatigue, myalgia, arthralgia, and low-grade fever. In the early stages of disease, 90% of MCTD patients have Raynaud phenomenon, arthralgia, swollen hands, fingers with “sausage-like” appearance, and muscle weakness. Other common symptoms that may develop gradually include swollen joints, esophageal dysfunction, sclerodactyly, and calcinosis.

Square bulletMCTD usually develops in the second or third decade of life, and is more common in women than men.

imageLaboratory Findings

Square bulletPositive ANA, with a high-titer speckled pattern (>1:1,000 and often >1:10,000) using the indirect fluorescent antibody test (IFA).

Square bulletPresence of high titers of anti-U1 ribonucleoprotein (anti-RNP) antibodies, especially antibodies to the 68 kDa protein, is highly suggestive of an MCTD diagnosis and separates it as an independent disease.

Square bulletAnti-SSA/Ro, anti-single-stranded DNA (ssDNA), anti-Smith (Sm), and anti-double-stranded DNA (dsDNA) antibodies have also been detected, but they are not specific for MCTD.

Square bulletAntiphospholipid antibodies have been reported in patients with MCTD, with a lower frequency than that found in SLE. Anticardiolipin antibodies (ACAs) are present in approximately 15% of MCTD patients.

Square bulletElevated ESR and CRP.

Square bulletPositive RF and anti-CCP antibodies in approximately 50% of the patients.

Square bulletAnemia, leukopenia, and hypergammaglobulinemia may present.

Suggested Reading

Ortega-Hernandez OD, Shoenfeld Y. Mixed connective tissue disease: an overview of clinical manifestations, diagnosis and treatment. Best Pract Res Clin Rheumatol. 2012;26(1):61–72.



Square bulletPolymyalgia rheumatica (PMR) is an inflammatory rheumatic disorder characterized by morning stiffness and pain in the muscles of the shoulders, neck, back, hip, and thighs.

Square bulletThe 2012 European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) classification criteria for PMR use a scoring algorithm that applies to patients >50 years of age, presenting with new bilateral shoulder pain (not better explained by an alternative diagnosis) and elevated CRP/ESR. The elements of this algorithm include the following:

imageMorning stiffness for more than 45 minutes (2 points)

imageHip pain/ limited range of motion (1 point)

imageAbsence of rheumatoid factor and/or anti–citrullinated protein antibody (2 points)

imageAbsence of peripheral joint pain (1 point)

Square bulletA score of 4 or more has 68% sensitivity and 78% specificity for distinguishing PMR patients. Ultrasound findings of bilateral shoulder abnormalities or abnormalities in one shoulder and hip were found to significantly improve both sensitivity and specificity of the clinical criteria.

imageWho Should Be Suspected?

Square bulletThe disease is almost exclusively found in individuals >50 years of age. Patients typically present with general malaise, fatigue, as well as aches and morning stiffness in the shoulder, hip girdles, neck, lower back, and knees. Loss of appetite, unintentional weight loss, and depression are also common findings.

Square bulletPMR develops in nearly 50% of patients with giant cell arteritis (GCA), and 15–30% of patients with PMR eventually develop GCA.

imageLaboratory Findings

Laboratory finding are nonspecific.

Square bulletESR is markedly elevated (>40 mm/hour, but values >100 may be seen). However, some patients with mild disease may have only slight elevations of ESR.

Square bulletCRP is elevated and considered a more sensitive marker than ESR.

Square bulletSerologic tests such as RF, ANA, and anti-CCP antibodies are typically negative.

Suggested Reading

Dasgupta B, Cimmino MA, et al. 2012 provisional classification criteria for polymyalgia rheumatica: a European League Against Rheumatism/American College of Rheumatology collaborative initiative. Ann Rheum Dis. 2012;71(4):484–492.



Square bulletPolymyositis (PM), dermatomyositis (DM), and inclusion body myositis (IBM) are related inflammatory myopathies that share common features, including muscle weakness and inflammatory infiltrates on a muscle biopsy.

Square bulletPM and DM are characterized by a subacute onset of symmetric proximal muscle weakness, common involvement of other organ systems such as lung and skin, a strong association with autoantibodies, and responsiveness to immunosuppression. Both are widely accepted as having an autoimmune basis. Cutaneous involvement is the primary clinical feature distinguishing patients with DM from those with PM.

Square bulletIn contrast to PM and DM, patients with IBM typically have slowly progressive weakness in both proximal and distal muscles, rarely have other extra-muscular involvement or autoantibodies, and most often do not respond to immunosuppressive therapies. A muscle biopsy showing the presence of typical inclusion bodies is diagnostic for IBM.

imageWho Should Be Suspected?

Square bulletPatients with PM and DM typically present with progressive proximal muscle weakness and evidence of muscle inflammation. They may also have constitutional symptoms and evidence of involvement of other organs (e.g., interstitial pulmonary disease, polyarthritis). DM patients can be differentiated by having specific cutaneous signs such as Gottron papules or heliotrope eruption.

Square bulletPatients with IBM generally have a more insidious onset compared to PM and DM, and more prominent distal muscle weakness.

Square bulletPM and DM can occur at any age, with peak incidence between the ages of 40 and 50, whereas IBM mainly affects individuals >50 years of age.

imageLaboratory Findings

Diagnosis of the three conditions is based on clinical manifestations, serum muscle enzymes, autoantibodies, EMG findings, and muscle biopsy. The latter is the definitive test for establishing the diagnosis of IBM, and in PM or DM patients presenting with atypical clinical or laboratory findings.

Square bulletMuscle enzymes:

imageLevels of the muscle enzyme creatine kinase (CK) are greatly elevated in PM and DM patients (typically >10 folds the upper limit of normal but may be >50 folds), and to a lesser extent in patients with IBM.

imageOther muscle enzymes including lactate dehydrogenase (LDH), aldolase, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) are also elevated. Similar to CK, elevations are less profound in IBM than in PM or DM.

Square bulletANA test is positive in up to 80% of patients with DM or PM.

Square bulletMyositis-specific antibodies are positive in 30% of patients with PM or DM. The most common antibodies are those against histidyl-tRNA synthetase (anti-Jo-1), and titers of these antibodies have been found to correlate with disease activity. Other myositis-specific antibodies include anti-Mi-2 and anti–signal recognition particle (anti-SRP) antibodies. Presence of other connective disease conditions associated with myositis is suggested when another type of autoantibodies is positive (e.g., anti-SSA/Ro, anti-SSB/La, anti-Sm, or anti-RNP).

Square bulletESR is normal or mildly increased.

Square bulletMyoglobin is elevated in the serum and urine.

Suggested Reading

Mammen AL. Dermatomyositis and polymyositis: clinical presentation, autoantibodies, and pathogenesis. Ann N Y Acad Sci. 2010;1184:134–153.



Square bulletPsoriatic arthritis (PsA) is a type of arthritic inflammation that occurs in approximately 15% of patients with psoriasis. It can affect any joint in the body causing pain, swelling, and stiffness. CD8+ T cells and T-cell-derived cytokines play a central role in the pathogenesis of PsA.

Square bulletThe Classification Criteria for Psoriatic Arthritis (CASPAR) require the presence of joint, spine, or entheseal inflammatory disease plus a minimum score of 3 points from the following five categories (98.7% specificity and 91.4% sensitivity):

imageCurrent psoriasis (2 points); personal or family history of psoriasis (1 point)

imageTypical psoriatic nail dystrophy (1 point)

imageNegative rheumatoid factor (1 point)

imageCurrent dactylitis or history of dactylitis (1 point)

imageHand or foot plain radiography demonstrating juxta-articular new bone formation (1 point)

imageWho Should Be Suspected?

Square bulletMost patients who develop PsA have skin symptoms of psoriasis first (erythematous papule and plaques with a silver scale), followed later by arthritis symptoms characterized by pain, tenderness, and stiffness in the joints and back.

Square bulletSeveral HLA types have been identified to be associated with PsA, suggesting a genetic predisposition. This is also indicated by the presence of a family history of psoriasis and psoriatic arthritis in up to 40% of patients.

imageLaboratory Findings

Laboratory finding are not specific.

Square bulletESR and CRP are elevated in approximately 50% of cases; levels correlate with the number of involved joints.

Square bulletRF is negative.

Square bulletAnemia of inflammation, hypergammaglobulinemia with increased IgA levels, and hypoalbuminemia have been reported in some cases.

Square bulletHyperuricemia, related to either increased skin cell turnover or metabolic defect, is found in nearly 20% of patients.

Square bulletHLA testing can be helpful: HLA Cw6 is the most important allele for susceptibility to early-onset psoriasis; HLA-B17 may be associated with a more severe phenotype.

Suggested Reading

Cantini F, Niccoli L, Nannini C, et al. Psoriatic arthritis: a systematic review. Int J Rheum Dis. 2010;13(4):300–317.



Square bulletReactive arthritis, formerly known as Reiter syndrome, is an autoimmune spondylarthritis that develops 1–4 weeks after an infection with a pathogen elsewhere in the body. Most often, causing pathogens are urogenital (e.g., Chlamydia) or enteric (e.g., Campylobacter, Salmonella, Shigella, or Yersinia).

imageWho Should Be Suspected?

Square bulletA likely patient is a young adult (20– 40 years of age) who develops postinfectious asymmetric oligoarthritis (affecting most often the knees, ankles, and heels), enthesitis, dactylitis, and lower back pain. In addition, patients may have extra-articular signs including urinary (urethritis, balanitis, dysuria, prostatitis in men, cervicitis, salpingitis or vulvovaginitis in women), ocular (conjunctivitis or anterior uveitis), and/or constitutional (malaise, fever, weight loss) symptoms.

imageLaboratory Findings

Diagnosis is primarily clinical.

Square bulletCulture and serology tests are helpful in identifying the infectious etiology of the disease in only a fraction of cases since pathogens may no longer be retrievable by the time arthritis develops. Nevertheless, a trial to identify the following pathogens by stool or urine cultures, or in some cases by serology, should be attempted:

imageChlamydia, especially Chlamydia trachomatis and Chlamydia pneumoniae. PCR for urinary Chlamydia DNA has high sensitivity.

imageYersinia enterocolitica and Yersinia pseudotuberculosis.

imageSalmonella of various serovars.

imageShigella, especially Shigella flexneri and Shigella dysenteriae.

imageCampylobacter, especially Campylobacter jejuni.

imageClostridium difficile.

imagePossibly other organisms (e.g., HIV, Escherichia coli, Mycoplasma genitalium).

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Nov 3, 2016 | Posted by in GENERAL & FAMILY MEDICINE | Comments Off on 2 Autoimmune Diseases

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