Read Wallach's Interpretation of Diagnostic Tests: Pathways to Arriving at a Clinical Diagnosis for Free Online Page A

thrombocytopenia may develop or be aggravated by splenomegaly (hypersplenism).
   Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) are very elevated.
   Circulating immune complexes and immunoglobulin levels are higher than those found in RA.
   Peripheral blood smear review and bone marrow aspirate or biopsy may be indicated to exclude other causes of neutropenia.
MIXED CONNECTIVE TISSUE DISEASE
   Definition
   Mixed connective tissue disease (MCTD) represents an overlap syndrome with features of systemic lupus erythematosus (SLE), systemic sclerosis, and polymyositis.
   The disease can be serious with development of kidney, cardiovascular, gastrointestinal, and central nervous system manifestations. Pulmonary disease is associated with the highest mortality.
   Who Should Be Suspected?
   Presenting 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.
   MCTD usually develops in the second or third decade of life, and is more common in women than men.
   Laboratory Findings
   Positive ANA, with a high-titer speckled pattern (>1:1,000 and often >1:10,000) using the indirect fluorescent antibody test (IFA).
   Presence 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.
   Anti-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.
   Antiphospholipid 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.
   Elevated ESR and CRP.
   Positive RF and anti-CCP antibodies in approximately 50% of the patients.
   Anemia, 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.
POLYMYALGIA RHEUMATICA
   Definition
   Polymyalgia rheumatica (PMR) is an inflammatory rheumatic disorder characterized by morning stiffness and pain in the muscles of the shoulders, neck, back, hip, and thighs.
   The 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:
   Morning stiffness for more than 45 minutes (2 points)
   Hip pain/ limited range of motion (1 point)
   Absence of rheumatoid factor and/or anti–citrullinated protein antibody (2 points)
   Absence of peripheral joint pain (1 point)
   A 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.
   Who Should Be Suspected?
   The 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.
   PMR develops in nearly