An ANA report has three parts: (1) a positive or negative result; (2) if positive, what the titer is; and (3) the pattern of fluorescence.


ANA patterns. Titers and patterns can vary between laboratory testing sites, most likely because of variation in the methodology used. The commonly recognized patterns are:



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Homogeneous — indicates uniform nuclear fluorescence due to antibody directed against nucleoprotein. 


Peripheral — fluorescence at the edges of the nucleus in a shaggy appearance. Anti-DNA antibodies cause this pattern. 


Speckled — results from antibody directed against different nuclear antigens.


Nucleolar — results from antibody directed against a specific RNA configuration of the nucleolus or antibody specific for proteins necessary for maturation of nucleolar RNA. Nucleolar ANA is seen in patients with systemic sclerosis.


The homogeneous pattern is commonly observed in the general population, and low-positive titers are rarely meaningful. Be aware that a number of significant conditions cause a positive ANA result, such as drug-induced lupus; irritable bowel disease; malignancy; advancing age; viral infections, especially hepatitis C; and other rheumatologic autoimmune diseases.

The clinician should have a high index of suspicion before ordering ANA testing, or he or she will be left to worry about a laboratory result. Too often, the busy clinician who is presented with an array of vague symptoms — from fatigue to low-grade fever to various arthralgias — orders laboratory studies that include an ANA determination. When the result is positive, an unfortunate chain of events may be set off.

Many patients are told that they might have lupus and they are referred to rheumatology. Patients pass their time reading about SLE on the Internet, so that by the time they are seen in rheumatology, the cart is far ahead of the horse, and their anxiety level is high. Requesting a consult with a specialist for a laboratory test is not an appropriate referral, and yet it happens every day. This practice wastes time and money and leads to patient anxiety.

Only 1% of ANA results will be true positives for SLE, and the patient’s clinical picture must fit the diagnosis as well. A rheumatologist is usually needed to make a firm diagnosis of SLE, but many referrals to rule out lupus could be avoided. 


The need for such diagnostic procedures as skin, nerve, or kidney biopsy will often require other subspecialists. A rheumatologist is best qualified to manage cases of authentic lupus. There are many regional autoimmune centers in academic medical centers with large lupus cohorts and multispecialty expertise.


Clinical features and types of lupus


While there are classification criteria for SLE (Table 2), the essential features when considering the diagnosis are: 


  • Age: onset after puberty

  • Population affected: most common in black and Hispanic women in their 20s and 30s 

  • Core features: photosensitive rashes, polyarthritis (not mere arthralgias) of the hands, and nephritis often noticed first

  • Core labs: persistent or large amount of protein in the urine

  • Autoantibody formation quantified by a significantly positive ANA determination (generally felt to be >1:640)


 

The populations in which the preponderance of this disease burden will be found are young black and Hispanic women. Native American women are a third group in which the disease expresses uniquely. Men also develop lupus; it is especially severe in black and Hispanic men. Caucasians are also affected. Older persons can develop SLE as well, but they are outliers on the general epidemiologic curve. 


Although there is a strong familial aggregation, most cases are sporadic. SLE may occur with such other autoimmune conditions as thyroiditis, hemolytic anemia, and idiopathic thrombocytopenia purpura.


Special-case lupus 


Discoid lupus (Figure 1) is a chronic rash typically found on the face and scalp that has characteristic skin findings and is generally ANA-negative. Fewer than 5% of cases progress to SLE.


Subacute cutaneous lupus erythematosus (SCLE) (Figure 2) is often mistaken for a severe fungal rash because it is scaly. Fifty percent of SCLE patients will test positive for ANA, and 50% of patients with SCLE will have SLE. 


Drug-induced lupus is a reactive form of the diseease that develops in response to specific drugs. The presentation consists primarily of arthritis and serositis, such as pleuritis or pericarditis. Patients test positive for ANAs. The condition resolves with cessation of the culprit drug (See “Drugs associated with lupus,” below).