Friday, 18 Oct 2019

You are here

ANA Negative Lupus Nephritis - Does it Exist?

A recent report from the Mayo Clinic describes a 49 year-old patient with lupus nephritis who presented with new-onset hypertension, edema, arthritis, serositis and leukocytoclastic vasculitis, and who later developed glomerulonephritis and nephrotic syndrome.

Labs revealed she was ANA and dsDNA negative, but had evidence of mixed cryoglobulinemia and elevated perinuclear anti-neutrophil cytoplasmic (p-ANCA) and myeloperoxidase (MPO) antibodies. Alll other SLE-related serologies were negative. Kidney biopsy showed diffuse proliferative global glomerulonephritis with a full-house nephropathy pattern on immunofluorescence and electrom microscopy evidence to affirm a type IV glomerulonephritis.

She was treated for LN with prompt renal response to immunosuppression. Cryoglobulins, p-ANCA and MPO titers normalized and the negative SLE serologies remained negative.

Historically, "ANA negative" lupus was a phenomenon seen when rat or mouse cellular substrates were used to detect ANA by indirect immunofluorescence. The problem was that such cell types were devoid of SSA antigens and many patients who were SSA+, but ANA negative, met criteria for lupus.  

This scenario has been rectified by newer technologies and more sensitive assays that no longer miss cases of SSA+ lupus. Yet in the decades since, there has been discussion of "ANA negative" lupus.  I have contended that most of these patients were erroneously diagnosed as lupus, and hence the ANA wouldn't have mattered. I also concede there have been rare cases of ANA negative patients who nonetheless met criteria for lupus but had other autoantibodies (e.g., cardiolipin, dsDNA, SSA antibodies) to affirm the diagnosis. Some of these developed over time. Nonetheless, this is an exceedingly rare phenomenon and this case report gives us another example of how ANA negative lupus can present.

The author also did an extensive literature review to identify 9 articles and 55 cases of suspected ANA-negative or seronegative LN. They examined two groups: (1) LN with negative serology at both presentation and last follow-up ;and (2) LN who were seronegative at presentation but who later developed positive serologies. Other than group one include 40% who had a pediatric onset, little can be gleaned from the subsets and the outcomes they present tabular information 

Hence, ANA negative lupus is rare - very rare. Nonetheless, if lupus or LN is suspected, a lack of SLE antibodies mandates biopsy evidence to confirm the diagnosis and subsequent treatment. 

The author has no conflicts of interest to disclose related to this subject

Rheumatologists' Comments

I would argue that this patient has hypocomplementemia urticarial vasculitis syndrome associated with anti-C1q antibodies. All the clinical manifestations including arthritis, LCV, pericarditis, hive-like lesions, and GN with full-house pattern have been described in this syndrome (J Clin Aesthet Derm 5: 36-46, 2012). I don't see in their article that they tested for the anti-C1q antibody but this should be done. The importance of making that diagnosis is many of these patients develop COPD not related to smoking and dapsone can be a useful preventative therapy.
Fabulous suggestion! Of course the requisite test is not in evidence and the rash they described was a nonpruritic raised red rash - who knows if they missed possible urticaria. Would you be surprised by the presence of a pANCA and MPO antibody in such a patient? Lets hope the authors are reading RheumNow! Thanks Sterling!

More Like This

Protective Effects of ASA and Vasodilators in Systemic Sclerosis

A large cohort study suggests that the use of vasodilators and aspirin (ASA) in systemic sclerosis (SSc) may yield favorable  cardiovascular outcomes.

Myositis Patients at High Risk of Opportunistic Infections

Among patients with systemic rheumatic diseases, the highest incidence of opportunistic infections was seen in those with polymyositis/dermatomyositis (PM/DM), Taiwanese researchers found.

Warfarin Superior to Xarelto in Antiphospholipid Syndrome

A 3 year, multicenter, European, study shows that rivaroxaban was inferior to warfarin in preventing thrombosis in patients with antiphospholipid syndrome (APS) according to the Annals of Internal Medicine. Thus despite the inconvenience of warfarin, it remains the best option for patients with APS.

Declining Trends in Antineutrophil Cytoplasmic Autoantibody–Associated Vasculitis Mortality in the USA

Annals of Internal Medicine reports that age-adjusted mortality rates for antineutrophil cytoplasmic autoantibody–associated vasculitides (AAV) have improved over time - with a decline of nearly 2 percent per year in the United States from 1999 to 2017. Nevertheless, long-term outcomes continue to lag behind mortality rates of the general population.

Serum Interferon Predicts Lupus Flares

Elevated serum levels of interferon-α among patients whose systemic lupus erythematosus (SLE) was in remission helped predict future disease flares, European researchers found.

Among 254 SLE patients who were in remission, 26% had abnormally high serum levels of interferon-α at baseline, according to Alexis Mathian, MD, of Pitié-Salpêtrière Hospital in Paris, and colleagues.