Pain in Sjogren's Syndrome

Motivation: Every time someone comes with painful feet, I ask "Do you have dry mouth or dry eyes?" Patients usually look at me suspiciously.  What does dry eyes have to do with painful feet?  Sjogren's syndrome, of course  - an elusive syndrome of dry eyes, dry mouth, and autoimmune destruction of exocrine glands often with associated peripheral neuropathy.  To avoid those suspicious glances, I wonder what are the characteristics of neuropathy from Sjogren's syndrome.

Paper: Berkowitz, AL and Samuels MA. "The neurology of Sjogren's syndrome and the rheumatology of peripheral neuropathy and myelitis." Pract Neurol (2013); 0: 1-9.

Methods: Review of peripheral nervous system presentations of Sjogren's syndrome and characteristics of serologic testing.  This is part of a broader paper reviewing Sjogren's associated myelitis as well.

Results:
Prevalence: Neuropathy accompanies Sjogren's syndrome in approximately 5-15% of cases.  Neuropathy preceded other symptoms in 37%, occurred concurrently in 16%,and occurred after other symptoms in 37%.

Types of Neuropathy: The most common forms of neuropathy involve the dorsal root ganglia (hence pure sensory loss) in 39% and small unmyelinated fibers (hence painful) in 20%.  Other presentations included trigeminal neuropathy in 16%, multiple mononeuropathies in 12%, multiple cranial neuropathies in 5%, and polyradiculoneuropathies in 4%.

Testing: The classical serum auto-antibodies anti-Ro (SSA) and/or anti-La (SSB) occur in 10-55% of patients with Sjogren's neuropathy.  For dorsal root involvement, the sensitivities of SSA and SSB are 53% and 11%.  For painful small fiber neuropathy, the sensitivities of SSA and SSB are 39% and 17%.  Anti-nuclear antibody (ANA) is positive in 20-67%.  Schirmer's test evaluating tear production (degree of moistening of filter paper in lower eyelid after 5 minutes) is positive in 56-89%.  Lip salivary gland showing lymphocytic infiltration is diagnostic in 37-75% of patients.

Discussion: 
The first depressing conclusion of this paper is that the manifestations of Sjogren's syndrome are protean without good diagnostic tests.  Nonetheless, Sjogren's associated neuropathy is most often sensory in nature (dorsal root gagnlia or just painful neuropathy) without significant motor involvement.  The second point is that serologic testing may be negative in about 50% or even more number of patients.  Similarly, classical symptoms of dry eyes or dry mouth may follow neuropathy and should not be used to exclude Sjogren's syndrome.  In the office, stocking filter paper and learning to perform the Schirmer's test may be more helpful than sending for serologic testing.  

Lipoprotein (a) Value

Motivation: Lipoprotein (a) inspires strong emotions among doctors.  Some like it as a risk factor while others see it as a waste of money.  But, when controlled for conventional lipid markers, is it indicative for additional risk for cardiovascular disease?  For background, lipoprotein (a) is a low density LDL-like particle synthesized by the liver which is found in the intima of arteries and presumably promotes atherosclerosis.

Paper: The Emerging Risk Factors Collaboration. "Lipoprotein (a) Concentration and the Risk of Coronary Heart Disease, Stroke, and Nonvascular Mortality."   JAMA (2009); 302: 412-423.

Methods: Meta-analysis of long-term prospective studies that recorded Lipoprotein (a) (Lp(a)) and vascular morbidity.

Results:
Studies: 36 prospective studies met inclusion criteria.  In the analysis, 126 634 participants were included for 1.3 million person-year of follow-up with 22 076 vascular disease outcomes or death.  Mean age at entry was 57 years with 48% women.  Ethnicity was 47% European and 50% North American.

Lipoprotein (a): At baseline, the overall population Lp (a) was 12.6 mg/dL.  Blacks had 119% (95% CI: 84 to 161) higher Lp(a) concentration compared to whites at baseline.  Women had 12% (CI: 8 to 16) higher Lp (a) than men.

Coronary Heart Disease (CHD): When adjusted for age, sex, systolic blood pressure, smoking, diabetes, and total cholesterol, the relative risk of coronary heart disease for the top third of Lp (a) compared to the bottom third was 1.27 (95% CI: 1.17-1.38).  In the top third of subjects with Lp (a), the rate of CHD was 5.6 (95% CI: 5.4-5.9) per 1000 person years compared to rate of 4.4 (95% CI: 4.2-4.6) per 1000 person years in the bottom third.

Ischemic Stroke: When adjusted for usual risk factors, the relative risk (RR) for ischemic stroke was 1.10 (95% CI: 1.02-1.18) per 3.5 fold higher than usual Lp (a) levels.  The relative risk did not reach significance for unclassified stroke and hemorrhagic stroke.

Non-vascular mortality: Lp (a) levels were not associated with increase in non-vascular mortality.

Discussion: Lipoprotein (a) is very modestly associated with independent risk of coronary heart disease and ischemic stroke.  As stated in the paper, compared to the power of Lp (a), elevated non-HDL cholesterol level is four times more strongly associated with coronary heart disease.  There is no drug that independently targets Lp (a) levels.  Consequently, I do not think that at present, it is worth measuring this modestly predictive marker without clear treatment.  The paper, though, illuminated the variability of Lp (a) across ethnicities (blacks have baseline of 100% greater than whites) and genders.  When interpreting raw values of Lp (a), we have to be careful about using correct gender and ethnicity matched norms, which may not exist in all cases.