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Patients with Sjogren's syndrome showed significant impairments in olfactory function, Chinese researchers reported.

These patients were more often found to have anosmia (13.5% vs 0%) and hyposmia (19.2% vs 11.5%) compared with healthy matched controls (χ²=10.526, P<0.01), according to Huayong Zhang, MD, and colleagues from the Affiliated Hospital of Nanjing University Medical School in Jiangsu.

In addition, the olfactory impairments correlated with disease activity and symptoms such as dryness and fatigue, they reported online in .

Sjogren's syndrome is characterized by lymphocytic infiltration of the salivary and lachrimal glands, and of the submucosal glands elsewhere such as the stomach, nose, and vagina. Some, though not all, previous studies have suggested that the sense of smell is impaired in Sjogren's syndrome, as well as other autoimmune diseases such as systemic lupus erythematosus and rheumatoid arthritis.

However, olfactory function has not been systematically evaluated in the context of disease activity, so Zhang's group enrolled 52 patients with documented primary Sjogren's syndrome and the same number of age- and sex-matched controls, obtaining pertinent information about demographics, medical history including surgeries and organ involvement, comorbidities, and treatments.

Patients completed the European League Against Rheumatism (EULAR) Sjogren's Syndrome Patient Reported Index (ESSPRI) for pain, fatigue, and dryness, and physicians completed the EULAR Sjogren's Syndrome Disease Activity Index (ESSDAI).

Olfactory function was assessed both subjectively and objectively, with patient-reported ratings on a 10-point scale; zero represented complete loss of smell perception and 10 was excellent acuity. Objective assessment was done with a computerized evaluation that tested for odor threshold, odor identification, and odor memory. On the olfactory threshold test, scores of 1 to 3 were considered anosmia, 4 to 7 were hyposmia, and 8 to 10 were normosmia.

Of the 52 included patients, 49 were women, and mean age was 45. Mean disease duration was 4.5 years.

Erythrocyte sedimentation rate averaged 34.38 mm/h, and mean C-reactive protein level was 11.95 mg/L. Antinuclear antibodies were positive in 83%, anti-SSA antibodies in 78.8%, and anti-SSB antibodies in 28.8%.

Corticosteroids were being used by 76.9%, hydroxychloroquine by 61.5%, and cyclosporin by 23%.

On the objective olfactory function tests, significantly lower scores were observed for patients versus controls:

• Olfactory threshold test, 8.89 versus 10.97 (P=0.001)
• Odor identification test, 19.13 versus 23.84 (P=0.001)
• Odor memory test, 12.88 versus 15.67 (P=0.001)
• Total (threshold + identification + memory), 40.91 versus 50.49 (P=0.001)

On patient-reported subjective assessment, patients again scored lower than controls (6.09 versus 8.25, P<0.01).

On a multivariate analysis, ESSDAI scores were associated with lower scores on the olfactory threshold test (β = -0.266, P=0.046).

Symptoms including dryness, fatigue, and limb pain were also associated with worse scores on threshold, memory, and total scores. Moreover, significant negative associations were observed for ESSPRI scores and the threshold test (r = -0.485), odor identification (r = -0.628), odor memory (r = -0.706) and total scores (r = -0.779; P for all <0.001).

Additional associations were seen between olfactory function and hypocomplementemia, antinuclear antibody positivity, and anti-SSA antibody positivity.

For treatments, a nonsignificant association was seen for patients using glucocorticoids, but no associations were seen for other treatments. The slight association with steroid use may reflect higher disease activity, Zhang and colleagues suggested.

"These data collectively highlight the reduction of olfactory function in primary Sjogren's syndrome patients, correlate with disease activity, and could have useful value in the diagnosis of primary Sjogren's syndrome," they wrote.

Olfactory function and smell identification involve not only activation of olfactory receptor cells, but also higher central nervous system and cognitive skills, they explained.

Nasal function can be impaired by lymphocytic infiltration, resulting in dryness of the nasal tissue, but also by inflammation of the airways. Several pro-inflammatory cytokines are upregulated in Sjogren's syndrome, including interleukins 1β and 6, tumor necrosis factor-α, and interferon-γ, which can interfere with olfactory neurogenesis. "The reduced central nervous olfactory function might be explained by the active systemic inflammation and neuroinflammation in the central nervous system," the authors wrote.

"Although the exact mechanism of olfactory impairment has yet to be elucidated, the possibility of an immune/inflammation-mediated mechanism is intriguing," they concluded.

A limitation to the study was its relatively small sample size, they said.

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