Aysegul Kucukali Turkyilmaz

Investigation of tear osmolarity in early rheumatoid arthritis: relation to disease activity

OBJECTIVE To investigate the frequency of dry eye (DE) by measuring tear osmolarity (TO) with the recently introduced TearLab system (TearLab Corp, San Diego, Calif.) in patients with early rheumatoid arthritis (ERA) and the relationship between the severity of DE and ERA disease activity. DESIGN Prospective study PARTICIPANTS Sixty-four eyes of 64 newly diagnosed and untreated patients with ERA were enrolled in this study. METHODS TO measurements, tear break-up time (TBUT), and Schirmer tests were performed. ERA disease activity was evaluated according to the disease activity score 28 (DAS28). The patients were divided into 3 groups according to DAS28 scores as follows: mild (DAS28 ≤ 3.2), moderate (3.2 < DAS28 ≤ 5.1), and severe (DAS28 > 5.1). RESULTS DE was identified in 46 (71.8%) patients with ERA according to the TO values. There were significant differences among these groups concerning TO (p = 0.001) and TBUT (p = 0.005) scores, whereas there was no significant difference between these groups regarding Schirmer scores (p = 0.200). In addition, DAS28 values were positively correlated with TO values (r = 0.710, p < 0.001), negatively correlated with Schirmer scores, (r = -0.251, p = 0.045), and negatively correlated with TBUT scores (r = -0.335, p = 0.007) among all patients. CONCLUSIONS Our study demonstrated a relationship between the ERA disease activity and severity of DE by using TO measurements with the TearLab system. Therefore, TO measurement could be added to other classical DE tests for diagnosing DE and for assessing the degree of disease activity of ERA.

The effects of whirlpool bath and neuromuscular electrical stimulation on complex regional pain syndrome.

[Purpose] The aim of the present study was to investigate and compare the effects of whirlpool bath and neuromuscular electrical stimulation on complex regional pain syndrome. [Subjects and Methods] Sixty outpatients (30 per group) with complex regional pain syndrome participated. They received 15 treatment 5 days per week for 3 weeks. The outcome measures were the visual analogue scale for pain, edema, range of motion of the wrist (flexion and extension), fingertip-to-distal palmar crease distance, hand grip strength, and pinch strength. All parameters were measured at baseline (week 0) and at the trial end (week 3). [Results] There were significant improvements in all parameters after therapy in both groups. The whirlpool bath group showed significantly better improvements in the visual analogue score, hand edema, hand grip strength, wrist range of motion (both flexion and extension), fingertip-to-distal palmar crease distance, and the three-point and fingertip pinch strengths than the neuromuscular electrical stimulation group; however, the lateral pinch strengths were similar. [Conclusion] Both whirlpool bath and neuromuscular electrical stimulation are effective in the treatment of complex regional pain syndrome, but the efficacy of the whirlpool bath treatment was better.

Evaluation of Peripapillary Retinal Nerve Fiber Layer Thickness in Patients With Vitamin B12 Deficiency Using Spectral Domain Optical Coherence Tomography

Purpose: To compare peripapillary retinal nerve fiber layer (RNFL) thicknesses measured by Cirrus HD optical coherence tomography (OCT) of patients with vitamin B12 deficiency with healthy controls and to evaluate the correlation between the peripapillary RNFL thickness and plasma vitamin B12 levels. Materials and Methods: Forty-five patients (19 male and 26 female) with a diagnosis of vitamin B12 deficiency (patient group) and 45 age- and sex- matched healthy subjects (control group) were consecutively enrolled in this study. Average, temporal, nasal, inferior, and superior quadrant peripapillary RNFL thicknesses of each subject were obtained using the Cirrus HD OCT. Disc area (DA) and rim area (RA), central subfield thickness (CST), cube volume (CV), and cube average thickness (CAT) were also measured. Results: Mean age of each group was 33.1 ± 6.5 years (range: 21–45 years). Mean plasma vitamin B12 level was 114.8 ± 34.0 pg/mL in the patient group and was 405.1 ± 20.0 pg/mL in the control group (p < 0.001). The patient and control groups were similar regarding axial length, plasma folate levels, DA, RA, CST, CV, CAT, and RNFL thicknesses in superior, nasal, and inferior quadrants. However, average RNFL and RNFL in temporal quadrant were significantly thinner in the patient group than in the control group (p = 0.013 and p < 0.001, respectively). In addition, temporal (r = 0.356, p = 0.001) and average (r = 0.212, p = 0.045) peripapillary RNFL thicknesses were correlated with plasma vitamin B12 levels. Conclusion: We have shown that, as in other non-glaucomatous optic neuropathies, temporal quadrant RNFL thickness was thinner in patients with vitamin B12 deficiency and it was correlated with plasma vitamin B12 levels. Further studies are warranted to clarify the clinical relevance of these findings and the effects of vitamin B12 replacement therapy.

Coexistence of Systemic Lupus Erythematosus and Familial Mediterranean Fever

Sir, Systemic lupus erythematosus (SLE) is a chronic, systemic, autoimmune disease characterized with fatigue, fever and weight loss, malar rash, arthritis, polyserositis, proteinuria, erythema nodosum, and vasculitic lesions. Familial Mediterranean Fever (FMF) is an autosomal recessive, chronic, autoimmune inflammatory disease characterized by periodic fever, abdominal pain, polyserositis, and arthritis. Here, we present a rare case with concurrent SLE and FMF. A 46-year-old female patient admitted with complaints of recurrent fever, abdominal pain, skin rash, oral aphthous ulcers, fatigue, diffuse joint pain, and morning stiffness. Malar rash, oral ulcers, polyarthritis and diffuse joint pain were observed during physical examination. Her medical and family histories were unremarkable. The abdominal ultrasound was normal. The urine analysis was nonspecific, and the proteinuria levels in the 24-hour urine sample were normal. The blood test results were as follows: serum C-reactive protein 2.3mg/dl; erythrocyte sedimentation rate 47mm/hour; and uric acid; 3.8mg/dl. Kidney and liver function tests were normal. The antinuclear antibodies were positive, while the anti-dsDNA antibody and rheumatoid factor were negative. The patient was diagnosed with SLE based on the American College of Rheumatology diagnostic criteria, and began treatment with hydroxychloroquine and prednisolone. The patient’s symptoms decreased after treatment, although her recurrent fever and abdominal pain attacks continued. Additional tests were performed with consideration of a coexistence of another autoimmune disease, and a heterozygous M694V mutation was found in the MEFV gene. 0.5mg Colchicine three times daily treatment was added to the regimen. The patient had significant improvements in fever and attacks of abdominal pain in the follow-up. SLE and FMF are autoimmune diseases that are often characterized by chronic peritonitis, arthritis and polyserositis. SLE patients often have gastrointestinal symptoms, and 8–40% of SLE patients have reported having abdominal pain. The abdominal pain may be caused by medications that are used to treat SLE-induced pancreatitis, vasculitis, serositis, and acute peritonitis. FMF and SLE have similar clinical signs and symptoms. When FMF occurs with an inflammatory disease such as SLE, the fever attacks and/or serositis are often considered to be signs of SLE, and therefore, the diagnosis of FMF may be overlooked. Fever attacks are seen in both SLE and FMF, but the duration of the attacks are shorter in FMF than in SLE. Arthritis is one of the most important clinical features of FMF, and is seen in 50–70% of FMF patients. In FMF, arthritis is generally seen as acute monoarthritis in the lower extremity, while in SLE, it is usually seen as polyarthritis and arthralgia. The arthritis symptom in our cases was identified as polyarthritis. The MEFV gene mutation associated with FMF has also been found in patients with SLE. The SLE disease activity index score has been correlated with the probability of carrying the mutation. In a Turkish study with 2716 FMF patients, 4 cases (0.1%) of SLE were identified. In conclusion, other autoimmune diseases should be considered in cases when chronic inflammatory disease does not respond to treatment.

Assessment of Neuropathic Pain in Patients with Fibromyalgia Syndrome: A Pilot Study

Objective To evaluate the widespread pain of patients with fibromyalgia syndrome [FMS] with neuropathic pain and to investigate the correlation between widespread pain and the functional status of patients. Methods The study comprised 173 female patients with FMS [mean age, 39.35 ± 7.7 years; range: 20–50 years]. The demographic data, widespread pain index [WPI], symptom severity scale [SSS], and complaint durations of the patients were recorded. Current pain intensity was determined using a visual analog scale for pain [VASp], functional status using the Fibromyalgia Impact Questionnaire [FIQ], and pain characteristics using the McGill Pain Questionnaire [MPQ]. Neuropathic and nociceptive pains were differentiated using Leeds Assessment of Neuropathic Symptoms and Signs [LANSS]. Results The patients reported different types of neuropathic pain: knife-stabbing pain 20.8 percent, burning pain 19.7 percent, and stinging pain 16.8 percent. 52.6 percent of patients showed a LANSS score of ≥12, while 47.4 percent showed <12. The former reported knife-stabbing pain most frequently [22 percent], whereas the latter reported burning pain most frequently [26.8 percent]. The FIQ and VASp scores showed a significant correlation [r = 0.557, P < 0.05]. In contrast, the correlation between the LANSS and VASp scores was poor but significant [r = 0.266, P < 0.05] and that between the FIQ and LANSS scores was very poor, but significant [r = 0.175, P < 0.05]. Conclusion Patients with FMS had high LANSS scores and diffuse neuropathic pain complaints. Their functional status was associated with pain severity. Their assessment for neuropathic pain could guide in the explanation of FMS aetiopathogenesis and in clinical practice.

Are Transitional Vertebra and Spina Bifida Occulta Related with Lumbar Disc Herniation and Clinical Parameters in Young Patients with Chronic Low Back Pain

OBJECTIVE Lumbosacral transitional vertebra (LSTV) and spina bifida occulta (SBO) are widespread within the lumbosacral spine. Their connection to lumbar disc herniation (LDH) and/or lower back pain has been debated in the current literature; however, there is no consensus. The purpose of this study is to evaluate the relationship between the frequency of LSTV and SBO with that of LDH among young patients with chronic lower back pain. STUDY DESIGN Cross-sectional. MATERIALS AND METHODS A total of 1094 patients with lower back pain, aged between 20 and 40 years, with lower back pain history persisting for longer than 12 weeks were studied. All the patients in the study were evaluated with standard pelvic radiographs and lumbar vertebra magnetic resonance imaging. The severity of pain was measured using the visual analog scale, and the effect of lower back pain on daily life activities was measured using the Oswestry disability index. The patients were separated into two groups: Group 1 consisted of patients without LDH, and Group 2 consisted of patients with LDH. Additionally, these two groups were separated into three subgroups: Non-LSTV-SBO, LSTV, and SBO. RESULTS It was determined that LSTV frequency was significantly higher (p=0.004) in the lumbar disc herniation group 2. In addition, the existence of LSTV increased the risk of lower back pain (p<0.001, p<0.001) and disability (p<0.001, p<0.001) in young patients with and without LDH or not. However, the presence of SBO did not increase lower back pain (p=0.251, p=0.200) and disability (p=0.134, p=0.161) in both groups. CONCLUSION A relationship was detected between the frequency of LDH and LSTV in young patients with chronic lower back pain between the ages of 20 and 40 years. Also, the presence of LSTV was found to increase the risk of lower back pain and disability.

Ultrasonographic evaluation of the femoral cartilage thickness in patients with hypothyroidism.

[Purpose] The aim of this study was to investigate the effects of hypothyroidism on femoral cartilage thickness by using ultrasound, which has been found to be useful in the early diagnosis of knee osteoarthritis. [Subjects and Methods] Forty patients diagnosed with hypothyroidism and 30 age-, gender-, smoking status, physical activity-, and body mass index-matched healthy subjects were enrolled. The thickness of the femoral articular cartilage was measured using a 7- to 12-MHz linear probe. Three mid-point measurements were taken from each knee at the lateral condyle, intercondylar area, and medial condyle. [Results] Age, gender, body mass index, smoking status, and physical activity were similar between the groups, but patients with hypothyroidism had thinner femoral cartilage than the healthy controls at all measurement sites. Nonetheless, the differences were not statistically significant (except in the case of the left medial condyle). [Conclusion] Ultrasonographic measurement of femoral cartilage thickness may be useful in the early diagnosis of knee osteoarthritis in patients with hypothyroidism.

Response to a Letter to the Editor Entitled “Low Serum B12 Level Does Not Mean Vit. B12 Deficiency-Problems Related to the Diagnosis of Vitamin B12 Deficiency”

We thank Dr Grzybowski for the interest he has shown in our article entitled ‘‘Evaluation of peripapillary retinal nerve fiber layer thickness in patients with vitamin B12 deficiency using spectral domain optical coherence tomography’’. Firstly, Dr Grzybowski argues that low serum vitamin B12 level is not automatically diagnostic for vitamin B12 deficiency in asymptomatic, hematologically normal patients. He states that the clinical picture is crucial for determination of the vitamin B12 deficiency. In addition, he says that the levels of the other biomarkers such as methylmalonic acid or homocysteine could be used for the diagnosis. In our study, we used serum vitamin B12 levels, clinico-electrophysiological evaluation and spinal magnetic resonance imaging for the diagnosis of vitamin B12 deficiency and related neuropathies. Eight patients had clinical vitamin B12 deficiency. However, the rest of the patients (37 patients) had subclinical cobalamin deficiency (SCCD). They were hematologically normal patients and they had no clinical signs except for the low serum vitamin B12 levels. It is known that the anemia is not seen in the SCCD. Biochemical markers of cobalamin status have largely confirmatory roles in the diagnosis of clinical deficiency of vitamin B12, whose clinical expressions provide the diagnostic quasi-gold standard. Cobalamin measurement is generally sufficient for the diagnosis because it has more than 90–95% sensitivity in the clinical deficiency. On the other hand, the diagnosis of SCCD depends completely on metabolic testing because the patients are clinically normal. However, the optimal testing for diagnosis of SCCD continues to be investigated. As recently reported, all biomarkers can produce falsely abnormal results, and none is a diagnostic gold standard. Secondly, Dr Grzybowski points out that the reason for vitamin B12 deficiency in our patients was not given and intrinsic factor (IF)-related malabsorption was not verified. The cause of vitamin B12 deficiency and IF was not evaluated in our work because it has been shown that the causes of SCCD are unknown in more than 60% of cases. As Dr Grzybowski states, there are some problems with the diagnosis of vitamin B12 diagnosis. He has enriched our article by discussing these problems throughout his letter. We, sincerely thank him for his contribution to our work.

Atypical Skin Rash in a Patient with Adult-Onset Still's Disease: A Case Report

Adult-onset Stills disease (AOSD) is an uncommon idiopathic disorder with various clinical manifestations. The absence of specific serological and pathological findings often makes the disease difficult to diagnose. The presence of skin lesions is important to the correct diagnosis of the disease. Various atypical skin lesions have been reported in association with Adult-onset Stills disease. We present a 52-year-old male who had atypical cutaneous manifestations of Adult-onset Stills disease. The rash manifested as persistent, pruritic, dark reddish, confluent, erythematous maculopapules and plaques on his chest, abdomen, upper back and proximal extremities. He suffered high, spiking fevers and had marked elevations of ferritin, C-reactive protein, and the erythrocyte sedimentation rate, which are characteristic of Adult-onset Stills disease. The fever and systemic symptoms improved after the administration of intravenous pulse methylprednisolone therapy. The skin lesions improved after prednisolone and methotrexate combination therapy. Therefore, to make the correct diagnosis, it is important to understand that patients with Adult-onset Stills disease may present with various types of skin lesions.