Taskin Senturk

Oral Versus Intramuscular Cobalamin Treatment in Megaloblastic Anemia: A Single-Center, Prospective, Randomized, Open-Label Study

BACKGROUND Cobalamin (vitamin B12) deficiency, the most common cause of megaloblastic anemia, is treated with intramuscular (IM) cobalamin. It has been suggested by some investigators that oral (p.o.) cobalamin treatment may be as effective in the treatment of this condition, with the advantages of ease of administration and lower cost. OBJECTIVE This study assessed the effects and cost of p.o. versus i.m. cobalamin treatment in patients with megaloblastic anemia due to cobalamin deficiency. METHODS This was a 90-day, prospective, randomized, open-label study conducted at the Division of Hematology, Department of Internal Medicine, Adnan Menderes University Research and Practice Hospital (Aydin, Turkey). Patients aged > or =16 years with megaloblastic anemia due to cobalamin deficiency were randomized to receive 1000-microg cobalamin p.o. once daily for 10 days (p.o. group) or 1000-microg cobalamin i.m. once daily for 10 days (i.m. group). After 10 days, both treatments were administered once a week for 4 weeks, and after that, once a month for life. Patients were assessed for the presence of reticulocytosis between treatment days 5 and 10 until it was detected. Therapeutic effectiveness was assessed by measuring hematologic parameters on days 0, 10, 30, and 90 and serum vitamin B12 concentration on days 0 and 90. The Mini-Mental State Examination was used before and after the B12 therapy for cognitive function assessment and 125-Hz diapozone was used for vibration threshold testing. Neurologic sensory assessment, including soft-touch and pinprick examinations, was used to identify neuropathy at baseline and study end. Tolerability was assessed using laboratory tests and patient interview. Cost was assessed using the cost of the study drug and of the injection. RESULTS Sixty patients completed the study 26 in the p.o. group (16 men, 10 women; mean [SD] age, 60 [15] years) and 34 in the i.m. group (17 men, 17 women; mean [SD] age, 64 [10] years). Reticulocytosis was observed in all patients. In the p.o. group, at days 30 and 90, all hematologic parameters changed significantly versus day 0 (mean hemoglobin levels increased [both P<0.001]; mean corpuscular volume decreased [both P<0.001]; mean white blood cell count increased [day 30, P<0.01; day 90, P<0.001]; and mean platelet count increased [both P<0.001]). The mean serum vitamin B12 concentration increased significantly from day 0 to 90 (P<0.001). These hematologic parameters and the recovery patterns were similar between the 2 groups. Neurologic findings included sensitive peripheral neuropathy in 9 patients (15.0%), alteration of cognitive function (loss of memory, impaired concentration) in 7 patients (11.7%), and loss of sense of vibration in 5 patients (8.3%). Neurologic improvement was detected in 7 of 9 patients (77.8%) in the p.o. group and 9 of 12 patients (75.0%) in the i.m. group at day 30. CONCLUSIONS In this study of patients with megaloblastic anemia due to cobalamin deficiency, p.o. cobalamin treatment was as effective as i.m. cobalamin treatment. P.o. treatment also was better tolerated and less expensive compared with IM treatment. However, because of the small sample size and the short term of this study, further long-term studies are needed to determine the efficacy of p.o. cobalamin treatment.

Diastolic dysfunction in rheumatoid arthritis and duration of disease

Dear Editor, The article entitled “Diastolic heart function in RA patients” written by Wislowska et al. and published in one of the recent issues of your journal was quite interesting [1]. There is no good deWnition for early Rheumatoid arthritis (RA). Early disease has been taken as a symptom with duration of less than 2 year (more conventionally, a time point of 5 year) [2, 3]. Our study included 82 patients (67 females and 15 males) diagnosed as RA according to criteria of ARA and 47 healthy control subjects (31 females and 16 males). In our study, duration of disease was ranging from 1 to 30 years in the patients with RA and mean duration of the disease was 4.8 § 5.2 years. All the patients and control subjects were evaluated prior to the initiation of the study for previous cardiac disease as exclusion criteria. Thus, our study used tissue Doppler and Vp (velocity of Xow propagation) methods in addition to conventional pulse wave Doppler method in order to detect diastolic dysfunction. We categorized the patients into two groups as those with disease duration of less and more than 5 years (early and late RA), there were a signiWcant diVerence between two groups in mitral E/A ratio, tissue Doppler mitral annulus E /A ratio and Vp values (Table 1) [4]. The other study conWrms a high frequency of left ventricular diastolic dysfunction characterised by impaired E/A ratio, prolonged Isovolemic relaxation time (IVRT) and increased late diastole Xow velocity in patients with RA without evident cardiovascular disease. The correlation between transmitral Xow alteration and disease duration suggests a subclinical myocardial involvement with disease progression [5].

Hajdu-Cheney syndrome with ventricular septal defect.

Hajdu-Cheney syndrome (HCS) is a rare osteolysis syndrome characterized by generalized, progressive osteoporosis and acroosteolysis [1]. Cardiovascular abnormalities, including patent ductus arteriosus or atrial or ventricular septal defect (VSD) might be rarely accompanied by HCS as case presentations [2]. We present here a case of HCS with cardiovascular defect that has not been reported previously in the literature. A 31-year-old man presented to our clinic with a nonhealing wound on the plantar surface of his left foot. He had a history of right below-knee amputation, surgical closure of VSD, and spontaneous autoamputation of the right metatarsophalangeal joint and the first, third, and fourth distal phalanges of the left foot. His general condition was stable with blood pressure of 120/80 mmHg, pulse

MPO-ANCA-Associated Small Vessel Vasculitis Presenting as Fever of Unknown Origin

Microscopic polyangiitis (MPA) is an antineutrophil cytoplasmic antibody (ANCA) associated small vessel vasculitis which can present with various clinical manifestations, for which the mainstay of treatment is systemic corticosteroids and immunosuppressants. We report a case of a 54-year-old female admitted to the hospital because of fever during the last month, leukocytosis and elevated erythrocyte sedimentation rate. Persistence of elevated serum creatinine levels and accompanying hematuria led us to perform a renal biopsy, and MPA was diagnosed on the basis of light and immunofluorescence microscopy. Remission was induced with oral corticosteroids and cyclophosphamide therapy in conjunction with plasmapheresis (PF). The objective of this report was to assess the role of PF in the treatment of MPA and report on its utility in patients with MPA who are not responding to standard therapy or who require unacceptably high doses of steroids or immunosuppressants. In a patient presenting with fever of unknown origin, microscopic polyangiitis should also be considered in the differential diagnosis.

Migratory Nodules in the Lung: Lymphomatoid Granulomatosis

A 45-year-old woman was admitted with complaints of non-productive cough, chest pain, fatigue and weight loss in the last 4 months. On physical examination moderate hepatosplenomegaly and crackles most notably on the basal region of the right lung were evident. Serial chest X-rays and computed tomographies revealed a migratory nodular infiltration pattern, changing in location and size in both the lungs. The histopathological diagnosis of the open lung biopsy was lymphomatoid granulomatosis (LG) with a marked angioinvasive lymphocytic perivascular and peribronchial infiltration pattern. In the immunohistochemical analyses LCA, CD-79, CD-20 were positive, while CD-30 was negative. No response could have been achieved under combination chemotherapy and the patient died from progressive disease. LG is a rare disease and a difficult diagnosis in the routine clinical practice. This report emphasises that, LG should be considered especially when there are migratory nodules of varying sizes in lungs.

Rituximab therapy in rheumatoid arthritis and primary biliary cholangitis

The prevalence of rheumatoid arthritis (RA) has been reported to be 1.8% in patients with primary biliary cholangitis (PBC), and mitochondrial antibodies (AMA) have been found in 10% of RA patients.1,2 It was reported that T and B cells play an important role in the inflammatory process of both RA and PBC.3,4 The potential therapeutic target is determined by the pathogenetic mechanism. We report a case series of patients with RA and PBC with good clinical response to rituximab. The first case was a 61-year-old female with the diagnosis of RA and PBC. The serological tests were negative, except for rheumatoid factor (RF), anti-cyclic citrullinated peptide antibodies (anti-CCP) and AMA-M2. Serum lipids, glucose, renal function tests, parathyroid-thyroid hormones, viral markers and protein electrophoresis pattern were normal. Abdominal ultrasonography showed no pathology. She had a medical history of smoking and receiving ursodeoxycholic acid (15 mg/kg/day), methotrexate (MTX, 15 mg/week), hydroxychloroquine (200 mg/day) and methylprednisolone (4–8 mg/day). Due to high disease activity (DAS-28: 6.24) rituximab (1000 mg IV every 2 weeks) was administered. The second case was a 68-year-old female with the diagnosis of RA and PBC. She had medical history of using ursodeoxycholic acid (10 mg/kg/day), leflunomide (20 mg/day), hydroxychloroquine (200 mg/day) and prednisone (10 mg/day). She had a RF of 34.2 U/mL (3–18 IU/mL) and anti-CCP of 8.7 U/mL (0–4.99 U/mL). AMA-M2 was positive and viral serology was negative. Abdominal ultrasonography showed no pathology. Due to exacerbation of

ABO blood groups and rheumatic diseases

Objective Various genetic and environmental risk factors have been shown to be associated with the incidence of rheumatic diseases. However, the pathogenesis of rheumatic diseases poorly understood. Several studies have shown associations of ABO blood groups with various diseases. Our study aimed to determine whether there is an association between the types of rheumatic diseases and ABO and Rh blood groups. Material and Methods The study included the patients, followed up at the Immunology-Rheumatology clinic between January 2016 and December 2016 for diagnosis of rheumatic disease, who had an ABO Rh blood data. Age, gender, type of rheumatic disease, ABO Rh blood groups were recorded. Results When 823 patients were assessed for blood types, 42.5% patients had A type, 33.2% had O type, 15.4% had B type, and 8.9% had AB type. There was significant difference in the distribution of blood types in rheumatic diseases. While SpA, vasculitis, UCTD, Behçets and RA were more common in the patients with A blood type; FMF, SLE, SSc and SjS were more common in the patients with O blood type. In addition, the blood type where all the diseases are observed the least commonly was AB. There was significant difference in the distribution of Rh factor in rheumatic diseases. 92.2% patients were Rh positive and 7.8% patients were Rh negative. Conclusion In our study, we thought that the higher incidence of different rheumatic diseases in different blood types was associated with different genetic predisposition.

Multiple pulmonary rheumatoid nodules.

We present a case of 45-year-old female patient with the diagnosis of seropositive rheumatoid arthritis, who was admitted to our rheumatology department with exacerbation of the disease. The patients disease activity score (DAS 28) was 6.9. Physical examination revealed changes in the lung auscultation as a rough breathing sound at the middle and lower lobe of the right lung. Chest X-ray revealed multiple nodular densities in both lungs. Lung biopsy was performed for the diagnosis and revealed necrotizing granulomas with central fibrinoid necrosis surrounded by epithelioid cells. Such a histopathological picture is typical for rheumatoid nodules. Finally the patient was treated with rituximab, with significant improvement.

Zoledronic Acid Effective as Rescue Treatment for Ankylosing Spondylitis Refractory to TNF Inhibition

Ankylosing spondylitis (AS) is an inflammatory, chronic rheumatic disease that primarily affects the sacroiliac, peripheral joints, and axial skeleton. Genetic, environmental factors, HLA-B27, and cytokines play an important role in the pathogenesis. The main clinical manifestation of disease is inflammatory chronic back pain. The Bath AS Disease Activity Index (BASDAI), Bath AS Functional Index (BASFI), and Assessment of SpondyloArthritis International Society (ASAS) instrument are useful instruments for assessing disease activity in AS. Although nonsteroidal anti-inflammatory drugs are effective for axial-peripheral joints, sulfasalazine for peripheral joints, and tumor necrosis factor-α (TNF-α) blockers for active and resistant AS, clinical response cannot be obtained in many patients. At this stage, various drugs such as abatacept, anakinra, rituximab, tocilizumab, or bisphosphonates have been investigated for refractory patients. There are limited studies about the use of bisphosphonates in patients with AS. We present here the case of a 47-year-old male patient with refractory AS who had clinical and laboratory response with zoledronic acid. A 47-year-old male patient was followed in our clinic with the diagnosis of AS. His general condition was stable, with blood pressure of 110/65 mm Hg and pulse rate of 72/ min; he had a fever of 36.8°C. He had inflammatory upperand low-back pain without peripheral arthritis that negatively affected his quality of life. X-ray of the pelvis showed grade III bilateral sacroileitis. There was no medical history of malignancy, amyloidosis, and comorbid diseases except for AS. He had a medical history of taking etanercept (50 mg once a week, 12 months), adalimumab (40 mg every 2 weeks, 9 months), golimumab (50 mg once a month, 12 months), and infliximab (5 mg/kg every 6 weeks, 9 months) at various points in time for refractory disease. His laboratory test results were as follows: hemoglobin, 12,8 g/dL; mean corpuscular volume, 92 fL; neutrophil count, 7.6 × 10/μL; thrombocyte count, 514 000/μL; erythrocyte sedimentation rate, 81 mm/h, C-reactive protein, 62.3 mg/dL. The patient’s renal tests, liver function tests, electrolytes, autoantibody, and thyroid hormone levels were within normal limits, and the urine test was negative for proteinuria. The BASDAI score was 6.4, and the BASFI score was 7.3. Abdominal ultrasonography revealed hepatosteatosis, and chest X ray was normal. We planned to start zolendronic acid (4 mg, once a year, intravenously) because of active disease with the treatment of infliximab 5 mg/kg, every 6 weeks. The disease was evaluated after zolendronic acid using clinical and laboratory parameters. Significant differences were observed in both disease activity scores and laboratory parameters compared with baseline. On the third month of zoledronic acid treatment, spinal symptoms, pain, and inflammation were decreased, and erythrocyte sedimentation rate and C-reactive protein level reached 21 mm/h and 1.8 mg/dL, respectively. BASDAI score was 2.1 and BASFI score was 4.7 at the third month. The BASDAI and BASFI scores decreased significantly after the treatment. Also, significant improvement was observed in disease activity index and inflammatory markers at the sixth month of therapy. The patient’s renal and liver function tests, electrolytes, and thyroid hormone levels were also within normal limits in our follow-ups. Bisphosphonates inhibit the osteoclast activity, modulate proinflammatory cytokines, and have anti-inflammatory or immune-modifying effects. These drugs may be used in therapy because of subchondral inflammation of bone marrow in AS. There are a number of studies about bisphosphonate use (generally with pamidronate) in patients with AS and spondyloarthropathies. Substantial improvements were observed in BASDAI scores but not in BASFI scores, Bath AS Metrology Index, C-reactive protein, or erythrocyte sedimentation rate with pamidronate. According to the study by Grover et al, there was no significant improvement in BASFI, pain, and patient global assessment, except for ASAS 20. Viapiana et al reported an open-label, singlecenter study in AS patients treated with neridronate or infliximab. The results showed the effectiveness of neridronate and infliximab for disease activity. Also, zoledronic acid is more potent than pamidronate, but it is unknown whether it improves osteitis in AS. We observed good clinical and laboratory response, and pain, BASDAI and BASFI scores, C-reactive protein level, and erythrocyte sedimentation rate were improved significantly with the treatment. In conclusion, combination of TNF-α blockers with zoledronic acid may be useful in the long term and could act as rescue medication for refractory AS patients. This therapy was effective over the short term for our patient; further controlled studies are required to determine the efficacy of this treatment strategy in all stages of AS (early, late, and refractory disease). 567679 AOPXXX10.1177/1060028014567679Annals of PharmacotherapySargin and Senturk research-article2015

Pustulotic Arthro-Osteitis (Sonozaki Syndrome): A Case Report and Review of Literature

Pustulotic arthro-osteitis (PAO) is a rare chronic inflammatory disease, which has now been classified as a seronegative spondyloarthritis. The sternoclavicular and sternocostal joints, pelvis, vertebra, hip, and long bones are affected. Skin findings of the disease are accepted as a variant of pustular psoriasis, but some authors have suggested that palmoplantar pustulosis (PPP) is a different entity. The synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome should be considered in the differential diagnosis. PAO differs from SAPHO by the absence of hyperostosis and the difference in skin manifestations. Here, we aimed to present a 34-year-old female patient with a diagnosis of PAO with typical skin findings and joint involvement.