Lupus nephritis presenting with massive ascites and pleural effusion (pseudo-pseudo Meigs' syndrome).

The triad of ascites, pleural effusion, and elevated cancer antigen-125 (CA-125) levels in the absence of ovarian malignancy in systemic lupus erythematosus patients is specifically named pseudo-pseudo Meigs' syndrome (PPMS) or Tjalma syndrome. In this case we reported a 33 years female patient with pleural effusion lasting for 3 years and new onset progressive massive ascites and increased level of CA-125. After she was evaluated for an underlying benign and malign ovarian tumor or any other malignancies, serologic tests were requested with respect to progressive renal dysfunction, proteinuria, lymphopenia, anemia, and effusion. She was diagnosed with systemic lupus erythamatosus (SLE) and renal biopsy showed class-V lupus nephritis. Immunosuppressive treatment led to improvement in both SLE activity and components of PPMS, including massive ascites and pleural effusion and without the need of diuretics. Co-existence of unexplained CA-125 increase, pleural effusion, and ascites might be related to PPMS and detailed examination to exclude malignancy and early and effective treatment of SLE are the mainstay of management.

Unveiling cancer risk in ANCA-associated vasculitis: result from the Turkish Vasculitis Study Group (TRVaS).

To investigate cancer incidence in patients with ANCA-associated vasculitis (AAV), compare it with the age/sex-specific cancer risk of the Turkish population, and explore independent risk factors associated with cancer. This multicenter, incidence case-control study was conducted using the TRVaS registry. AAV patients without cancer history before AAV diagnosis were included. Demographic and AAV-related data of patients with and without an incident cancer were compared. Standardized cancer incidence rates were calculated using age-/sex-specific 2017 Turkish National Cancer Registry data for cancers (excluding non-melanoma skin cancers). Cox regression was performed to find factors related to incident cancers in AAV patients. Of 461 AAV patients (236 [51.2%] male), 19 had incident cancers after 2022.8 patient-years follow-up. Median (IQR) disease duration was 3.4 (5.5) years, and 58 (12.6%) patients died [7 with cancer and one without cancer (log-rank, p = 0.04)]. Cancer-diagnosed patients were older, mostly male, and more likely to have anti-PR3-ANCA positivity. The cumulative cyclophosphamide dose was similar in patients with and without cancer. Overall cancer risk in AAV was 2.1 (SIR) ((1.3-3.2), p = 0.004); lung and head-neck [primary target sites for AAV] cancers were the most common. In Cox regression, male sex and ≥ 60 years of age at AAV diagnosis were associated with increased cancer risk, while receiving rituximab was associated with decreased cancer risk. Cancer risk was 2.1 times higher in AAV patients than the age-/sex-specific cancer risk of the Turkish population population, despite a high rate of rituximab use and lower dose of cyclophosphamide doses. Vigilance in cancer screening for AAV patients covering lung, genitourinary, and head-neck regions, particularly in males and the elderly, is vital.

Successful treatment of a rheumatoid arthritis patient with severe synovial hypertrophy and impaired shoulder function with microwave ablation technique.

Rheumatoid arthritis (RA) is a chronic, inflammatory systemic disorder of synovial joints and results in polyarthritis, chronical degeneration, and finally deformities and ankylosis in severe cases. Synovitis and pannus formation are results of inflammatory changes and lead into restriction in joint movement. Shoulders are among the later affected and larger joints and formation of synovitis in early active stages and pannus in later stages might be concluded with frozen shoulder and severe impairment in functionality. These late-term changes cannot be controlled with systemic or local anti-inflammatory agents and synovectomy is chosen in some cases. However, the results are not satisfactory and recurrence is common. In this case report, we presented a case of RA with severe shoulder pain, restricted movement due to synovial hypertrophy, and pannus formation which are resistant to local and systemic interventions and not suitable for surgical or chemical synovectomy. Microwave ablation (MWA) was performed successfully without any complication and she well responded in terms of DAS-28, functional, and pain scores. Range of motion and funcitonal restriction were recovered. This case report describes the use and promising results of MWA in RA with severe synovial hypertrophy and pannus formation even in the absence of active arthritis and effusion. MWA is a safe and minimally invasive technique that can be easily performed in coordinance of rheumatologists and interventional radiologists in proper cases.

A case of Behçet syndrome presenting with acute coronary syndrome.

Cardiac involvement (CI) is rare in Behçet syndrome (BS), but the important point is that CI may be the first manifestation of the disease. The presence of CI worsens the prognosis of BS, so early diagnosis and early initiation of immunosuppressive treatment (IST) are vital. Coronary aneurysm may develop spontaneously in these patients, or any vascular intervention may cause aneurysm with a pathergy-like reaction. The risk of restenosis is high after percutaneous coronary intervention or coronary artery bypass surgery applied without IST. Therefore, it should be kept in mind that IST constitutes the main step of treatment. Herein, we present a young male diagnosed with BS after acute coronary syndrome caused by coronary artery aneurysms and thrombosis.

Characteristics and outcome of ANCA-associated vasculitides induced by anti-thyroid drugs: a multicentre retrospective case-control study.

OBJECTIVE: Data on ANCA-associated vasculitis (AAV) induced by anti-thyroid drugs (ATD) are scarce. We aimed to describe the characteristics and outcome of these patients in comparison to primary AAV. METHODS: We performed a retrospective multicentre study including patients with ATD-induced AAV. We focused on ATD-induced microscopic polyangiitis (MPA) and compared them with primary MPA by matching each case with four controls by gender and year of diagnosis. RESULTS: Forty-five patients with ATD-induced AAV of whom 24 MPA were included. ANCA were positive in 44 patients (98%), including myeloperoxidase (MPO)-ANCA in 21 (47%), proteinase 3 (PR3)-ANCA in six (13%), and double positive MPO- and PR3-ANCA in 15 (33%). Main clinical manifestations were skin involvement (64%), arthralgia (51%) and glomerulonephritis (20%). ATD was discontinued in 98% of cases, allowing vasculitis remission in seven (16%). All the remaining patients achieved remission after glucocorticoids, in combination with rituximab in 11 (30%) or cyclophosphamide in four (11%). ATD were reintroduced in seven cases (16%) without any subsequent relapse. Compared with 96 matched primary MPA, ATD-induced MPA were younger at diagnosis (48 vs 65 years, P < 0.001), had more frequent cutaneous involvement (54 vs 25%, P = 0.007), but less frequent kidney (38 vs 73%, P = 0.02), and a lower risk of relapse (adjusted HR 0.07; 95% CI 0.01, 0.65, P = 0.019). CONCLUSION: ATD-induced AAV were mainly MPA with MPO-ANCA, but double MPO- and PR3-ANCA positivity was frequent. The most common manifestations were skin and musculoskeletal manifestations. ATD-induced MPA were less severe and showed a lower risk of relapse than primary MPA.

Tocilizumab as a first line biologic agent in rheumatoid arthritis patients with inadequate response to disease-modifying anti-rheumatic drugs: real life experience from the TReasure Registry.

OBJECTIVES: To evaluate the retention rate, treatment response and safety of tocilizumab (TCZ) as first-line biologic treatment in rheumatoid arthritis (RA) patients with inadequate response to disease-modifying anti-rheumatic drugs (DMARD-IR). METHODS: The TReasure Registry is a multicentre, web-based registry of RA and spondyloarthritis patients across Turkey. DMARD-IR RA patients who received TCZ as first-line biologic treatment were included in this registry for efficacy and safety. Demographic and clinical data, treatments, and adverse events were collected. Drug retention rate was estimated using Kaplan-Meier analysis. RESULTS: Among 642 RA patients who ever used TCZ, 258 DMARD-IR RA patients (male/female: 18.2%/81.8%, mean age, 54.41 years) received TCZ as first-line biologic. The median disease duration was 97 (range, 60-179) months and the median TCZ treatment duration was 15 (range, 6-28) months. At the 6th and 12th months of TCZ treatment, the decrease in disease activity scores from baseline was significant. The Kaplan-Meier analysis revealed the retention rate of TCZ at the 12th, 24th, 36th, and 60th months as 81.1%, 73.8%, 66.2%, and 63.6%, respectively. Fifty-seven (22%) patients discontinued TCZ; the main reason being primary or secondary inefficacy (n=29). CONCLUSIONS: Over 80% drug retention rate at 12th month of TCZ treatment in this real-world study was concordant with previously conducted TCZ clinical studies. Significant reductions not only in the disease activity score-28 but also in the simplified disease activity index (SDAI) and clinical disease activity index (CDAI) scores, along with health assessment questionnaire (HAQ) scores, supported the impact of TCZ in RA management with a good safety profile.

Epidemiological characteristics of hepatitis B and C in patients with inflammatory arthritis: Implications from treasure database.

Objectives: This study aimed to evaluate the hepatitis B (HBV) and C (HCV) frequency and clinical characteristics among patients with rheumatoid arthritis (RA) or spondyloarthritis (SpA) who receive biological treatments. Patients and methods: The observational study was conducted with patients from the TReasure database, a web-based prospective observational registry collecting data from 17 centers across Türkiye, between December 2017 and June 2021. From this database, 3,147 RA patients (2,502 males, 645 females; median age 56 years; range, 44 to 64 years) and 6,071 SpA patients (2,709 males, 3,362 females; median age 43 years; range, 36 to 52 years) were analyzed in terms of viral hepatitis, patient characteristics, and treatments used. Results: The screening rate for HBV was 97% in RA and 94.2% in SpA patients. Hepatitis B surface antigen (HBsAg) positivity rates were 2.6% and 2%, hepatitis B surface antibody positivity rates were 32.3% and 34%, hepatitis B core antibody positivity rates were 20.3% and 12.5%, HBV DNA (deoxyribonucleic acid) positivity rates were 3.5% and 12.5%, and antibody against HCV positivity rates were 0.8% and 0.3% in RA and SpA patients, respectively. The HBsAg-positive patients were older and had more comorbidities, including hypertension, diabetes, and coronary artery disease. In addition, rheumatoid factor (RF) positivity was more common in HBsAg-positive cases. The most frequently prescribed biologic disease-modifying antirheumatic drugs were adalimumab (28.5%), etanercept (27%), tofacitinib (23.4%), and tocilizumab (21.5%) in the RA group and adalimumab (48.1%), etanercept (31.4%), infliximab (22.6%), and certolizumab (21.1%) in the SpA group. Hepatitis B reactivation was observed in one RA patient during treatment, who received rituximab and prophylaxis with tenofovir. Conclusion: The epidemiological characteristics of patients with rheumatic diseases and viral hepatitis are essential for effective patient management. This study provided the most recent epidemiological characteristics from the prospective TReasure database, one of the comprehensive registries in rheumatology practice.

Low relapse rate in patients with giant cell arteritis in a multi-centre retrospective Turkish Registry.

OBJECTIVES: Glucocorticoids (GC) are widely accepted as the standard first-line treatment for giant cell arteritis (GCA). However, relapse rates are reported up to 80% on GC-only protocol arms in controlled trials of tocilizumab and abatacept in 12-24 months. Herein, we aimed to assess the real-life relapse rates retrospectively in patients with GCA from Turkey. METHODS: We assembled a retrospective cohort of patients with GCA diagnosed according to ACR 1990 criteria from tertiary rheumatology centres in Turkey. All clinical data were abstracted from medical records. Relapse was defined as any new manifestation or increased acutephase response leading to the change of the GC dose or use of a new therapeutic agent by the treating physician. RESULTS: The study included 330 (F/M: 196/134) patients with GCA. The mean age at disease onset was 68.9±9 years. The most frequent symptom was headache. Polymyalgia rheumatica was also present in 81 (24.5%) patients. Elevation of acute phase reactants (ESR>50 mm/h or CRP>5 mg/l) was absent in 25 (7.6%) patients at diagnosis. Temporal artery biopsy was available in 241 (73%) patients, and 180 of them had positive histopathological findings for GCA. For remission induction, GC pulses (250-1000 methylprednisolone mg/3-7 days) were given to 69 (20.9%) patients, with further 0.5-1 mg/kg/day prednisolone continued in the whole group. Immunosuppressives as GC-sparing agents were used in 252 (76.4%) patients. During a follow-up of a median 26.5 (6-190) months, relapses occurred in 49 (18.8%) patients. No confounding factor was observed in relapse rates. GC treatment could be stopped in only 62 (23.8%) patients. Additionally, GC-related side effects developed in 64 (24.6%) patients, and 141 (66.2%) had at least one Vasculitis Damage Index (VDI) damage item present during follow-up. CONCLUSIONS: In this first multi-centre series of GCA from Turkey, we observed that only one-fifth of patients had relapses during a mean follow-up of 26 months, with 76.4% given a GC-sparing IS agent at diagnosis. At the end of follow-up, GC-related side effects developed in one-fourth of patients. Our results suggest that patients with GCA had a low relapse rate in real-life experience of a multi-centre retrospective Turkish registry, however with a significant presence of GC-associated side effects during follow-up.

Does decision tree analysis predict oral ulcer activity-related factors in patients with Behçet's syndrome?

OBJECTIVES: The study aimed to identify the interactions among treatment protocols and oral ulcer activity related factors in patients with Behçet's syndrome (BS) using the Classification and Regression Tree (CART) algorithm. METHODS: In this cross-sectional study, 979 patients with BS were included from16 centres in Turkey, Jordan, Brazil and the United Kingdom. In the CART algorithm, activities of oral ulcer (active vs. inactive), genital ulcer (active vs. inactive), cutaneous involvement (active vs. inactive), musculoskeletal involvement (active vs. inactive), gender (male vs. female), disease severity (mucocutaneous and musculoskeletal involvement vs. major organ involvement), smoking habits (current smoker vs. non-smoker), tooth brushing habits (irregular vs. regular), were input variables. The treatment protocols regarding immunosuppressive (IS) or non-IS medications were the target variable used to split from parent nodes to purer child nodes in the study. RESULTS: In mucocutaneous and musculoskeletal involvement (n=538), the ratio of IS use was higher in patients with irregular toothbrushing (ITB) habits (27.1%) than in patients with regular toothbrushing (RTB) habits (14.2%) in oral ulcer activity. In major organ involvement (n=441), male patients with ITB habits were more likely treated with IS medications compared to those with RTB habits (91.6% vs. 77.6%, respectively). CONCLUSIONS: Male BS patients on IS who have major organ involvement and oral ulcer activity with mucocutaneous and musculoskeletal involvement have irregular toothbrushing habits. Improved oral hygiene practices should be considered to be an integral part for implementing patient empowerment strategies for BS.

Treatment of systemic sclerosis-associated digital ulcers: recommendations of the Turkish Society for Rheumatology.

OBJECTIVES: Digital ulcers (DUs) are associated with a significant burden in systemic sclerosis (SSc) by leading to severe pain, physical disability, and reduced quality of life. This effort aimed to develop recommendations of the Turkish Society for Rheumatology (TRD) on the management of DUs associated with SSc. METHODS: In the first meeting held in December 2020 with the participation of a task force consisting of 23 rheumatologists the scope of the recommendations and research questions were determined. A systematic literature review was conducted by 5 fellows and results were presented to the task force during the second meeting. The Oxford system was used to determine the level of evidence. The preliminary recommendations were discussed, modified, and voted by the task force and then by members of TRD via e-mail invitation allowing personalised access to a web-based questionnaire [SurveyMonkey®]. RESULTS: A total of 23 recommendations under 7 main headings were formulated covering non-pharmacological measures for the prevention of DUs and pharmacological treatments including vasodilators, anti-aggregants, antibiotics, wound care, pain control, and interventions including sympathectomy, botulinum toxin, and surgery. Risk factors, poor prognostic factors, prevention of DU and adverse effects of medical treatments were reported as 4 overarching principles. CONCLUSIONS: These evidence-based recommendations for the management of SSc-associated DUs were developed to provide a useful guide to all physicians who are involved in the care of patients with SSc, as well as to point out unmet needs in this field.

Behcet's Syndrome Resembling Takayasu's Arteritis with the Distribution of Arterial Involvement: A Case Report and Literature Review.

Behcet's syndrome is a variable vessel vasculitis characterized by recurrent oral and genital ulcers with concomitant skin, ocular, neurologic, gastrointestinal, and joint involvement. Herein, we present a patient who was diagnosed with Behcet's syndrome, which with magnetic resonance angiography showed occlusion of the right subclavian artery at the level of the thoracic outlet and reverse flow in the right vertebral artery consistent with subclavian steal syndrome. In addition, partial narrowing was noted in the left renal artery. The distribution of arterial involvement resembled Takayasu's arteritis, although the presence of mucocutaneous lesions, male gender, history of deep vein thrombosis, and HLA-B51 positivity favored a diagnosis of vasculo-Behçet's syndrome. We treated the patient with methylprednisolone and cyclophosphamide. After the regression of vascular inflammation with immunosuppressive therapy, stenting was performed in the left renal artery.

Pulmonary involvement in antineutrophil cytoplasmic antibody-associated vasculitides: A single center experience from Turkey.

OBJECTIVE: Pulmonary involvement is an important cause of mortality and morbidity in antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV). In this study, we aimed to evaluate the type and frequency of pulmonary involvement and investigate the potential relationship between thorax computed tomography (CT) signs and other systemic clinical findings in AAV. METHODS: A total of 63 patients over the age of 18 and diagnosed with AAV were included in this study. Thoracic CT imaging findings and clinical features of the patients at the time of diagnosis were retrospectively evaluated. The frequency and distribution of detected pathological findings on imaging according to disease types, in addition to the relationship of these findings with other systemic findings and disease severity, were analyzed. RESULTS: Of 63 patients, 50 (79.4%) had pulmonary symptoms at the time of presentation. Most frequently observed pulmonary finding of thorax CT was nodular opacity. Consolidation, cavitary nodules, bronchiectasis, emphysema and fibrotic sequelae change were more common in the patients with diagnosis of granulomatosis with polyangiitis. Honeycomb, atelectasis, interstitial pneumonia, pulmonary venous congestion and pleural effusion were more common in the patients with diagnosis of microscopic polyangiitis. Ground-glass appearance, central airway disease, peribronchovascular nodules, pericardial effusion and lymphatic adenomegaly (>10 mm) were more common in the patients with diagnosis of eosinophilic granulomatosis with polyangiitis. Interstitial lung disease, pulmonary hemorrhage and severe lung involvement were found significantly increased in patients with myeloperoxidase antibody (MPO)-ANCA positivity (P < 0.05). CONCLUSION: Lung involvement was detected in almost all of the patients with AAV. Both interstitial lung disease and severe lung involvement were more frequently found in patients with MPO-ANCA positivity compared to other patients. Pulmonary examination by an imaging technique in all patients with AAV may be useful to determine the vasculitis subtype and to determine the extent of the disease. PRACTITIONER POINTS: Pulmonary involvement is quite common in AAV. Every patient with suspected AAV should be examined with imaging for lung involvement, even in the absence of respiratory symptoms. Severe pulmonary involvement is associated with the presence of severe disease and MPO-ANCA positivity.

The predictors of paradoxical reactions, especially psoriasis, to biologic therapy-findings from the TReasure database: a 5-year follow-up study.

OBJECTIVES: The objectives of this study were to assess the clinical characteristics, predictive factors, and practical algorithms of paradoxical reactions (PRs), specifically paradoxical psoriasis (PP). METHODS: The TReasure database is a web-based prospective observational cohort comprised of patients with RA and SpA from 17 centres around Turkey since 2017. A cohort study and a case-control study nestled within the cohort were identified. RESULTS: In total, 2867 RA and 5316 SpA patients were evaluated. The first biologic agent was found to have caused PRs in 60% of the 136 patients (1.66%) who developed the PRs. The median time interval between the PRs and biological onset was 12 months (range 1-132 months, mean 21 months). The most common types of PP, constituting 92.6% of PRs, were pustular (60.3%) and palmoplantar (30.9%). Adalimumab (30.9%), infliximab (19%) and etanercept (17.4%) were the most common agents causing the PP. In the treatment of most PP patients (73.2%), switching biologic agents was favoured, with TNF inhibitor (TNFi) chosen in 46.03% and non-TNFi in 26.9% of cases. The three most frequently selected drugs were etanercept (24.6%), secukinumab (9.5%) and adalimumab (8.7%). Only 5.17% of patients who switched to another TNFi showed progression. The odds ratios (s) for SSZ, HCQ, and LEF use were significantly higher in RA controls than in PP patients (P = 0.033, OR = 0.15; P = 0.012, OR = 0.15; and P = 0.015, OR = 0.13, respectively). In the PP group with SpA, the number of smokers was significantly higher (P = 0.003, OR: 2.0, 95% CI: 1.05, 3.81). CONCLUSION: Contrary to expectations based on earlier research suggesting that paradoxical reactions develop with the class effect of biological agents, the response of patients who were shifted to another TNFi was favourable.

Isolated inferior thyroidal artery vasculitis: A rare cause of neck pain.

Vasculitis is the inflammatory changes in vessels of any size that usually have a systemic involvement with a quite variable clinical presentation affecting various organs. Although systemic presentation is more common, in some cases localized inflammation of vasculature of a single organ or limited branches of aorta are reported. Here we present, an isolated vasculitis of bilateral inferior thyroidal arteries in a female patient aged 49 years, who presented with neck pain and was diagnosed with ultrasonography and computed tomographic angiography. The clinical and imaging findings were managed successfully with glucocorticoid induction and addition of methotrexate to the treatment. Localized forms of vasculitis are rarer and the limited size of the affected area makes diagnostic investigations and management more complicated. Non-invasive imaging modalities rather than conventional angiography provide useful information in a safer and easier way. Isolated vasculitis of thyroidal arteries is an extremely uncommon site and should be excluded in case of unexplained neck pain, even in the presence of normal laboratory examinations, probably because of the size of the involved vessels.

Clinical and laboratory factors associated with bamboo spine in patients with axial spondyloarthritis: are there clues for bamboo spine?

OBJECTIVES: To analyse the clinical and laboratory factors associated with bamboo spine. METHODS: Data of patients fulfilling the 2009 ASAS classification criteria for axial spondyloarthritis, registered in the national, multicentre, longitudinal, and observational database of TReasure was analysed. Radiographs were assessed using the Bath Ankylosing Spondylitis Radiologic Index (BASRI). Data of patients with a bamboo spine (Group 1) was compared to data derived from patients with a longstanding disease of at least 15 years but no syndesmophytes (Group 2). RESULTS: Out of the 5060 patients, 1246 had eligible radiographs. There were 111 patients (8.9%) with a bamboo spine. Male sex was more common among patients with bamboo spine. The median BMI of 27.7 (25.8-31.1) in Group1 was higher than the BMI of 25.9 (22.9-29.2) in Group 2 (p<0.001). Hip arthritis, present or documented by a physician, was more common in Group 1 [(58/108 (53.7%) vs. 35/103 (34%), p=0.004]. There was a tendency towards a more prevalent enthesitis in these patients [29.1% (25/86) vs. 15.9%(11/69), p=0.054]. HLA-B27 status did not differ between groups. Smoking was more prevalent in Group 1. Multivariate logistic regression analysis revealed that male sex, body mass index, hip arthritis, and enthesitis are associated with bamboo spine in axSpA. CONCLUSIONS: Bamboo spine was more common in the male sex and associated with a delay in diagnosis, high BMI, hip involvement, and enthesitis. The constellation of increased body weight, hip arthritis, and enthesitis may imply that mechanical stress contributes to radiographic damage in the presence of chronic inflammation.

VEXAS syndrome with severe multisystem involvement: Rapid recovery after splenectomy.

VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome is a newly defined disorder in which treatment is still unclear. Herein, a patient with VEXAS syndrome who had atypical findings and an interesting treatment course is presented as a case report. He had fatigue, recurrent fever, pulmonary infiltrates, proteinuria, anemia, leucopenia, transient skin rush and increased acute phase reactants. The patient, who could not tolerate corticosteroid tapering, recovered rapidly after diagnostic splenectomy and the pathological examination of the spleen revealed significant findings.

Visceral leishmaniasis in a patient with systemic lupus erythematosus: Dilemma in diagnosis and management.

Patients with systemic lupus erythemasus (SLE) have an increased risk of bacterial, viral, fungal or parasitic infections, especially if they are receiving immunosuppressive therapy. Leishmaniasis is a group of diseases caused by intracellular flagellate protozoan parasites belonging to the genus Leishmania. We present a 48-year-old female patient, diagnosed with SLE many years ago, who presented with high fever and pancytopenia. We thought that the patient's hematologic findings were related to SLE hematologic involvement. However, we investigated other possible causes when there was no response to drugs for the treatment of SLE. A second bone marrow biopsy showed Leishmania amastigotes and the patient was diagnosed with leishmaniasis. The patient was treated with liposomal amphotericin-B (treatment completed at 40 days). She showed rapid clinical improvement and showed no signs of disease after 4 months.