Amira A. Shahin

Circulating interleukin-6, soluble interleukin-2 receptors, tumor necrosis factor alpha, and interleukin-10 levels in juvenile chronic arthritis: correlations with soft tissue vascularity assessed by power Doppler sonography.

Abstract. Nineteen patients with juvenile chronic arthritis (JCA), ten with systemic (s)-JCA, and nine with polyarticular-onset (p)-JCA were examined for interleukin (IL)-6, tumor necrosis factor (TNF)-α, IL-2R, and IL-10 levels. Power Doppler sonography (PDS) for the more affected knee was used in all of them to evaluate soft tissue vascularity. Serum levels of IL-6 were significantly higher in JCA patients than in controls (P<0.007). Patients with p-JCA showed higher levels of IL-6 than patients with s-JCA, and the difference was statistically nonsignificant. Serum IL-6 levels in all patients correlated significantly with the degree of vascularity detected by PDS (P<0.01). This correlation was more pronounced in p-JCA patients (P<0.01 in p-JCA vs P<0.05 in s-JCA). Serum levels of TNF-α were higher in patients with JCA than in controls (P<0.0001). Serum levels of TNF-α were significantly greater in patients with s-JCA than in p-JCA (P=0.008). Soluble IL-2R levels were higher in patients with JCA than controls (P<0.0002). Serum levels of IL-2R correlated significantly with pannus thickness in p-JCA (P<0.01) and inversely with methoxetrate (MTX) duration in s-JCA (P<0.05). Serum levels of IL-10 were significantly higher in JCA patients than in controls (P<0.0008). Serum IL-10 levels in all patients correlated significantly inversely with hemoglobin levels (r=–0.50, P<0.05), total leukocytic count (TLC) (r=–0.58, P<0.01), and intra-articular steroid injection (r=+0.56, P<0.01). In s-JCA, IL-10 levels correlated significantly with MTX weekly dose (P<0.05). In conclusion, a significant correlation of serum IL-6 levels with the degree of knee joint vascularity was found, and this correlation was more pronounced in p-JCA, which may stress the role of IL-6 as an inducer of neoangiogenesis in JCA.

Prolactin and thyroid hormones in patients with systemic sclerosis: correlations with disease manifestations and activity

Summary.Objective: To determine serum levels of prolactin (PRL) and thyroid hormones and to investigate the correlation between these hormones and different disease manifestations in patients with systemic sclerosis (SSc). Methods: Twenty four patients with SSc (23 women, mean age 37.7±12.7) were subjected to thyroid hormones assessment. Prolactin (PRL) was assessed in 23female patients. The patients were evaluated regarding different disease manifestations. Fifteen normal female volunteers were involved as controls. Results: Serum levels of PRL in all patients was significantly higher than controls (16.75±9.06 for patients vs. 11.6±4.5 for controls with p<0.001). Eight patients out of 23 (34.8%) showed hyperprolactinemia. In patients with diffuse SSc (dSSc), PRL levels showed significant correlation with the rate of skin tethering (r=+0.72, p<0.01) and abnormal left ventricular filling pattern (↓E/A ratio), i.e., occurrence of diastolic dysfunction (r=+0.65, p<0.05). Hyperprolactinemia in all patients correlated significantly with disease duration (r=–0.42, p<0.05).     Mean serum levels of free thyroxin (FT4) in all patients were significantly lower than the control group(7.46±2.7 for patients vs 10.47±2.5 with p<0.001). Eight out of all 24 patients (33.3%) showed hypothyroidism. In groupA (duration<3years); FT4 levels correlated significantly with Dlco% (r=+0.90, p<0.01). While in groupB (duration>3years), T4 hypothyroidism correlated significantly with hand joint restriction of motion (r=+0.66, p<0.01).    Serum levels of triiodothironine (FT3) in all patients were nonsignificantly lower than the control group (4.8±2.3 for patients vs 5.3±1.9 for controls, P=NS). Three patients out of 24 (12.5%) showed T3 thyrotoxicosis. Serum levels of T3 correlated significantly with liver enzyme elevations (r=+0.46, p<0.05) and ESR (r=+0.41, p<0.05). Conclusion: This study demonstrates the close association between PRL or thyroid hormones and some organ involvement in SSc.

Pulmonary function tests, high-resolution computerized tomography, α1-antitrypsin measurement, and early detection of pulmonary involvement in patients with systemic sclerosis

Abstract. Objective. Pulmonary disease represents a major complication of systemic sclerosis (SSc). However, pulmonary involvement is commonly silent. In this study, we investigated the relationship between serum α1-antitrypsin and other means of assessing pulmonary involvement. Methods. Twenty-two patients affected by SSc were studied (mean age 37.6±14.3 years, mean duration of disease 9.9±11.9 years). Fourteen had the diffuse form of disease (dSSc) and eight had the limited form (lSSc). All patients underwent pulmonary function tests, high-resolution computed tomography (HRCT) of the lungs, echocardiography, and serum assessment of α1-antitrypsin. Results. Mean percentage of predicted values of forced vital capacity was lower in patients with dSSc than with lSSc (72.3±17.8 vs 74.5±8, P=NS). Mean percentage of predicted values of forced expiratory volume in 1-s forced vital capacity (FEV1/FVC) was lower in patients with lSSc (79.8±7.5 for lSSc vs 84.4±7.8 for dSSc, P=NS). The overall HRCT score was 5.6±5.9 with no significant difference between disease subgroups. Pulmonary hypertension was detected in two cases, both with dSSc. Alpha1-antitrypsin was significantly higher in patients than in controls (P<0.01), with no significant difference between disease subgroups, and correlated significantly with ground glass opacities in HRCT (P<0.05) and the detection of diffusion defects (r=–0.61, P<0.01). No significant correlation was observed between skin score or degree of dyspnea with HRCT score, lung volume, or carbon monoxide diffusing capacity. Conclusion. Restrictive lung disease was more pronounced in patients with dSSc. Alpha1-antitrypsin levels correlated significantly with ground glass opacities, an early finding of pulmonary involvement in SSc. Extent and severity of skin involvement and degree of dyspnea were not related to pulmonary involvement.

Pulmonary involvement in systemic sclerosis.

Scleroderma, also known as progressive systemic sclerosis (SSc), is a multisystem autoimmune disorder characterized by inflammation and fibrosis involving the skin as well as internal organs such as the vasculature, esophagus, and the respiratory tract. Pulmonary involvement consists most often of interstitial fibrosis and pulmonary vascular disease leading to pulmonary arterial hypertension (PAH). Bronchiectasis is an uncommon pulmonary manifestation of systemic sclerosis. Pulmonary hemorrhage with acute renal failure and diffuse alveolar hemorrhage in the absence of a history of renal involvement or penicillamine intake have rarely been reported in patients with systemic sclerosis.On high resolution CT, evidence of interstitial disease is seen in approximately 90% of patients, the main findings being a fine reticular pattern involving the subpleural regions of the lower lobe. Other common findings include ground-glass opacities, honeycombing, and parenchymal micronodules. The most distinctive pulmonary histologic findings in patients with scleroderma are the vascular changes found in PAH in the absence of significant interstitial fibrosis.There is no strong evidence that any drug alters the course of the two main types of lung disease in systemic sclerosis. This apparent failure of therapy may reflect the fact that pulmonary involvement is usually identified at an established or late stage. It has been suggested that, for fibrosing alveolitis, corticosteroids are most effective if given in combination with cyclophosphamide. In some patients with SSc, PAH has been considered as a major cause of morbidity and mortality. Centrally infused prostacyclin (epoprostenol) and its subcutaneously infused analog treprostinil improve hemodynamics, as well as the quality of life and survival in these patients. Iloprost has also shown a positive effect on PAH in SSc patients. More recently, bosentan, an endothelin receptor antagonist, has proved effective in controlling PAH after 6 months’ treatment. Sildenafil has been used as a selective pulmonary vasodilator in SSc patients with isolated PAH. This drug decreased mean pulmonary artery pressure and pulmonary vascular resistance, and increased cardiac output, with much improvement of the physical condition of the patients. Lung transplant can be considered as a last option.Clinicians must be aware of the possibility of lung disease in patients with SSc so that it can be treated as early as possible.

Thyroid hormones and thyroid-stimulating hormone in Egyptian patients with systemic lupus erythematosus: correlation between secondary hypothyroidism and neuropsychiatric systemic lupus erythematosus syndromes.

Abstract The purpose of this study was to determine the serum levels of thyroid hormones and thyroid-stimulating hormone (TSH), in addition to antithyroglobulin and antimicrosomal antibodies and to investigate the correlation between these hormones and various disease manifestations among Egyptian patients with systemic lupus erythematosus (SLE). A group of 45 patients with SLE (43 women and 2 men with a mean age of 27.57 ± 9.89 years) underment assessment of their thyroid hormones. Antithyroglobulin and antimicrosomal antibodies were assessed in 27 patients. Various disease manifestations were evaluated. A group of 20 normal female volunteers were involved as controls. The mean serum free triiodothyronine (FT3) levels in all patients were significantly lower than in controls (1.89 ± 1.14 vs. 3.15 ± 0.93 pg/ml; P < 0.05). Patients with a history of intravenous pulsed cyclophosphamide therapy showed significantly decreased levels of FT3 compared to those in other patients (1.17 ± 0.5 vs. 2.05 ± 0.95 pg/ml; P = 0.04). The mean serum free thyroxine (FT4) levels in all patients were significantly less than in the control group (1.24 ± 1.22 vs. 1.4 ± 0.3 mg/dl; P < 0.001). Of the 45 patients, 2 (4.4%) were considered to have primary hypothyroidism. Five of six patients (83.3%) with decreased FT4 levels developed fibromyalgia compared to 7 of 39 (17.9%) patients with normal T4 (P = 0.003). The mean serum TSH levels in all patients were significantly higher than in the controls (4.82 ± 22.2 vs. 2.65 ± 1.18 μIU/ml; P < 0.001). Six patients with decreased TSH levels were considered to have secondary hypothyroidism (13.3%); one of them showed decreased T3 and T4, two had decreased T4 only, and the other three were euthyroid. Comparing patients with and without secondary hypothyroidism, showed acute confusion in four (66.7%) in the former group versus four (10.3%) in the latter group (P = 0.006), anxiety in four (66.7%) in the former group versus six (15.4%) in the latter group (P = 0.016), and cognitive disorders in five (83.3%) in the former group versus nine (23.1%) in the latter group (P = 0.008). This study demonstrated evidence of secondary as well as primary hypothyroidism in SLE patients and revealed a close association between thyroid hormones or TSH and some organ involvement in SLE.

Serum Levels of Tissue Inhibitors of Metalloproteinase 2 in Patients With Systemic Sclerosis With Duration More Than 2 Years: Correlation With Cardiac and Pulmonary Abnormalities

In this study, we measured the serum concentration of TIMP-2 in patients with systemic sclerosis (SSc) and explored its possible correlation with cardiac and pulmonary lesions. We studied 42 patients with SSc, with duration equal to or more than 2 years. CT chest, ECG, echocardiography, and serum TIMP-2 concentration measurement using ELISA technique were performed in all patients and in 25 normal controls. The mean serum levels of TIMP-2 in patients was higher than in controls (P = .005). The mean CT score of dSSc patients with elevated TIMP-2 levels was significantly higher than dSSc patients with normal levels (P = .013). Four patients out of five with elevated TIMP-2 levels showed diastolic dysfunction (80%), compared to 2 out of 15 lSSc patients with normal levels (13.3%), with P = .014. Our research, though involving a small group of patients, points to the probable role of TIMP-2 in the development of pulmonary lesions in dSSc patients and cardiac lesions in lSSc patients with duration equal to or more than 2 years.

Symptomatic thrombotic events among Egyptian patients with systemic lupus erythematosus: special consideration for renal vein thrombosis.

Summary.Objective: To evaluate the prevalence of symptomatic thrombotic events among Egyptian patients with systemic lupus erythematosus (SLE), and to evaluate the frequency and the risk factors associated with renal vein thrombosis in those patients. Methods: Fifty-four patients with SLE, 51 (94.4%) females, were involved in this study. All of them were submitted for abdominal sonography, chest X-ray, echocardiography, and Doppler of renal, abdominal and lower limb veins, with examination of data on clinical and laboratory profile. Abdominal CT, brain MRI, MRI both hips, CT chest and pulmonary scintigraphy were used when needed. Results: Sixteen patients (29.6%) were diagnosed with symptomatic thrombotic events. Eight patients had more than one type of thrombosis. Two patients (3.7%) were diagnosed by Doppler as having renal vein thrombosis (RVT). This was confirmed by abdominal CT. One of them presented with nephrotic syndrome, graded by renal biopsy as World Health Organization (WHO) class V, and had positive anticardiolipin antibodies (ACL). The other patient had RVT and inferior vena cava (IVC) thrombosis, nephrotic syndrome, positive ACL, and died before renal biopsy was performed. Both of them were without history of peripheral thrombotic events. One patient was diagnosed with IVC thrombosis, lupus nephritis grade II, positive ACL, and diagnosed by abdominal CT. One patient was diagnosed with portal vein thrombosis and had positive ACL. One patient with retinal vessel thrombosis and positive ACL. Four patients had deep vein thrombosis (DVT). Recurrent miscarriages were reported in 4 patients (7.4%), skin ulcerations in 3 (5.6%), avascular necrosis of the hips in 4 (7.4%), stroke in 1 (1.9%), and pulmonary hypertension in 2 patients (3.7%). Conclusion: Sixteen SLE patients (29.6%) were diagnosed with symptomatic thrombotic events. RVT was detected in 2 patients representing 3.7% of all patients, and 12.5% of patients with thrombosis. Both patients with RVT presented with nephrotic syndrome.

Tumor necrosis factor-alpha and neuropsychiatric lupus erythematosus: relation to single photon emission computed tomography findings

Abstract This study was designed to highlight the relation of tumor necrosis factor-α (TNF-α) to neuropsychiatric lupus (NPLE) manifestations. The relation of TNF-α to the type of single photon emission computed tomography (SPECT) findings in this context was also studied. Twenty-one systemic lupus erythematosus (SLE) females, mean age 27.57 ± 9.89 years, and twenty age-matched normal females (controls), were subjected to TNF-α assessment. Different clinical and neuropsychiatric manifestations were evaluated. SPECT was carried out for all patients. The results showed that the mean TNF-α level (pg/ml) was significantly raised in patients compared with controls (167.8 ± 102.5 versus 64 ± 50.2, respectively, P < 0.005). Thirteen patients (69.1%) had NPLE manifestations. NPLE patients had a significantly higher mean TNF-α than patients without NPLE (203 ± 102.8 versus 109 ± 47.3, respectively, P < 0.03). Positive SPECT findings were found in 18 lupus patients (85.7%), including all 13 patients with NPLE (100% sensitivity), with a multiple focal pattern of hypoperfusion being the most frequent type (9/13), followed by diffuse (3/13), and then single focal pattern (1/13). The mean TNF-α was significantly higher in patients with multiple focal pattern (P < 0.001). In conclusion, results of this work support the hypothesis that TNF-α could be involved in the pathogenesis of NPLE, and hence, it could be speculated that the evolving anti-TNF therapy can play a potential role in the management of this disease.

Arthritis and osteonecrosis in a patient with thrombophilia

This case report describes a very rare entity of thrombophilia manifesting as persistent arthritis and digital ulcers. A 9-year-old Egyptian girl presented with a 2-year history of persistent arthritis and digital ulcers. The case was followed up after 4 years. The clinical manifestations and laboratory investigations are recorded. Thrombophilia with partial protein C deficiency appeared to be responsible for the clinical manifestations with underlying ipsilateral osteonecrosis of patella and calcaneum and resorption of the terminal phalanges. Her older sister showed the same picture with additional pulmonary hypertension. In conclusion, arthritis and osteonecrosis appear as a rare presentation of thrombophilia and protein C deficiency, and ignorance of this may lead to misdiagnosis or confusion with other childhood rheumatic diseases.

Clinical and immunological pattern and outcome of Egyptian systemic lupus erythematosus patients: a single center experience:

Objective The objective of this study was to describe the clinical and immunological pattern and disease outcome in Egyptian systemic lupus erythematosus patients. Patients and methods The medical records of 770 systemic lupus erythematosus patients who were followed from 2002–2015 at Kasr Alainy Hospital, Cairo University, were retrospectively reviewed. Results There were 707 (91.8%) females. The mean age at disease onset was 22.1 ± 8.6 and the disease duration was 6.1 ± 4.5 years. The main clinical manifestations were mucocutaneous (90.8% with oral ulcers affecting 52.5%), arthritis (80.3%), nephritis (67.8%), hematologic involvement (64.9%), serositis (55.2%) and neuropsychiatric manifestations (44.3%). The frequencies of antinuclear antibodies were 94.3%, anti-dsDNA 74.8%, anti-Smith 11%, anticardiolipin antibodies 29.5% and lupus anticoagulant 19.8%. Infections, predominantly bacterial, affected 337 (43.8%) patients. Thirty-three (4.3%) patients died. The main causes of death were sepsis and disease activity. The five- and 10-year survival rates for the total cohort were 97.4% and 96.3%, respectively, and were 96% and 92%, respectively for those with nephritis (p = 0.008). Autoimmune hemolytic anemia, thrombocytopenia, elevated serum creatinine, a higher damage index, infections, a higher glucocorticoid dose and cyclophosphamide use ≥ six months were associated with an increased risk of mortality with odds ratios of 3.69, p < 0.01; 4.12, p < 0.001; 1.54, p < 0.001; 1.43, p < 0.001; 5.08, p < 0.001; 5.04, p < 0.001 and 2.25, p = 0.03, respectively. Conclusion Compared to other cohorts, a relatively lower mean age at systemic lupus erythematosus onset and higher frequencies of oral ulcers, serositis and nephritis were found.