Anxiety and Depression Disorders in Adults on Chronic Hemodialysis.

Mood disorders are common in end-stage renal disease (ESRD) and may increase morbidity and mortality in adults on chronic hemodialysis (HD), affecting their quality of life (QOL). We aimed to investigate the prevalence of and factors associated with anxiety and depression in ESRD patients on chronic HD. Thirty-nine HD patients were assessed for anxiety and depression using the Hospital Anxiety and Depression Scale (HADS) questionnaire. The HADS scores were correlated with demographic, clinical, and laboratory parameters. According to the HADS scores, depression and anxiety were found, respectively, in 11 (28.2%) and in nine (23.1%) patients. Both depression and anxiety were found in four (10.3%) patients. The average depression score was 7.4 ± 4.2; the average anxiety score was 7.7 ± 4.6. The depression score correlated significantly with the number of medications (r = 0.46, P = 0.003) and phosphatase alcalin (r = -0.37; P = 0.022); the anxiety score correlated significantly with the number of medications only (r = 0.36, P = 0.022). The risk factors associated with anxiety were age [odds ratio (OR) = 1.12; 95% confidence interval (CI): 1.01-1.2; P = 0.025] and sleep disturbances (OR = 6.74; 95% CI: 1.49-30.4; P = 0.016), and only diabetes was a risk factor associated with depression (OR = 4.4; 95% CI: 1.94-16.9; P = 0.009). The screening and management of depression and anxiety would improve the QOL of patients on chronic HD.

Granulomatous interstitial nephritis in the military hospital of Morocco: Causes and outcomes.

Granulomatous interstitial nephritis (GIN) is a rare cause of renal failure. Most frequent etiologies are sarcoidosis, drugs, granulomatosis with polyangiitis, and infections agents (particularly renal tuberculosis). The aim of this retrospective study was to evaluate the clinical features, causes, and outcomes of patients with GIN in adult patients in a region of Morocco. All native renal biopsy (January 2008 to December 2017) were reviewed, but only cases of GIN were analyzed. Eleven cases of GIN were identified in this study, constituting 2.7 % of all native renal biopsies performed on this period (n = 407). There were 7 (63.6%) women, and the average age was 44.2 ± 13.9 years. The mean serum creatinine level at the renal biopsy was 39.1 ± 20.7 mg/L. The most common etiology was sarcoidosis (45.4%, n = 5) followed by drug-induced GIN (27.2%, n = 3). A good renal outcome was reported in patients with drug-induced GIN and sarcoidosis. However, no renal recovery was described in patients with other etiologies. One information from our report and the previously studies is that better data collection systems such as biopsy registries are needed to provide data on the epidemiology and treatment of rare kidney diseases.

Retroperitoneal fibrosis in the military hospital of Morocco.

Retroperitoneal fibrosis (RPF) is a rare disease. It is characterized by the presence of fibro-inflammatory tissue involving retroperitoneal structures. The usual mode of presentation of this disease is with lumbar pain, kidney failure, and a biological inflammatory syndrome. The aim of our study is to describe the diagnostic, etiologic, therapeutic aspects and outcomes of RPF in a nephrology unit in Morocco. Twelve cases of RPF were included in our study. The mean age was 57 ± 10 years (32.70). Nine patients were male and three were female. Symptoms were highly variable, dominated by pain that was present in all patients. Venous compressive signs were described in four patients (33.3%), anuria in one patient (8.3%), and hematuria in two patients (16.6%). Laboratory examinations found an inflammatory syndrome in all patients and renal failure in nine patients (75%), with a mean serum creatinine at 35 mg/L ± 8.5. Diagnosis was suspected on the ultrasound data and confirmed by computed tomography or magnetic resonance imaging. RPF was idiopathic in nine patients (75%). It was secondary to aortic aneurysm in one patient (8.3%), Riedel's thyroiditis in one patient (8.3%), and drug induced in another patient (8.3%). All patients received surgical treatment along with corticosteroids. At six months, remission was achieved in nine patients, whereas three others had steroid resistance. These patients were treated by mycophenolate mofetil (MMF) at a dose of 2 g/day; two of them had intestinal intolerance to MMF and thus were treated by tamoxifen at a dose of 40 mg/day. At 24 months, they stabilized their renal function with incomplete regression of the fibrotic plate. No cases of recurrence were observed during the study period.

Cryoglobulinemia in a moroccan nephrology department.

Cryoglobulinemia is a rare cause of kidney disease that occurs in patients with various diseases. Renal involvement often occurs after appearance of various clinical manifestations dominated by purpura and neuropathy. The aim of this study is to describe clinical, biological, and pathological characteristics of cryoglobulinemic glomerulonephritis (GN), as well as treatment and outcome. This is a retrospective study including all patients with positive cryoglobulin test and biopsy-proven GN secondary to cryoglobulinemia. Fourteen patients with cryoglobulinemic GN were collected. Their mean age was 46.92 ± 15.82 years with male predominance (64.28%). Weight loss, fever (71.42%), and purpuric rash (57.14%) were the main extrarenal manifestations. Eight patients presented with nephrotic syndrome (NS), associated with renal impairment in three patients. Four patients had rapidly progressive GN and two patients had acute kidney injury. Renal biopsy, performed in all patients, revealed membranoproliferative GN with glomerular thrombi in all patients. Crescents and necrotizing vasculitis were present in four patients. Hepatitis C virus (HCV) infection was the most common etiology. Antivirals and steroids or other immunosuppressive agents were used in most of the patients. During follow-up, complete response was observed in three patients and partial response was observed in four patients. Five patients had no response with renal injury requiring hemodialysis. NS with hematuria and renal insufficiency were the main clinical manifestations of cryoglobulinemic GN. In our study, HCV infection dominated the etiologies, although not well described earlier. A half of our patients had poor outcome even after antiviral and immunosuppressive therapy.

Renal Histology in Diabetic Patients.

BACKGROUND: The diagnosis of diabetic nephropathy is based on the course of clinical manifestations and renal biopsy. Renal biopsy is usually performed in patients with atypical presentations. OBJECTIVES: This study was performed to analyze various renal histopathological lesions in diabetic patients and to establish a clinicopathological correlation. MATERIALS AND METHODS: In this retrospective study, the authors analyzed renal histology of 40 patients with type 2 diabetes mellitus who presented with atypical features of diabetic renal involvement and underwent renal biopsy at the Military Hospital Mohammed V, Rabat, Morocco, between January 2008 and December 2016. RESULTS: About 60% of the patients had isolated diabetic nephropathy, 35% had isolated nondiabetic renal diseases and 5% had both. Patients with nondiabetic renal diseases had significantly higher hematuria (P = 0.02), shorter duration of diabetes (P = 0.009), higher mean estimated glomerular filtration rate (P = 0.04) and lower prevalence of diabetic retinopathy (P < 0.001). The most common histological lesion in patients with nondiabetic renal diseases was IgA nephropathy (25%). In patients with diabetic nephropathy, the most common histological class was Class III (42.3%). Furthermore, higher histological classes were associated with lower estimated glomerular filtration rate (P < 0.001) as well as higher prevalence of diabetic retinopathy (P = 0.009) and nephrotic proteinuria (P = 0.04). CONCLUSIONS: This study found that in Rabat, Morocco, the most common histopathological lesion in patients with diabetes was diabetic nephropathy. Hematuria, shorter duration of diabetes, higher mean estimated glomerular filtration rate and lower prevalence of diabetic retinopathy were reported among those with nondiabetic renal diseases. These findings are in accord with that of studies from other countries. However, large sample size and long-term follow-up clinical studies are needed to demonstrate the renal pathological implications and renal outcomes in type 2 diabetes mellitus patients with renal involvement.

Acute interstitial nephritis in the military hospital of Morocco: Clinical features and renal outcomes.

Acute interstitial nephritis (AIN) is a common cause of acute kidney injury, possibly with increasing incidence over recent years; therefore, epidemiological studies provide important information for clinical practice and investigations. The aim of this retrospective study was to describe the clinical features and outcome of patients with biopsy-proven AIN in a region of Morocco. All native renal biopsies (January 2008 to December 2017) on adults were reviewed, but only AIN cases were analyzed. Of the 407 renal biopsies performed in this period, 30 patients were included. The mean age of the patients was 47.1 ± 16.7 years; female gender was preponderant (60%). At the time of biopsy, the serum creatinine level was 33.9 ± 11.8 mg/L. The classic triad of fever, skin rash, and eosinophilia occurred in three (10%) patients. The common causes of AIN were drugs in 13 (43.3%) patients followed by autoimmune diseases in 11 (33.3%) patients. At six months postbiopsy, 26.7%, 33.3%, and 40% had partial, complete, and no recovery, respectively. In this study, a good outcome was associated with autoimmune diseases (P = 0.02) and with a higher intensity of interstitial edema (P = 0.01). However, a presence of a granuloma (P = 0.04), a higher percentage of interstitial fibrosis (P <0.01), and glomerulo-sclerosis (P <0.01) were associated with no recovery and steroids seem to have no effect in the recovery (P = 0.14).This information provides a contribution toward understanding the epidemiology of acute renal failure in Africa, with implications in planning future prospective studies.

Rare and unusual case of anti-factor XI antibodies in patient with plasma cell leukemia.

BACKGROUND: The acquired inhibitors of coagulation have been observed in very rare cases of monoclonal gammopathies. We report a very rare case of anti-factor XI antibodies in patient with plasma cell leukemia (PCL). CASE PRESENTATION: This is a 59-year-old male patient without pathological history, admitted to the nephrology department for management of renal insufficiency and anemia syndrome. The history and physical examination revealed stigmata of hemorrhagic syndrome including hemothorax and hemoptysis. The hemostasis assessment showed an isolated prolonged activated partial thromboplastin time (APTT) with APTT ratio = 2.0.The index of circulating anticoagulant (37.2%) revealed the presence of circulating anticoagulants. The normalized dilute Russell viper venom time ratio of 0.99 has highlighted the absence of lupus anticoagulants. The coagulation factors assay objectified the decrease of the factor XI activity corrected by the addition of the control plasma confirming the presence of anti-factor XI autoantibodies. In addition, the blood count showed bicytopenia with non-regenerative normocytic normochromic anemia and thrombocytopenia. The blood smear demonstrated a plasma cell count of 49% (2842/mm3) evoking PCL. The bone marrow was invaded up to 90% by dystrophic plasma cells. The biochemical assessment suggested downstream renal and electrolyte disturbances from exuberant light chain production with abnormalities including hyperuricemia, hypercalcemia, elevated lactate dehydrogenase, non nephrotic-range proteinuria and high level of C reactive protein. The serum protein electrophoresis showed the presence of a monoclonal peak. The serum immunofixation test detects the presence of monoclonal free lambda light chains. He was treated with velcade, thalidomide and dexamethasone. The patient died after 2 weeks despite treatment. CONCLUSION: Both PCL and anti-factor XI inhibitors are two very rare entities. To the best of our knowledge, this is the first reported case of a factor XI inhibitor arising in the setting of PCL. Factor inhibitors should be suspected in patients whose monoclonal gammopathies are accompanied by bleeding manifestations.

The impact of blood flow rate on dialysis dose and phosphate removal in hemodialysis patients.

The inadequacy of dialysis and hyperphosphatemia are both associated with morbidity and mortality in chronic hemodialysis (HD) patients. Blood flow rate (BFR) during HD is one of the important determinants of increasing dialysis dose. The aim of this study was to determine the effect of increasing BFR on dialysis dose and phosphate removal. Forty-four patients were included in a cross-sectional study. Each patient received six consecutive dialysis sessions as follows: three consecutive sessions with a BFR of 250 mL/min, followed by three others with BFR of 350 mL/min without changing the other dialysis parameters. Patients' body weight was recorded, and blood samples (serum urea and phosphate) were collected before and after each dialysis session. For assessing the efficacy of dialysis, urea reduction ratio (URR), Kt/VDiascan (Kt by Diascan and V by Watson), Kt/V Daugirdas (Daugirdas 2nd generation), equilibrated Kt/V, and phosphate reduction rate (PRR) were used. The increase of BFR by 100 mL/min resulted in a significant increase of URR, Kt/V Diascan, Kt/VDaugirdas, equilibrated Kt/V, and PRR: URR; 75.41 ± 5.60; 83.51 ± 6.12; P <0.001), (Kt/VDiascan; 1.28 ± 0.25; 1.55 ± 0.15; P <0.001), (Kt/VDaugirdas; 1.55 ± 0.26; 2.10 ± 0.61; P = 0.001), equilibrated Kt/V; 1.40 ± 0.19; 1.91 ± 0.52; P = 0.001), and (PRR; 50.32 ± 12.22; 63.66 ± 13.10; P = 0.010). Adequate dialysis, defined by single-pool Kt/V ≥1.4, was achieved using two different BFRs: 250 and 350 mL/min, respectively, in 73% and 100% of the cases. Increasing the BFR by 40% is effective in increasing dialysis dose and phosphate reduction rate during high-flux HD. The future prospective studies are needed to evaluate the impact of increasing BFR on phosphate removal using the total amount of phosphate removed, and also evaluate the cardiovascular outcome of phosphate reduction and dialysis improvement.

Histopathological study of nephrotic syndrome in adults: A Moroccan report.

The reported causes of nephrotic syndrome (NS) varies between different countries. In this retrospective study, we aimed to evaluate the underlying causes of NS in adult patients who underwent renal biopsy in a region of Morocco and we also determined the distribution of histopathological diagnoses with regard to the age subgroups and genders from January 2007 to December 2016. Patients were divided into four groups according to age at the time of renal biopsy. A total of the 257 patients with NS were included in this study. The mean age of the patients was 40.9 ± 16.7 years; male gender was preponderant (61.9%). One hundred and sixty-six (64.6 %) and 81 (35.4%) patients were diagnosed as primary and secondary glomerulonephritis, respectively. The most common diagnosis in NS was membranous nephropathy (MN) (22.2%), followed by minimal change disease (MCD) (20.6%), and lupus nephritis (LN) (13.6%). Among the patients aged 15-30, 31-45, 46-60, and >61 years, the most common cause of NS was MCD (32.1%), MN (29.6 %), MN (26.1%), and amyloidosis (AM) (28.2%), respectively. The proportion of patients with MCD and LN decreased in parallel with patient age and the proportion of patients with renal AM increased in parallel with patient age. Among the female patients aged 15-30 and 31-45 years, LN was the leading cause of NS (41.5 and 36.7%, respectively). Among the male patients aged 15-30 years, MCD was the leading cause of NS (43.2%). Our study over 10 years represents an important data of regional variations of glomerular diseases presenting with adult-onset NS.

Complete remission of nephrotic syndrome secondary to amyloid a amyloidosis in patient with inactive Crohn's disease after treatment by infliximab.

Secondary amyloidosis Amyloid A (AA) is an infrequent but a severe complication of Crohn's disease (CD). This complication results from the activity of the underlying inflammation disease to form amyloid fibril deposits in tissues. We present a case of a 34-year-old female patient with CD treated by azathioprine with inactive disease for three years and who developed a nephrotic syndrome secondary to AA amyloidosis. The treatment by infliximab for one year leads to a complete remission of the nephrotic syndrome. In this case, this complication occurred while the patient was clinically well, with biological and endoscopic markers showing an inactive or only mildly active disease. Infliximab could be a useful tool for a successful treatment of amyloidosis secondary to CD.

Late-onset choreoathetotic syndrome following heart surgery in adults with end-stage renal disease.

Choreoathetotic syndrome is a rare complication of open cardiac surgery that is seen usually in children after surgery for congenital cardiac anomalies. Here, we report two cases of adult patients with end-stage renal disease (ESRD) on regular hemodialysis who developed acute choreoathetotic syndrome few days after cardiac surgeries under cardiopulmonary bypass (CPB). Improvement was seen after an interval with complete resolution in one case. Investigations of the cause have been noncontributory. Long CPB time seems to be the main identified risk factor in these cases. One of the unusual features of our adult cases was the existence of ESRD. To the best of our knowledge, this is the first time this complication is described in association with ESRD although the role of this comorbidity in these cases is uncertain.

[Initiating hemodialysis in Morocco: Impact of late referral]. / La mise en hémodialyse au Maroc : intérêt du suivi néphrologique.

INTRODUCTION: End-stage renal disease (ESRD) is a major public health concern in Morocco with an incidence in constant progression according to MAGREDIAL "Morocco Dialysis Registry". Patients are often sent late to nephrologists, which is a source of complications recognized in several countries. For these reasons, we tried to evaluate, in our context, the prevalence and factors of this late referral (LR). METHODS: This is a retrospective study which included all patients initiating hemodialysis between January 2007 and December 2015. We found the history of following these patients and sought their clinical characteristics at the time of setting hemodialysis. RESULTS: During the study, 318 patients were admitted for management of ESRD. Their average age was 54.31 years and diabetic nephropathy was the most common cause of 41% of cases. Only 105 patients (33%) had a nephrological follw up in almost two thirds of cases, hemodialysis was started by using a temporary central venous catheter especially femoral. we have identified five factors associated with LR: nemia, hypoalbuminemia, inflammatory syndrome, a longer initial hospitalization, a greater use of temporary catheterization as first access. CONCLUSION: LR patients with ESRD remains very common in our context. It is about 67% and complicates implementation hemodialysis patients with anemia and more use of central catheters that are predictors of mortality previously described in the literature. Economically, LR significantly increases the cost of care by significantly increasing the duration of hospitalization.

Insomnia in hemodialysis patients: A multicenter study from morocco.

Previous studies have shown that insomnia is a common sleep disorder in patients with end-stage renal disease. This study aims to determine the prevalence and risk factors of insomnia in our chronic hemodialysis (HD) patients. This is a cross-sectional study conducted in three HD units in Morocco. To assess the prevalence of insomnia, we used a specific questionnaire. Patients complaining of difficulty in falling asleep and/or nocturnal awakenings occurring seven nights a week during the last month were included in the group "insomnia;" the other patients were used as controls. Clinical, biological, and dialysis data were recorded for each patient. Sleep disorders and their subjective causes were also identified. Eighty-nine percent of questioned patients admitted to having sleep disturbances of different degrees. Insomnia was significantly associated with female gender and time of dialysis. Age, body mass index, inter-dialytic weight gain, and blood pressure were similar between the two groups, as well as dialytic parameters and drug use. There was no significant difference in the values of plasma creatinine, urea, hemoglobin, parathyroid hormone, calcium, phosphorus, C-reactive protein, and albumin between the groups. Disorders most frequently encountered in patients with insomnia were waking up at night (90%), difficulty falling asleep (60%), and daytime sleepiness (60%). The restless legs syndrome was seen in half of these patients. The main reported causes of insomnia were anxiety and/or depression (70%) and bone pain (67%). Insomnia is common in HD patients and is frequently associated with other disorders of sleep. Female sex and duration on dialysis are the two risk factors found in our study. Insomnia does not appear related to any biochemical or dialysis parameters. Increased attention should be given to the management of dialysis patients regarding the diagnosis and management of insomnia and associated sleep disorders.

Gastrointestinal bleeding due to angiodysplasia in patients on hemodialysis: A single-center study.

Gastrointestinal (GI) bleeding due to angiodysplastic lesions is a common problem among patients receiving hemodialysis (HD). We studied 22 HD patients (5 females and 17 males) who had GI bleeding due to angiodysplasia; the mean age of whom was 54 ± 10 years. All patients had upper and lower GI endoscopy. The most common site for the lesion was the right colon in seven cases (31.8%), followed by stomach in 4 cases (18.1%). In eight (36.3%) patients, there were multiple lesions located in the stomach, duodenum, and the right colon. All patients were treated with coagulation; with argon plasma in 14 (63.6%) patients, bipolar coagulation in five (22.7%) patients, and hot clip in three (13.6%) patients. One patient who presented with persistent bleeding despite endoscopic therapy was well-benefited of a complementary treatment, thalidomide. Hemostasis was obtained in all patients after an average of 6.8 sessions of endoscopic coagulation procedure. We conclude that angiodysplasia is a frequent cause of hemorrhage in chronic renal failure that can be managed in most patients by argon plasma and bipolar coagulation.

Kidney biopsy in the Military Hospital of Morocco: Complications and histopathological findings.

Epidemiological studies on renal biopsies are necessary to establish the pattern and trends of renal diseases in a particular geographic area. In this retrospective study, we reviewed the medical records, histopathology findings and complications of renal biopsy in a region of Morocco. We studied a total of 130 native kidney biopsies taken between January 2008 and January 2012. All biopsies were examined by light microscopy and immunofluorescence microscopy. There were 86 males (66.2%) and 44 females (33.8%), with a mean patient age of 44.82 ± 17.86 (range 8-86) years. The most common indications of renal biopsy was nephritic syndrome (61.5%), followed by renal failure of unknown etiology (30.8%) and asymptomatic urinary abnormalities (5.4%). Primary glomerulonephritis (PGN) was found in 60 (46.2%) of the patients. Among the PGN cases, the most common one was membranous nephropathy (MN) (12.3%). Secondary glomerular disease (SGN) accounted for 48 (36.9%) of the cases. The most common SGN was lupus nephritis (LN) (10%). Tubulointerstitial disease [13 (10%)] and vascular disease [9 (6.9%)] were less common. The most common complications of the procedure were pain at the biopsy site in 12.3%, gross hematuria in 12.3%, perirenal hematoma in 7.7% and hematuria requiring nephrectomy in 0.8% of the patients. The most common indication for renal biopsy was nephrotic syndrome, MN was the most frequent PGN and LN was the most frequent SGN in our report.

Effects of lowering dialysate calcium concentration on mineral metabolism and hemodynamic parameters in hemodialysis patients.

INTRODUCTION: It has been suggested that a dialysate calcium concentration of 1.5 mmol/L is a compromise between bone protection and cardiovascular risk. This study aimed to investigate the effect of reducing dialysate calcium concentration to 1.5 mmol/L on mineral metabolism and hemodynamic parameters. MATERIALS AND METHODS: Dialysate calcium concentration was changed from 1.75 mmol/L to 1.5 mmol/L for 9 months and observed the effects on mineral metabolism and dialysis outcome parameters in 52 hemodialysis patients. RESULTS: The results at 9 months demonstrated that postdialytic serum calcium level decreased significantly from 109 ± 7 mg/L to 102 ± 6 mg/L, intact parathyroid hormone (PTH) increased from 372 ± 52 pg/mL to 606 ± 80 pg/mL, and the oral alfacalcidol increased from 1.4 ± 0.3 µg/w to 3.3 ± 0.4 µg/w. In patients with low PTH levels, continuous increase of PTH was observed. There were no significant variation in the oral calcium carbonate dose and serum levels of alkaline phosphatase, predialytic calcium, and pre- and postdialytic phosphorus. The ultrafiltration rate and postdialysis systolic blood pressure were significantly lower after reducing the dialysate calcium concentration to 1.5 mmol/L. Intradialytic hypotension and cramps were more frequent with this dialysate calcium concentration. CONCLUSIONS: These findings demonstrated that a decrease in dialysate calcium concentration from 1.75 mmol/L to 1.5 mmol/L improved mineral metabolism by prevention of postdialytic hypercalcemia and releasing oversuppression of PTH, but it was associated with more use of oral alfacalcidol and more hemodynamic impairment.

Angio-embolization of a renal pseudoaneurysm complicating a percutaneous renal biopsy: a case report.

We report the treatment of a bleeding renal pseudoaneurysm by angio-embolization. A 21 years old woman developed macroscopic haematuria following renal biopsy. Renal angio-scan showed a 1.4 cm renal pseudoaneurysm in the left kidney. The presence of pseudoaneurysm was confirmed by selective renal angiography. Successful embolization was performed using gelatine sponge particles.

Lupus nephritis emerging during remission of minimal change disease.

INTRODUCTION: Rare cases of association between lupus nephritis (LN) and minimal changes nephrotic syndrome (MCNS) were described. Some authors suggest that this association, taking into account the low prevalence of both diseases, may not be a simple coincidence. Several pathophysiological hypotheses have been proposed to explain this association, including a potential central role of T lymphocytes. CASE REPORT: We describe the case of a 21 years-old female patient who initially presented with isolated nephrotic range proteinuria. She had no evidence of systemic involvement and Immunological tests were negative, including anti-neutrophil antibodies (ANA) and anti-double-stranded DNA antibodies (Anti-dsDNA). Renal biopsy showed normal glomeruli under light microscopy and no significant deposits were found in immunofluorescence studies. She was diagnosed to have MCNS and responded to a short course of steroids. She remained in remission for three years, after which she presented again with nephrotic-range proteinuria accompanied by clinical signs of systemic involvement. During her second presentation, she fulfilled the diagnostic criteria of systemic lupus erythematosus (SLE) and another kidney biopsy showed class-V lupus nephritis. She was treated with pulse steroids followed by oral prednisolone and mycophenolate mofetil, with good clinical response. CONCLUSION: This case indicates that relapses of MCNS should be carefully investigated in the right setting to avoid missing a systemic disease such as SLE.