Evaluation of pediatric rheumatologists' approach to rituximab use: a questionnaire study.

Rituximab (RTX) is a chimeric monoclonal antibody that targets the CD20 antigen on B cells and is used in various autoimmune disorders. In this study, we aimed to measure the awareness of pediatric rheumatologists about the use of RTX through a survey. Between February and March 2023, a 42-question survey was sent via email to pediatric rheumatology specialists in Turkey. The participants were questioned for which diagnoses and system involvement they preferred to use RTX, which routine tests they performed, vaccination policy, and adverse events that occurred during or after infusion. Forty-one pediatric rheumatologists answered the survey. They prescribed RTX most frequently for systemic lupus erythematosus (87.8%) and ANCA-associated vasculitis (9.8%). Prior to the administration of RTX, 95% of clinicians checked renal and liver function tests, as well as immunoglobulin levels. The most frequently tested hepatitis markers before treatment were HBsAg and anti-HBs antibody (97.6%), while 85.4% of rheumatologists checked for anti-HCV. Clinicians (31.4%) reported that they postpone RTX infusion 2 weeks following an inactivated vaccine. Sixty-one percent of rheumatologists reported starting RTX treatment 1 month after live vaccines, while 26.8% waited 6 months. The most frequent adverse events were an allergic reaction during RTX infusion (65.9%), hypogammaglobulinemia (46.3%), and rash (36.6%). In the event of hypogammaglobulinemia after RTX treatment, physicians reported that they frequently (58.5%) continued RTX after intravenous immunoglobulin administration. CONCLUSIONS: RTX has become a common treatment option in pediatric rheumatology in recent years. Treatment management may vary between clinician such as vaccination and routine tests. WHAT IS KNOWN: • During the course of rituximab therapy, clinicians should be attentive to specific considerations in pre-treatment, during administration, and in post-treatment patient monitoring. WHAT IS NEW: • There are differences in practice among clinicians in the management of RTX therapy. These practice disparities have the potential to impact the optimal course of treatment. • This study highlights that standardized guidelines are needed for RTX treatment in pediatric rheumatology, particularly for vaccination policies and routine tests.

The effect of intra-articular steroid injection on the cartilage and tendon thicknesses in juvenile idiopathic arthritis.

BACKGROUND AND AIM: Intra-articular corticosteroid injection (IACI) is a safe first-line or adjunct therapy that can be used in any subtype of juvenile idiopathic arthritis (JIA). However, limited studies evaluated the effect of IACI on cartilage. As a result, our study aimed to examine the distal femoral cartilage thickness of patients with JIA who received IACI to the knee joint using ultrasound imaging. METHODS: We randomly selected JIA patients who performed IACI in the knee joint. Baseline bilateral joint cartilage and tendons thickness were measured. Then, the articulary fluid was aspirated, and intra articulary steroid was injected during the same period. Six months after injection, the exact measurements were repeated. Exclusion criterias were that patients had IACI past six months of the baseline measurement and more than one IACI during the study period.. Distal femoral cartilage thickness, quadriceps tendon thickness, and distal and proximal patellar tendon thicknesses were compared at baseline (before IACI) and six months after IACI. RESULTS: Thirty patients with JIA were included in the study, and 23 (76.7%) were female. The median age was 11 years (interquartile range (IQR), 6 to 14), and the median disease duration was 3.3 years (IQR, 5 months to 5 years). Subtypes of JIA were oligoarticular in 25 (83.3%), polyarticular in 2 (6.7%), enthesitis-related arthritis in 2 (6.7%), and juvenile psoriatic arthritis in 1 (3.3%). Distal femoral cartilage thickness was 2.96±0.79 mm at baseline and 2.85±0.70 mm at six months after IACI (p=0.35). Also, the tendon thicknesses were the similar at six months after baseline measurements. CONCLUSION: Our findings reveal that knee IACI in patients with JIA did not significantly change cartilage and tendons thicknesses. This observation could indicate that IACIs have no detrimental effects on the cartilage and the tendons.

Clinical usefulness of anti-nuclear antibody in childhood: real-world experience at a tertiary care center : Usefulness of ANA in pediatric autoimmune diseases.

We evaluated the reasons for requesting anti-nuclear antibody (ANA) analysis in clinical practice at a tertiary center and the performance of ANA in pediatric autoimmune diseases. Patients under 18 years of age who underwent ANA testing for various symptoms between 2013 and 2017 were included. We retrieved data from medical records, including demographic and clinical characteristics, diagnoses, ANA results, titers, and staining patterns. The performance assessment tools were calculated according to the ANA titer for autoimmune diseases. Risk factors for autoimmune diseases in ANA-positive patients were evaluated using logistic regression analysis. Changes in ANA titer and seroconversion were evaluated using repeated ANA analyses. A total of 3812 patients underwent ANA. Medical records of 3320 patients were obtained. The rate of ANA positivity was 27.4%. ANA was requested most frequently because of musculoskeletal findings in 1355 patients (40.8%). Juvenile idiopathic arthritis (n = 174, 20.2%) was the most common diagnosis in ANA-positive patients, followed by systemic lupus erythematosus (n = 52, 6%). For autoimmune diseases, a titer of ≥ 1:100, a sensitivity of 40.1%, and a specificity of 77.1% were observed. At a titer ≥ 1:1000, the sensitivity and specificity were 24.1% and 89%, respectively. Homogeneous staining was an additional risk factor for autoimmune diseases in ANA-positive patients by multivariate logistic regression analysis (OR [95% CI]: 4.562 [3.076-6.766], p < 0.001).    Conclusion: Our results revealed that the performance of the ANA test in diagnosing autoimmune diseases in pediatric clinical practice was poor. Therefore, clinical findings should be carefully evaluated before ANA testing is performed. What is Known: • ANA can be detected in systemic autoimmune rheumatic diseases. • The diagnostic role of ANA is controversial, especially in childhood. What is New: • One in four patients who requested the ANA test had an autoimmune disease. • Less than half of patients with an autoimmune disease had ANA positivity.

Neuropsychiatric involvement in juvenile-onset systemic lupus erythematosus: A multicenter study.

INTRODUCTION: Neuropsychiatric (NP) involvement is a restricted area in juvenile-onset systemic lupus erythematosus (jSLE). AIM: To investigate the prevalence, demographic and clinical features, and outcomes of the neurological involvement in the Turkish jSLE population. METHODS: This study was based upon 24 referral centers' SLE cohorts, multicenter and multidisciplinary network in Turkey. Patient data were collected by a case report form which was standardized for NP definitions according to American Collage of Rheumatology (ACR). Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI) neuropsychiatric part was used to determine NP damage. Variables were evaluated Ward's hierarchical clustering analyses, univariate, and multivariate logistic regression analyses. RESULTS: A hundred forty-nine of 1107 jSLE patients had NP involvement (13.5%). The most common NPSLE findings were headache (50.3%), seizure (38.3%), and acute confusional state (33.6%). Five clusters were identified with all clinical and laboratory findings. The first two clusters involved neuropathies, demyelinating diseases, aseptic meningitis, and movement disorder. Cluster 3 involved headache, activity markers and other SLE involvements. Idiopathic intracranial hypertension, cerebrovascular disease, cognitive dysfunction, psychiatric disorders and SLE antibodies were in the fourth, and acute confusional state was in the fifth cluster. In multivariate analysis, APA positivity; OR: 2.820, (%95CI: 1.002-7.939), P: 0,050, plasmapheresis; OR: 13.804 (%95CI: 2.785-68.432), P: 0,001, SLEDAI scores; OR: 1.115 (%95CI: (1.049-1.186), P: 0,001 were associated with increased risk for neurologic sequelae. CONCLUSION: We detected the prevalence of juvenile NPSLE manifestations in Turkey. We have identified five clusters that may shed light pathogenesis, treatment and prognosis of NP involvements. We also determined risk factors of neurological sequelae. Our study showed that new definitions NP involvements and sequelae for childhood period are needed.

Evaluation of liver elasticity with shear-wave elastography in juvenile idiopathic arthritis patients receiving methotrexate.

BACKGROUND: Methotrexate (MTX) is the first-choice disease-modifying drug in juvenile idiopathic arthritis (JIA) treatment. Methotrexate is metabolized in the liver and can cause liver toxicity and fibrosis with long-term use. Ultrasound shear wave elastography (SWE) is a non-invasive method and can detect liver fibrosis by evaluating the liver elasticity. The aim of this study was to assess liver stiffness and detect if there is an increase in liver stiffness or fibrosis findings with the non-invasive SWE method in JIA patients under MTX treatment. METHOD: The study included 49 JIA patients under MTX treatment and 48 healthy controls, matched for age and sex with a body mass index below the 95th percentile. The demographic data and clinical characteristics of patients were obtained from medical records. Liver function tests were evaluated, and liver tissue stiffness measurements were performed with SWE. RESULTS: Of the 49 patients, 67.35% were girls and the mean age was 10.69 (±4.33) years. The duration of MTX treatment was 23.00 (1-80) months, and the cumulative dose of MTX was 1,280.867 mg (±934.2) in the patient group. There was no statistically significant difference in liver stiffness between patients receiving MTX and healthy controls (P = 0.313). There was no relationship between MTX duration, cumulative dose, route of administration, and liver stiffness. Only gamma glutamyl transferase values were weakly correlated with liver stiffness (P = 0.029). CONCLUSIONS: We did not detect an increase in liver tissue stiffness in JIA patients using methotrexate in comparison with controls.

The remarkable characteristics of the children with colchicine-resistant familial Mediterranean fever in Turkey.

OBJECTIVES: Colchicine is the fundamental treatment of familial Mediterranean fever (FMF). Still, 5-10% of patients are not in remission with colchicine treatment. A consensus could not be established for the definition of colchicine resistance in FMF. This study aimed to determine factors that help to predict colchicine resistance in pediatric FMF patients. METHODS: Patients with FMF that age of diagnosis was under 18 years old were included in our study. Fifty colchicine responsive and 33 colchicine-resistant patients were stratified as groups 1 and 2, respectively. Patients' clinical and laboratory findings were evaluated. Logistic regression analysis was used to determine the risk factors of colchicine-resistant FMF. Receiver operating characteristic (ROC) curve analysis was used to identify and compare the predictive performances of colchicine-resistant FMF models. RESULTS: Homozygous exon 10 MEFV mutations were frequent in group 2 (Group 1: 34 (68%), group 2: 32 (97%), p = .013). Univariate analysis showed that the age of onset of symptoms, age of diagnosis, chronic arthritis, myalgia and diarrhea during attacks, and the number of attacks, high ISSF and Pras score, high C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) values under colchicine treatment were risk factors for colchicine-resistant FMF. With multivariate analysis, the number of attacks (OR 1.418, CI (95%) 1.149-1.750, p = .001) and high ESR values (OR 1.129, CI (95%) 1.059-1.204, p<.001) were detected as independent risk factors for colchicine-resistant FMF. CONCLUSION: The predictive factors were determined for pediatric colchicine-resistant FMF in our study. The results will help to early diagnosis and treatment of chronic inflammation in FMF.

Unexpected condition in a rare disease: encephalopathy in early-onset sarcoidosis.

BACKGROUND: Granulomatous autoinflammatory diseases are monogenic syndromes caused by mutations in the region encoding the nucleotide-binding domain of the nucleotide-binding oligomerization domain-containing 2 gene. Blau syndrome and early-onset sarcoidosis are familial and sporadic forms of the same disease and are very rare. Many organ systems may be involved; however, neurologic involvement is infrequent. We reported a case of encephalitis in a 12-year-old girl followed with a diagnosis of early-onset sarcoidosis. CASE: The patient was diagnosed with juvenile idiopathic arthritis at 3 years of age. We considered druginduced sarcoidosis at 6 years of age with granulomatous inflammation of liver and kidney. Small joint involvement and camptodactyly developed during follow-up. M315T mutation was detected in the NOD2 gene supporting the diagnosis of early-onset sarcoidosis. The patient suffered from encephalopathy when she was under methotrexate, infliximab, and systemic steroid treatment at 12 years of age. Cerebrospinal fluid limbic encephalitis antibody panel was negative. CONCLUSION: Encephalopathy is not common in Blau syndrome and early-onset sarcoidosis. The cause of encephalopathy in our patient was interpreted as autoimmune encephalitis.

Factors and glucocorticoid usage affecting the prognosis of systemic juvenile idiopathic arthritis.

BACKGROUND: The rate of glucocorticoid (GC) use is significantly higher in systemic juvenile idiopathic arthritis (SJIA) than other juvenile idiopathic arthritis subtypes. There is no consensus on the duration and dosage of GC treatment. We aimed to investigate the risk factors for a polyphasic / persistent disease course and the effect of dose and duration of GC treatment on SJIA prognosis. METHODS: Forty-two patients who were diagnosed with SJIA, and for whom the duration of disease was longer than 2 years, were included. Patients were divided into monophasic and others (polyphasic / persistent disease course). Risk factors for polyphasic / persistent disease course, which were clinical and laboratory findings regarding the patients, treatment options, dose, and duration of GCs, were evaluated for the first active disease periods and for all flares in the entire disease course. RESULTS: Of the 42 SJIA patients, 21 had monophasic, and 21 had polyphasic / persistent disease. Cumulative dosages and durations of glucocorticoid treatment were similar in the two groups at the first flare (odds ratio (OR): 1.032 P: 0.671; OR:1,113 P: 0.115). Durations of the first active disease period were longer in the polyphasic / persistent group (OR:1.275, P: 0.01). Active disease duration cut-off values of 1.5 months with sensitivity 85.7%, specificity 52.4% were observed on receiver operating characteristic curve analysis. The presence of hepatosplenomegaly at first flare was detected as an independent risk factor of polyphasic/persistent disease by multivariate analysis included both dosage and duration of a steroid (hazard ratio (HR): 4.129, P: 0.034), (HR: 3.992, P: 0.038). Multivariate recurrent events survival analysis determined ALT levels as a risk factor affecting polyphasic / persistent disease (HR: 0.986, P: 0.037). CONCLUSIONS: Glucocorticoid dose and duration did not affect the active disease periods and disease course in SJIA. An active disease period longer than 1.5 months, presentation of hepatosplenomegaly at the initial disease course, and high ALT levels at the recurrences should warn physicians of polyphasic / persistent disease.

The Possible Relationship Between Familial Mediterranean Fever and Chronic Nonbacterial Osteomyelitis: Coincidence or Coexistence?

BACKGROUND/OBJECTIVES: Chronic nonbacterial osteomyelitis (CNO) is an inflammatory disease characterized by recurrent attacks and remissions due to sterile bone inflammation. The CNO may be accompanied by various inflammatory diseases. The aims of our study were to determine the clinical, laboratory, and radiological characteristics of children with CNO, and to investigate the possible effect of concomitant diseases on the course of CNO. METHODS: Twenty-three patients who were diagnosed with CNO between 2012 and 2019 were analyzed. Demographic characteristics, clinical courses, laboratory and imaging findings, and concomitant diseases were recorded. The characteristics of the CNO patients with and without concomitant diseases were compared. RESULTS: The mean ± SD age of patients at the time of diagnosis and the last follow-up was 10.46 ± 4.1 and 12.47 ± 4.47 years, respectively. The median (range) time interval between disease onset and diagnosis was 5.33 (1-55) months. The mean ± SD duration of disease was 24.71 ± 16.76 months. Twelve patients (52.2%) were male. The most commonly affected areas were femur (74%), tibia/fibula (74%), and pelvis (52.2%). Age at symptom onset, age at diagnosis, mean number of lesions, presence of sacroiliitis, acute phase reactants at the start of disease, clinical and radiological remission rates, and treatment responses were not significantly different between the 13 patients with concomitant diseases and those without. Eight patients (34.8%) had familial Mediterranean fever (FMF), and all of them had exon 10 mutations. Four patients (17.4%) had juvenile spondylarthritis, one had inflammatory bowel disease, and one had psoriatic arthritis as concomitant diseases. Clinical remission was achieved in 19 patients (82.6%) and complete remission in 11 patients (47.8%) at the time of follow-up. CONCLUSIONS: In our cohort, half of the patients with CNO had concomitant diseases, with FMF being the most common. We think that the coexistence of FMF and CNO is not a coincidental one and that both may result due to an abnormality of a common pathogenetic pathway.

The Performances of the ACR 1997, SLICC 2012, and EULAR/ACR 2019 Classification Criteria in Pediatric Systemic Lupus Erythematosus.

OBJECTIVE: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease. The American College of Rheumatology (ACR) 1997, Systemic Lupus International Collaborating Clinics (SLICC) 2012, and European League Against Rheumatism (EULAR)/ACR 2019 SLE classification criteria are formed based on data mainly from adult patients. We aimed to test the performances of the SLE classification criteria among pediatric patients with SLE. METHODS: Pediatric patients with SLE (n = 262; 80.9% female) were included from 3 different centers in Turkey. As controls, 174 children (60.9% female) with other diseases who had ANA (antinuclear antibody) test results were included. The gold standard for SLE diagnosis was expert opinion. RESULTS: The sensitivities of the ACR 1997, SLICC 2012, and EULAR/ACR 2019 criteria were 68.7%, 95.4%, and 91.6%, respectively. The specificities of the ACR 1997, SLICC 2012, and EULAR/ACR 2019 criteria were 94.8%, 89.7%, and 88.5%, respectively. Eighteen patients with SLE met the SLICC 2012 but not the EULAR/ACR 2019 criteria. Among these, hematologic involvement was prominent (n = 13; 72.2%). Eight patients with SLE fulfilled the EULAR/ACR 2019 but not the SLICC 2012 criteria. Among these, joint involvement was prominent (n = 6; 75%). CONCLUSION: To our knowledge, this is the largest cohort study of pediatric SLE to test the performances of all 3 classification criteria. The SLICC 2012 criteria yielded the best sensitivity, whereas the ACR 1997 criteria had the best specificity. SLICC 2012 criteria performed better than EULAR/ACR 2019 criteria. Separation of different hematological manifestations in the SLICC 2012 criteria might have contributed to the higher performance of this criteria set.

Evaluation of familial Mediterranean fever patients concomitant with juvenile spondyloarthropathy.

OBJECTIVES: Familial Mediterranean fever (FMF) may present with various concomitant diseases. This study aims to evaluate the clinical characteristics of patients with FMF with Juvenile Spondyloarthropathy (jSpA). METHOD: Thirty-two patients diagnosed with FMF/jSpA, sixty-four with FMF, and fifty-four with jSpA were included in this retrospective study. Three patient groups were compared in terms of clinical and laboratory features. RESULTS: The mean ages of patients in the FMF/jSpA, FMF and jSpA groups were 15.75(11.50-19.83), 15,41(6.83-21.50), and 16(9-22) years, respectively. Chronic arthritis (OR: 0.11, p = .049), erythrocyte sedimentation rate values (OR:1.07, p = .011), and C-reactive protein values (OR:1,08, p: .039) of the patients in remission period were found higher, the international severity scores for FMF (ISSF) before and after colchicine treatment (OR: 1.16, p: .021, OR: 2,21, p: .012) were higher in the FMF/jSpA group compared to FMF. Plantar fasciitis was more common and HLA-B27 positivity rate was lower in the FMF/jSpA group (OR:0.08, p = .024), (OR:4.71, p = .002) compared to jSpA. FMF/jSpA patients were divided as previous diagnosed FMF and jSpA.The diagnosis of jSpA was at a younger age(p = .002), Juvenile arthritis damage index-articular(p = 0.022) and extraarticular(p = .026), and the rate of biologic drug usage(p = .015) were higher in the previous jSpA group. The number of FMF attacks before colchicine was lower in the previous jSpA group(p = .02). CONCLUSION: Our findings suggest that both classical FMF and jSpA findings were lower in patients with FMF/jSpA. Patients who were diagnosed with jSpA at an early age and who had enthesitis and plantar fasciitis should also be evaluated in terms of FMF.

Evaluation of the thicknesses of cartilage and enthesis in familial Mediterranean fever and enthesitis-related arthritis.

OBJECTIVE: Subclinical inflammation is still a controversial issue in inflammatory diseases. There is no reliable, easy, and cheap inflammation marker in daily clinical practices currently. This study aims to predict clinical remission using cartilage and tendon thicknesses. METHODS: Eleven patients with Familial Mediterranean Fever (FMF) who had musculoskeletal involvement before and 11 patients with Enthesitis-Related Arthritis (ERA) were included in this study. They were on remission with clinical and laboratory evaluations for at least three months. Demographic and clinical features of the subjects, including age, sex, body mass index, disease duration, age at onset, medical treatment, and laboratory evaluations, were all noted. Healthy children of the same age were included as the control group. The thicknesses of the bilateral knee, second metacarpophalangeal and ankle joints cartilages, quadriceps, superior and inferior patellar, and the Achilles tendons were measured with a linear probe. A total of 198 joint and 264 tendon thicknesses were measured. RESULTS: The thicknesses of metacarpophalangeal, knee, and ankle cartilages were higher in the FMF group than in the others. In the FMF group, the quadriceps tendon thickness was higher than in the ERA group, and the superior patellar tendon thickness was higher than in the control group (p<0.05). CONCLUSION: According to our preliminary findings, an increased thickness of the cartilage and tendon in FMF patients may be an indicator of subclinical inflammation. Increased thickness of the enthesis in FMF patients may also indicate that enthesitis-related arthritis will also develop in the future.

Blau Syndrome and Early-Onset Sarcoidosis: A Six Case Series and Review of the Literature.

OBJECTIVES: This study aims to discuss the clinical, laboratory and genetic findings, and treatment options for six patients who were diagnosed with Blau syndrome (BS)/early-onset sarcoidosis (EOS). PATIENTS AND METHODS: The study included four patients (2 males,2 females; mean age 7 years; range 4 to 10 years) with EOS and two siblings (1 male, 1 female; mean age 10 years; range, 9 to 11 years) with BS. Age, age of initial symptoms, age of diagnosis; articular involvement, presence of uveitis, dermatitis, or fever, other organ involvement, laboratory findings, results of metabolic tests for mucopolysaccharidosis and mucolipidosis, results of genetic, pathologic, and immunologic tests, radiologic findings to evaluate skeletal dysplasia, and treatment options were collected. RESULTS: The median age at diagnosis of all patients was 6 years (range, 1 to 10 years). Five patients had camptodactyly and bilateral boggy synovitis in the wrists and ankles, one had granulomatous inflammatory changes in the liver and kidney biopsy, and one had attacks of fever and granulomatous dermatitis. None had uveitis. The detected mutations in nucleotide-binding oligomerization domain containing 2 (NOD2) were P268S (rs2066842), M513T (rs104895473), R702W (rs2066844), V955I (rs5743291), H343Y (rs199858111), and M491L (16:50745293). The treatments of patients included corticosteroids, non-steroid anti-inflammatory drugs, methotrexate, infliximab, adalimumab, anakinra, and canacinumab. CONCLUSION: Camptodactyly and boggy synovitis are important signs of BS/EOS. Methotrexate and tumor necrosis factor blockers are more effective in patients with predominantly articular symptoms. In patients 5 and 6 and their mother, we determined a novel M491L mutation in the NOD2 gene. Currently, this work is in progress towards identifying the pathogenesis and treatment options for this disease.

Epidermolysis bullosa complicated with nephrotic syndrome due to AA amyloidosis: A case report and brief review of literature.

Epidermolysis bullosa (EB) encompasses a clinically and genetically heterogeneous group of rare inherited diseases characterized by marked mechanical fragility of epithelial tissues with blistering and erosions following minor trauma. Amyloidosis is one of the most important complications of EB mostly seen in recessive dystrophic EB (RDEB) patients and can involve the kidney, bowel, liver, and also respiratory system. Herein, we present a child, who is probably the youngest case of genetically diagnosed RDEB, complicated with amyloidosis reported in literature. A 6-year-old boy who was diagnosed with EB was referred to our center with nephrotic-range proteinuria and hypoalbuminemia. He had homozygous mutation in COL7A1 gene. Kidney biopsy was remarkable for amyloidosis with positive Congo red staining, and amyloid fibrils were seen on electron microscopy. Although he did not have any symptoms of autoimmune diseases and mutation in the MEFV gene, he was given colchicine because of positive family history for familial Mediterranean fever and amyloidosis.

Elemental mercury intoxication in 7 patients admitted to a pediatric rheumatology clinic.

Paç Kisaarslan A, Sözeri B, Bastug F, Gündüz Z, Yel S, Nalçacioglu H, Sahin N, Özdemir Çiçek S, Poyrazoglu H, Düsünsel R. Elemental mercury intoxication in 7 patients admitted to a pediatric rheumatology clinic. Turk J Pediatr 2019; 61: 786-790. Mercury (Hg) is a toxic heavy metal that can be classified into three groups; organic (methyl), inorganic (mercuric), and elemental (metallic) mercury(Hg0). Mercury intoxication occurs mostly with the elemental form which can potentially damage the function of any organ, or any subcellular structure. The target organ of mercury is the brain, but peripheral nerve function, renal function, immune function, endocrine and muscle function, and several types of dermatitis have been described. We present 7 patients admitted to a pediatric rheumatology clinic with severe extremity pain. One of the patients had acrodynia, two of them had hypertension, two of them had tubulopathy, and three of them had neuropathy. The treatments were Dimercaptosuccinic acid and metalcaptase. In this report, we emphasize that mercury intoxication should be kept in mind with unexplained extremity pain. Timely diagnosis and treatment may prevent severe morbidity and mortality.