Interleukin 10 and Transforming Growth Factor Beta Polymorphisms as Risk Factors for Kawasaki Disease: A Case-Control Study and Meta-Analysis.

BACKGROUND: Alteration in serum expression of Transforming Growth Factor-beta (TGF-ß) and IL-10 have been suggested to play a role in the pathogenesis of Kawasaki Disease (KD). Inconsistent reports exist on the association of IL-10 polymorphisms with KD susceptibility and Coronary Artery Aneurysms (CAA). METHODS: A number of 110 paediatric patients with KD and 140 healthy individuals were recruited to investigate the frequency of Single Nucleotide Polymorphisms (SNPs) of TGF-ß C/T at codon 10 (rs1982073), C/G at codon 25 (rs1800471) and IL-10 A/G at -1082 (rs1800896), C/T at -819 (rs1800871) and A/C at -592 (rs1800872) and their respective genotype and haplotypes. A comprehensive search was performed in MEDLINE and SCOPUS using the keywords of interleukin 10, transforming growth factor beta, and Kawasaki disease. Moreover, previous studies investigating the TGF-ß and IL-10 polymorphisms in KD were evaluated. Review Manager Version 5.1 Software was used to perform meta-analysis. RESULTS: There was no significant association between allelic or genotypic variants in the mentioned polymorphisms in TGF-ß or IL-10 with KD or CAA. The only significant haplotypic variant was TC variant at codon 10, and 25 of TGF-ß polymorphisms were associated with higher risk of KD. Meta-analysis of a total number of 770 patients vs. 1471 healthy controls showed no difference in the frequency of any of the IL-10 genetic variants in KD patients, regardless of the presence of CAA. CONCLUSION: Polymorphisms of TGF-ß or IL-10 are not associated with additional risk for KD in Iranian population. IL-10 polymorphisms at -1082, -819 and -592 positions are not associated with KD, nor do they predict coronary artery aneurysm formation.

Prevalence of Family History of Autoimmune Disorders in Juvenile Systemic Lupus Erythematosus.

One of the causes of infants' hospitalizations is bronchiolitis, while different viral agents could be causative agents. As there is little information regarding the common agents of bronchiolitis in Iranian infants, we designed this study to determine which agents were responsible for hospitalization due to bronchiolitis among infants in an Iranian tertiary center. Two hundred and three infants with bronchiolitis who were hospitalized in Bahrami hospital were enrolled. Data regarding age, sex, duration of hospitalization, exposure to smoking, previous antibiotic usage and fever were collected for all enrolled cases. Throat sample by means of soap was collected and rapid test with immunochromatography (IC) test was performed. Rapid test was positive in 59 (29%) cases and three cases had concomitant infection with two viruses. The most common viral agent was RSV (Respiratory Syncytial Virus). Mean age was significantly lower in cases with RSV or RSV+ adenovirus infectious in comparison with other two groups (adenovirus or influenza only), while mean duration of hospitalization was significantly longer in RSV/RSV+ adenovirus group. RSV is the most common viral etiology of bronchiolitis in Iranian infants less than one year old, which is related with younger age and longer duration of hospitalization. Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease. Near 10% of affected children have a relative with SLE. Autoimmune diseases are more common in relatives of children with SLE. As there is no study regarding the prevalence of autoimmune disease in cases with pediatric SLE, we designed this study to evaluate the prevalence of autoimmune disease in children with SLE. In this cross sectional study, 50 children with SLE and 50 healthy children were enrolled. A structured questionnaire was used to collect data regarding the presence of autoimmune diseases in relatives. One thousand eight hundred and thirty two relatives were evaluated in the case group and 1699 in the control group. The number of relatives with autoimmune diseases was significantly higher in the case group (26 vs 10). The most common autoimmune diseases were lupus, followed by thyroid diseases among cases, and thyroid diseases and rheumatoid arthritis in controls. According to the results of this study, the prevalence of autoimmune disorders is more common in relatives of children with SLE than in those of controls.

The Farsi version of the Juvenile Arthritis Multidimensional Assessment Report (JAMAR).

The Juvenile Arthritis Multidimensional Assessment Report (JAMAR) is a new parent/patient reported outcome measure that enables a thorough assessment of the disease status in children with juvenile idiopathic arthritis (JIA). We report the results of the cross-cultural adaptation and validation of the parent and patient versions of the JAMAR in the Farsi language. The reading comprehension of the questionnaire was tested in 10 JIA parents and patients. Each participating centre was asked to collect demographic, clinical data and the JAMAR in 100 consecutive JIA patients or all consecutive patients seen in a 6-month period and to administer the JAMAR to 100 healthy children and their parents. The statistical validation phase explored descriptive statistics and the psychometric issues of the JAMAR: the three Likert assumptions, floor/ceiling effects, internal consistency, Cronbach's alpha, interscale correlations, test-retest reliability, and construct validity (convergent and discriminant validity). A total of 102 JIA patients (14.7% systemic JIA, 67.6% oligoarticular, 15.7% RF negative polyarthritis, 2.0% other categories) and 198 healthy children, were enrolled in three paediatric rheumatology centres. Notably, none of the enrolled JIA patients is affected with enthesitis-related arthritis or undifferentiated arthritis. The JAMAR components discriminated healthy subjects from JIA patients. All JAMAR components revealed satisfactory psychometric performances. In conclusion, the Farsi version of the JAMAR is a valid tool for the assessment of children with JIA and is suitable for use both in routine clinical practice and clinical research.

Pro-inflammatory cytokine single nucleotide polymorphisms in Kawasaki disease.

AIM: Kawasaki disease (KD) is a systemic vasculitis of children associated with cardiovascular sequelae. Proinflammatory cytokines play a major role in KD pathogenesis. However, their role is both influenced and modified by regulatory T-cells. IL-1 gene cluster, IL-6 and TNF-α polymorphisms have shown significant associations with some vasculitides. Herein we investigated their role in KD. METHODS: Fifty-five patients with KD who were randomly selected from referrals to the main pediatric hospital were enrolled in this case-control study. Single nucleotide polymorphisms (SNPs) of the following genes were assessed in patients and 140 healthy subjects as control group: IL-1α at -889 (rs1800587), IL-1ß at -511 (rs16944), IL-1ß at +3962 (rs1143634), IL-1R at Pst-I 1970 (rs2234650), IL-1RN/A at Mspa-I 11100 (rs315952), TNF-α at -308 (rs1800629), TNF-α at -238, IL-6 at -174 (rs1800795) and IL-6 at +565. RESULTS: Twenty-one percent of the control group had A allele at TNF-α -238 while only 8% of KD patients had A allele at this position (P = 0.003, OR [95%CI] = 0.32 [0.14-0.71]). Consistently, TNF-α genotype GG at -238 had significant association with KD (OR [95% CI] = 4.31 [1.79-10.73]). Most controls carried the CG genotype at IL-6 -174 (n = 93 [66.9%]) while GG genotype was the most common genotype (n = 27 [49%]) among patients. Carriers of the GG haplotype at TNF-α (-308, -238) were significantly more prevalent among the KD group. No association was found between IL-1 gene cluster, allelic or haplotypic variants and KD. CONCLUSION: TNF-α GG genotype at -238 and GG haplotype at positions -308 and -238 were associated with KD in an Iranian population.

Interleukin-4 cytokine single nucleotide polymorphisms in kawasaki disease: a case-control study and a review of knowledge.

AIM: Kawasaki disease (KD) is a systemic vasculitis of medium-sized arteries. High levels of interleukin 4 (IL-4) and the dominance of Th2 cytokines seem to be a key feature in the acute phase of KD. In this study, the role of IL-4 and IL-4R gene polymorphisms were investigated in Iranian children with KD. METHODS: Fifty-five patients with KD and 140 healthy subjects as a control group were enrolled in this study. Single nucleotide polymorphisms (SNPs) of IL-4 gene at positions -1098 (rs2243248), -590 (rs2243250) and -33 (rs2070874), as well as IL-4RA gene at position +1902 (rs180275) were assessed in patients and the control group. RESULTS: The C allele and CC genotype of IL-4 gene at position -590 and at position -33 had positive associations and the CT genotype at -590 was negatively associated with KD (odds ratio (95% CI) = 0.04 [0.01-0.09]). The haplotype TCC was more frequent among the patients, while the haplotypes TTT and TTC had a negative association with KD. CONCLUSION: IL-4 polymorphisms might be associated with KD in an Iranian population.

Systemic Amyloidosis in a Teenage Boy With Inflammatory Bowel Disease.

Systemic amyloidosis is a very rare complication of inflammatory bowel disease (IBD). The reported cases of secondary amyloidosis in children with IBD are much fewer than those reported in adults. Herein, a teenage boy with Crohn's disease is presented who developed nephrotic syndrome due to renal involvement secondary to amyloidosis, whereas the patient was under treatment with corticosteroid and 6-mercaptopurine. To our best knowledge, this is the first reported case of secondary amyloidosis in a teenage Iranian boy with Crohn's disease.

Association of interleukin-6 single nucleotide polymorphisms with juvenile idiopathic arthritis.

Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatic disease in children. Genetics and inflammatory elements seem to act as major underlying factors in its pathogenesis. The aim of this study is to identify the associations between interleukin-6 (IL-6) gene polymorphisms and individuals' vulnerability to JIA in a group of Iranian pediatric patients. Fifty-four patients with JIA were enrolled in this investigation and compared with 139 healthy individuals. Using polymerase chain reaction with sequence-specific primers, cytokine genotyping was performed. The allele and genotype frequencies of two single nucleotide polymorphisms (SNPs) within the IL-6 gene at -174 and +565 positions were assessed. A significant positive association was observed for IL -6 -174 G allele in the patient group (p = 0.02). Furthermore, a positive association was observed in patients with JIA for the GG genotype at the same position (p < 0.01), thus revealing a predisposing effect in JIA patients. On the other hand, a significant negative association was found for IL-6 -174 CG genotype (p < 0.01) in the case group. No significant difference was discovered in both the allelic and genotypic frequencies of IL-6 +565 position between patients and controls. Additionally, haplotype analysis divulged over representation of IL-6 GG haplotype in patient group (p < 0.01) as well as IL-6 CG haplotype in healthy controls (p < 0.01). Certain allele, genotype, and haplotype in IL-6 gene were over expressed in patients with JIA, which probably could render individuals more susceptible to this disease.

Changes of Platelet Indices in Juvenile Idiopathic Arthritis in Acute Phase and After Two Months Treatment.

BACKGROUND: Various indices have been raised as predictors of activity and severity of juvenile idiopathic arthritis. OBJECTIVES: This study was conducted to investigate the changes of platelet indices in acute phase and two months after treatment in these patients. PATIENTS AND METHODS: In a cohort study, platelet count, mean platelet volume (MPV), platelet distribution width (PDW), plateletcrit (PCT) were evaluated in children referred to children's medical center, Tehran due to juvenile idiopathic arthritis from March 2013 to March 2014 during the acute phase and two months after standard treatment. The statistical data were analyzed by SPSS 19 software, and the significance level was set as P < 0.05. RESULTS: In this study, 55 children (24 boys and 31 girls) with mean ± SD age of 7.50 ± 3.35 years were studied. The mean ± SD value of platelet count was 441872.7 ± 151836.9 in the acute phase and reached 395418.2 ± 119601.6 two months after treatment (P = 0.01). The mean ± SD PCT in the acute phase of various subtypes of the disease was 0.32 ± 0.11, which reached 0.29 ± 0.10 after treatment (P = 0.09). However, the PDW range in different subtypes of the disease reached 13.4 ± 8.0 from 13.9 ± 2.9 and MPV reached 8.7 ± 0.9 from 8.8 ± 1.1 after treatment, but they were not significantly different from the results in the acute phase (P = 0.5). CONCLUSIONS: Platelet count is one of the most remarkable indices in JIA. Evaluation of PCT can also help determine the severity of the inflammatory process in the follow-up and treatment process.

Polymorphisms of genes encoding interleukin-4 and its receptor in Iranian patients with juvenile idiopathic arthritis.

As cytokines, including interleukin-4 (IL-4), seem to have a pivotal role in the pathogenesis of juvenile idiopathic arthritis (JIA), this study is aimed at investigating of association of polymorphisms in IL-4 and IL-4 receptor α (IL-4RA) genes with susceptibility to JIA. A case-control study was conducted on 53 patients with JIA and 139 healthy unrelated controls. Single nucleotide polymorphisms of IL-4 gene at positions -1098, -590, and -33, as well as IL-4RA gene at position +1902 were genotyped using polymerase chain reaction with sequence-specific primers method and compared between patients and healthy individuals. At the allelic level, C allele at IL-4 -33 was found to be more frequent in patients compared to control (P value <0.01). At the genotypic level, CC genotype at IL-4 -590 (P value <0.01), together with CC and TT genotypes at IL-4 -33 (P value <0.01), were significantly higher in patients with JIA, while TC genotypes at IL-4 -590 and -33 positions were found to be lower in case group (P value <0.01). At the haplotypic level, IL-4 (positions -1098, -509, -33) TTC, GCC, and TTT haplotypes were significantly lower than controls (P value <0.01, P value = 0.03, and P value = 0.04, respectively). Although, TCC haplotype at the same positions was found to be higher in patients (P value <0.01). Polymorphic site of +1902 IL-4RA gene did not differ between cases and controls. Polymorphisms in promoter region of IL-4 but not IL-4RA genes confer susceptibility to JIA and may predispose individuals to adaptive immune responses.

Penile Skin Involvement as the First Presentation of Henoch-Schonlein Purpura Report of Nine Cases and Review of Literature.

INTRODUCTION: Involvement of penis is a rare presentation in henoch-schonlein purpura (HSP). The presentations are mainly due to the deposition of immunoglobulin A (IgA) into the vessel walls. In this report, we present the clinical history of nine HSP cases that presented with penile skin involvement. CASE PRESENTATION: All patients were referred in the acute phase of HSP. Penile skin involvement was evident as erythema, edema, ecchymosis, or induration of prepuce and/or penile shaft, that appeared simultaneously with skin rash in seven patients. Gastrointestinal involvement was positive in six patients. Patients were treated with steroids and follow up visits were normal except for one patient that developed crescentic glomerulonephritis. CONCLUSIONS: We present nine cases of HSP with penile involvement in order to indicate another rare aspect of HSP and its possible complications as well as its appropriate treatment.

Dynamic Changes, Cut-Off Points, Sensitivity, and Specificity of Laboratory Data to Differentiate Macrophage Activation Syndrome from Active Disease.

PURPOSE: To compare the laboratory data and changes in these data between patients with MAS and patients with flare-up of the autoimmune diseases. METHODS: In a prospective study, the static laboratory data and dynamic changes in the selected data in 17 consecutive patients with MAS and 53 patients with active disease of SJIA, PJIA, Kawasaki disease, and SLE were compared. The ROC curve analysis was used to evaluate cut-off points, sensitivity, and specificity of the static and dynamic laboratory data to differentiate between MAS and active disease. RESULTS: In the MAS group, the mean CRP3, ALT, AST, total bilirubin, ferritin, LDH, PT, PTT, and INR were significantly higher and the mean WBC2, PMN2, Lymph2, Hgb1, 2, 3, ESR2, serum albumin, and sodium were significantly lower than in control group. Some of the important cut-off points were PLT2 < 209000/microliter, AST > 38.5, ALT > 38, WBC < 8200 × 103/UL, ferritin > 5277 ng/mL. CONCLUSION: The dynamic changes in some laboratory data, especially PLT, can differentiate between MAS and active disease. The changes in WBC, PMN, and ESR and the levels of the liver enzymes may also be helpful in the early differentiation. Very high levels of ferritin may also help the diagnosis along with other clinical and laboratory signs.

Tumor necrosis factor-alpha single nucleotide polymorphisms in juvenile systemic lupus erythematosus.

BACKGROUND: Juvenile systemic lupus erythematosus (JSLE) is a multi-system autoimmune disorder of unknown origin. Given the importance of the contribution of pro-inflammatory cytokines, including tumor necrosis factor-alpha (TNF-α), towards the pathogenesis of JSLE, this study was performed to assess TNFA gene polymorphisms in a case-control study. METHODS: Fifty nine patients with JSLE were enrolled in this study as case group and compared with healthy control subjects. The frequency of alleles, genotypes, and haplotypes of TNFA single-nucleotide polymorphisms (SNPs) at positions -308 and -238 were evaluated, using polymerase chain reaction with sequence-specific primers method. RESULTS: The G allele at position -238 in TNFA promoter region was significantly more frequent in patients with JSLE than in the healthy controls (P value<0.001), while the frequency of A allele at the same position was significantly lower than controls. Furthermore, a significant positive association for G/G genotype at the same position was detected in patients' group compared with control subjects (P value<0.001). The GA haplotype of TNFA (positions -308, -238) was significantly less frequent in case group than in controls (P value<0.001), while GG was the most frequent haplotype for TNFA in the patient group, compared to controls (P value<0.01). CONCLUSIONS: Pro-inflammatory cytokine gene polymorphisms may influence susceptibility to JSLE. Particular TNFA gene variants are associated with JSLE and could be used as a genetic marker for susceptibility to JSLE.

Lack of association between interleukin-10, transforming growth factor-beta gene polymorphisms and juvenile-onset systemic lupus erythematosus.

As abundant types of genetic predisposition and environmental factors seem to be associated with the development of juvenile-onset systemic lupus erythematosus (JSLE), we investigated the gene polymorphisms of two anti-inflammatory cytokines, including interleukin-10 (IL-10) and transforming growth factor-beta (TGF-ß), which were previously found to be associated with SLE in adults, in a group of patients with JSLE. We studied a group of 59 Iranian patients with JSLE in comparison with 140 healthy controls and assessed the frequency of alleles, genotypes, and haplotypes of IL-10 and TGF-ß single-nucleotide polymorphisms (SNPs) using polymerase chain reaction with sequence-specific primers method. The CA genotype was significantly more frequent at position -592 in IL-10 in patients with juvenile-onset systemic lupus erythematosus than in the controls (P = 0.01). Genotype CC was detected at the same position in 32.7 % of the patients; this frequency was significantly lower than the frequency of 50.7 % recorded in the healthy controls (P = 0.03). The TC haplotype of TGF-ß (codon 10, codon 25) was significantly more frequent in the patients with juvenile-onset systemic lupus erythematosus than in the healthy controls (P = 0.02). Nevertheless, these significant associations disappear after Bonferroni correction. Our findings suggest that IL-10 (-1082, -819, -592) and TGF-ß (codon 10, codon 25) gene variants may not be associated with the development of JSLE in Iranian population.

Periodic Fever and Neutrophilic Dermatosis: Is It Sweet's Syndrome?

A 7-year-old boy with high grade fever (39°C) and warm, erythematous, and indurated plaque above the left knee was referred. According to the previous records of this patient, these indurated plaques had been changed toward abscesses formation and then spontaneous drainage had occurred after about 6 to 7 days, and finally these lesions healed with scars. In multiple previous admissions, high grade fever, leukocytosis, and a noticeable increase in erythrocyte sedimentation rate and C-reactive protein were noted. After that, until 7th year of age, he had shoulder, gluteal, splenic, kidney, and left thigh lesions and pneumonia. The methylprednisolone pulse (30 mg/kg) was initiated with the diagnosis of Sweet's syndrome. After about 10-14 days, almost all of the laboratory data regressed to nearly normal limits. After about 5 months, he was admitted again with tachypnea and high grade fever and leukocytosis. After infusion of one methylprednisolone pulse, the fever and tachypnea resolved rapidly in about 24 hours. In this admission, colchicine (1 mg/kg) was added to the oral prednisolone after discharge. In the periodic fever and neutrophilic dermatosis, the rheumatologist should search for sterile abscesses in other organs.

Interleukin-6, interleukin-1 gene cluster and interleukin-1 receptor polymorphisms in Iranian patients with juvenile systemic lupus erythematosus.

BACKGROUND: Juvenile systemic lupus erythematosus (JSLE) is a polygenic, autoimmune disorder of unknown origin. As proinflammatory cytokines, including interleukin-6 (IL-6) and the interleukin-1 (IL-1) family, seem to contribute to the pathogenesis of JSLE, this investigation was performed to assess the associations of particular single nucleotide polymorphisms (SNPs) of IL-6 and IL-1 genes in a case-control study. METHODS: Fifty nine JSLE cases were recruited for this study as the patient group, and were compared against 140 healthy, unrelated, control subjects. Using the polymerase chain reaction with the sequence-specific primer method, genotyping was carried out for the IL-6 gene at positions -174 and nt565, as well as the IL-1α gene at position -889, the IL-1ß gene at positions -511 and +3962, the interleukin-1 receptor (IL-1R) gene at position Pst-I 1970, and the interleukin-1 receptor antagonist (IL-1Ra) gene at position Mspa-I 11100. RESULTS: RESULTS of the analyzed data revealed a remarkable, positive association for the promoter sequence of the IL-1ß gene at position -511 for T/T in the patient group compared with healthy controls (P value, 0.03). Furthermore, a significant negative association was found between the T/C genotype at the same position on the IL-1ß gene in juvenile SLE (P value, 0.03). CONCLUSIONS: cytokine gene polymorphisms might play a role in the pathophysiology of JSLE. Particular IL-1 gene variants could affect individual susceptibility to JSLE.

Morbidity and Mortality in Iranian Children with Juvenile Systemic Lupus erythematosus.

OBJECTIVE: Juvenile systemic lupus erythematosus (JSLE) is a common rheumatologic disorder that involves multi organ systems. Prognosis of lupus in children may be poorer than in adults. In this study, we determined mortality and morbidity rates in the pediatric SLE in Iran. METHODS: In a cross sectional study, we evaluated 120 children with SLE who had registered in our pediatric rheumatology database within 2004-2010. Data including sex, age, remission, age at the time of diagnosis, age at the time of study, various types of organ involvement, mortality and remission were extracted from this database. Findings : From 120 cases, 77% (92 cases) were females and 23% (28 cases) males (F:M=3.3). Mean follow up period was 56±32 months and mean age at the time of manifesting disease 10.34±2.9 years. Mortality rate was 10% (12 cases) in our investigation. Musculoskeletal involvement showed significant difference between various age groups (P<0.01), that was more frequent in group of 7 years and older. Frequency of oral ulcer and ophthalmic involvement in boys was significantly higher than in girls (P<0.05). Frequency of cardiovascular involvement (P<0.01) and renal involvement (P<0.01) was significantly higher in the patients who had no remission. There was a significant association between mortality rate and cardiac (P<0.02, OR=4.9), pulmonary (P<0.01, OR=10.167) and liver (P<0.05, OR=1.19) involvement. CONCLUSION: In our investigation 1-year survival rate was 97% and 5-year survival rate 89%. Liver, cardiac and pulmonary involvements have an association with higher mortality in JSLE patients.

Neonatal Lupus erythematosus Following Rheumatoid Arthritis: Case Report and Literature Review.

BACKGROUND: Neonatal lupus erythematosus (NLE) is a transient autoimmune disease of developing fetus and neonate in mothers with systemic lupus erythematosus (SLE). In this report we introduce an infant with NLE whose mother had rheumatoid arthritis. CASE PRESENTATION: Our case was a 40 day old male infant with discoid-like and annular skin lesions over forehead and neck, irritability and low grade fever. There was a history of prematurity due to preeclampsia. There was no cytopenia or cardiac involvement but liver enzymes were more than 5-fold increased. FANA, Anti Ro and La were negative. The mother had a history of un-controlled rheumatoid arthritis for 12 years with deformity in metacarpal and PIP and ulnar deviation in hands. FANA=1/640 and anti-SSB/La was positive in the mother but there was no other clinical and paraclinical sign of SLE. Without any treatment and during months, the skin and mucosal lesions gradually disappeared without any scar and liver enzymes reached the normal level. After 6 months follow up, he was symptom free with normal growth and development. CONCLUSION: We recommend to check anti SSA/Ro and anti SSB/La antibodies in all pregnant women with connective tissue diseases to prevent life-threatening involvement of the infant.

Caseous granuloma: tuberculosis or chronic recurrent multifocal osteomyelitis?

BACKGROUND: Chronic recurrent multifocal osteomyelitis (CREMO) is one of the autoinflammatory bone disorders due to disturbance in innate immune system. Up to now, there is no reported case of caseous granulomas in the CREMO. We report a boy with sterile granolumatous osteomyelitis. CASE PRESENTATION: A four-year-old boy presented with swelling and pain in the left wrist, malaise and bilateral erythematous pustulosis on the palmar region which had resolved spontaneously after about 7 days. The histopathology of the lesions showed severe acute and chronic inflammatory process and chronic granulomatous reaction with caseating necrosis (granulomatous osteomyelitis). The direct smear, culture and PCR for the mycobacterium tuberculosis and atypical mycobacteria were negative. About five months after initiation of the anti-mycobacterial treatment, he was referred to the rheumatology clinic with left elbow pain, effusion and decreased range of motion, and bilateral erythematous palmar pustulosis. He was diagnosed as CREMO based on two exacerbations, repeatedly negative cultures, and concomitant acute and chronic lesions in the histopathology and X-ray. Naproxen and pamidronate every 3 months were started and all other medications were stopped. Two months after the first dose of pamidronate, he became symptom-free and forearm X-ray showed disappearance of the osteolytic lesions and periosteal reactions. CONCLUSION: The diagnosis of CREMO should be considered in the patients with lytic bone lesions. In addition, the clinicians should be aware of the possibility of caseating granuloma in the cases with possible diagnosis of CREMO.

Periodic Fever: A Review on Clinical, Management and Guideline for Iranian Patients - Part II.

Periodic fever syndromes are a group of diseases characterized by episodes of fever with healthy intervals between febrile episodes. In the first part of this paper, we presented a guideline for approaching patients with periodic fever and reviewed two common disorders with periodic fever in Iranian patients including familial Mediterranean fever (FMF) and periodic fever syndromes except for periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA). In this part, we review other autoinflammatory disorders including hyper IgD, tumor necrosis factor receptor-associated periodic syndrome (TRAPS), cryopyrin associated periodic syndromes, autoinflammatory bone disorders and some other rare autoinflammatory disorders such as Sweet's and Blau syndromes. In cryopyrin associated periodic syndromes group, we discussed chronic infantile neurologic cutaneous and articular (CINCA) syndrome, Muckle-Wells syndrome and familial cold autoinflammatory syndrome. Autoinflammatory bone disorders are categorized to monogenic disorders such as pyogenic arthritis, pyoderma ;gangraenosum and acne (PAPA) syndrome, the deficiency of interleukine-1 receptor antagonist (DIRA) and Majeed syndrome and polygenic background or sporadic group such as chronic recurrent multifocal osteomyelitis (CRMO) or synovitis, acne, pustulosis, hyperostosis and osteitis (SAPHO) syndrome are classified in sporadic group. Other autoinflammatory syndromes are rare causes of periodic fever in Iranian system registry.