Evaluation of childhood malignancies presenting with musculoskeletal manifestations from two different divisions: a multicenter study.

BACKGROUND: The aim of the study was to evaluate the approaches of pediatric rheumatologists and pediatric hematologists to patients with similar musculoskeletal (MSK) complaints and to highlight the differences that general pediatricians should consider when referring patients to these specialties. METHODS: This is a cross-sectional study involving the patients who applied to pediatric rheumatology centers with MSK complaints and were diagnosed with malignancy, as well as patients who were followed up in pediatric hematology centers with a malignancy diagnosis, and had MSK complaints at the time of admission. RESULTS: A total of 142 patients were enrolled in the study. Of these patients, 83 (58.4%) applied to pediatric rheumatology centers, and 59 (41.6%) applied to pediatric hematology centers. Acute lymphoblastic leukemia (ALL) was the most common diagnosis among the patients who applied to both centers, with 80 cases (56.3%). The median age of diagnosis was 87 (interquartile range, IQR: 48-140) months. The most common preliminary diagnosis in pediatric rheumatology centers was juvenile idiopathic arthritis (JIA), with 37 cases (44.5%). MSK involvement was mainly seen as arthralgia, and bone pain. While arthralgia (92.7%) was the most common complaint in rheumatology centers, bone pain (88.1%) was more common in hematology centers. The most frequently involved joints were the knee (62.9%), ankle (25.9%), hip (25%), and wrist (14%). The most common laboratory abnormalities were high lactate dehydrogenase (LDH), high C-reactive protein (CRP), anemia, and high erythrocyte sedimentation rate (ESR). Thrombocytopenia, neutropenia, and high LDH were statistically significantly more frequent in patients admitted to hematology centers than in patients admitted to rheumatology centers (p < 0.001, p=0.014, p=0.028, respectively). Patients who applied to rheumatology clinics were found to have statistically significantly higher CRP levels (p=0.032). CONCLUSIONS: Malignancies may present with only MSK system complaints in childhood. Therefore, malignancies should be included in the differential diagnosis of patients presenting with MSK complaints.

Inflammatory comorbidities in the largest pediatric Familial Mediterranean fever cohort: a multicenter retrospective study of Pediatric Rheumatology Academy (PeRA)-Research Group (RG).

AIM: The aim of this study was to investigate the frequency and type of FMF-associated inflammatory diseases in a large FMF pediatric patients and to compare them to those FMF patients without concomitant inflammatory diseases. MATERIALS AND METHODS: Familial Mediterranean fever patients enrolled in the Pediatric Rheumatology Academy (PeRA)-Research Group (RG) were included. The patients were divided into two groups according to concomitant inflammatory disease as FMF patients who had a concomitant inflammatory disease (group 1) and FMF patients who did not have a concomitant inflammatory disease (group 1). The clinical findings and treatments were compared between the two groups. RESULTS: The study group comprised 3475 patients with FMF. There were 294 patients (8.5%) in group 1 and 3181 patients (91.5%) in group 2. Juvenile idiopathic arthritis (n = 136) was the most common accompanying inflammatory disease. Arthritis, M694V homozygosity, and the need for biological therapy were more frequently observed in Group 1 (p < 0.05). Fever and abdominal pain were more frequently detected in Group 2 (p < 0.05). FMF patients with concomitant inflammatory diseas more frequently demonstrated colchicine resistance. There were no significant differences in the median attack frequency, chest pain, amyloidosis, erysipelas-like erythema, or family history of FMF between the two patient groups. CONCLUSION: To the best of our knowledge, this is the largest pediatric cohort reviewed to date. FMF patients may have different clinical profiles and colchicine responses if they have with concomitant inflammatory diseases. Key points • FMF is associated with some inflammatory comorbidities diseases. • To the best of our knowledge, this is the largest cohort evlauated pediatric FMF associated inflammatory comorbidities diseases reviewed to date.

A pediatric case of Takayasu's arteritis with anti-neutrophil cytoplasmic antibody-associated vasculitis triggered by COVID-19 infection.

Takayasu's arteritis (TA) is a rare chronic granulomatous vasculitis characterized by large-vessel involvement. The aorta and its main branches are most commonly involved. Although pulmonary artery involvement is common, hemoptysis or respiratory findings are rarely seen. Herein, we present a case of TA who developed anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis with diffuse alveolar hemorrhage after coronavirus disease 2019 (COVID-19) infection. A 17-year-old female patient with the diagnosis of TA presented with cough, bloody vomiting, and diarrhea. In follow-up, she developed tachypnea and dyspnea and was transferred to the pediatric intensive care unit. The findings on the chest computed tomography were compatible with acute COVID-19 infection, but the SARS-CoV2 reverse transcription-polymerase chain reaction test was negative, but SARS-CoV2 immunoglobulin (Ig) G and IgM antibody tests were positive. The patient was not vaccinated against COVID-19. The bronchoscopy showed bronchial mucosal fragility, bleeding foci, and mucosal bleeding. The broncoalveolar lavage hemosiderin-laden macrophages were seen in the histopathologic examination. The indirect immunofluorescence assay-ANCA test became 3 (+) with myeloperoxidase (MPO)-ANCA of 125 RU/ml (normal: <20). Cyclophosphamide and pulse steroid treatment were started. After immunosuppressive therapy, the patient condition improved and did not have hemoptysis again. The successful response was obtained by applying balloon angioplasty to the patient with bilateral renal artery stenosis. Types of post-COVID vasculitis include thromboembolic events, cutaneous vasculitis, Kawasaki-like vasculitis, myopericarditis, and ANCA-associated vasculitis. It is thought that COVID-19 may impair immune tolerance and trigger autoimmunity with cross-reaction. To the best of our knowledge, the third pediatric case was reported with MPO-ANCA-positive COVID-associated ANCA vasculitis.

Real-Life Data From the Largest Pediatric Familial Mediterranean Fever Cohort.

Familial Mediterranean fever (FMF) is the most common monogenic autoinflammatory disease manifesting phenotypic heterogeneity. It is a clinically diagnosed disease supported by MEditerranean FeVer (MEFV) gene mutation analysis. However, the phenotype-genotype correlation is not yet established clearly. We aimed to determine the clinical findings, phenotype-genotype correlation, and treatment outcomes within a large pediatric FMF cohort. The medical charts of children with FMF who were diagnosed and followed up at the eight pediatric rheumatology units were reviewed retrospectively. All patients in the cohort were analyzed for sequence variants in exon 2,3,5 and 10 of the MEFV gene. Patients without any mutations or with polymorphisms including R202Q were excluded. A total of 3,454 children were involved in the study. The mean ± standard deviation of current age, age at symptom onset, and age at diagnosis were 12.1 ± 5.2, 5.1 ± 3.8, and 7.3 ± 4.0 years, respectively. Of 3,454 patients, 88.2% had abdominal pain, 86.7% had fever, 27.7% had arthritis, 20.2% had chest pain, 23% had myalgia, and 13.1% had erysipelas-like erythema. The most common MEFV mutation patterns were homozygous (32.5%) and heterozygous (29.9%) mutations of exon 10. Homozygous M694V was present in 969 patients (28.1%). Allele frequencies of common mutations were M694V (55.3%), M680I (11.3%), V726A (7.6%), and E148Q (7.2%). Children carrying homozygous or compound heterozygous exon 10 mutations had an earlier age of disease onset (4.6 vs. 5.6 years, p = 0.000) and a higher number of attacks per year (11.1 vs. 9.6, p = 0.001). Although 8% of the patients had a family history of amyloidosis, 0.3% (n = 11) had the presence of amyloidosis. M694V homozygosity was detected in nine patients who developed amyloidosis. Colchicine resistance was present in 4.2% of our patients. In this largest pediatric cohort reviewed and presented to date, patients with exon 10 mutations, particularly the M694V homozygous mutation, have been demonstrated earlier disease onset, annual attack count, and more frequent colchicine-resistant cases. Although E148Q is considered as a polymorphism in some populations, it was identified as a disease-causing mutation in our cohort. Secondary amyloidosis is still happening in adults however, it is extremely rare among children, presumably due to increased awareness, tight control, and the availability of anti-IL1 agents in colchicine-resistant cases.

Eosinophilic granulomatosis with polyangiitis without respiratory symptoms or asthma in an adolescent: case report and literature review.

Eosinophilic granulomatosis with polyangiitis (EGPA), also known as Churg-Strauss syndrome, is a systemic necrotizing vasculitis of the small and medium vessels. It is primarily associated with respiratory conditions such as asthma and sinusitis as well as eosinophilia, neuropathy, pulmonary infiltrates, and vasculitis. EGPA is extremely rare in the pediatric age group, and respiratory system disorders are usually predominant in EGPA patients. A 14-year-old boy presented with rash and severe extremity pain. He had eosinophilia, and electroneuromyography demonstrated sensorimotor polyneuropathy. His skin biopsy revealed necrotizing eosinophilic vasculitis and eosinophilic panniculitis. Although he had no respiratory symptoms or history of asthma, prominent pulmonary involvement was evident on thoracic MRI. After treatment, his complaints of pain improved but mild neuropathy persisted. After 4 years of follow-up, he had minimal hypoesthesia in his right hand but had not experienced any relapses. This case highlights the fact that in cases suspected of EGPA, even without respiratory symptoms or asthma, detailed imaging should be performed for a definitive diagnosis. In addition, mild neurological findings may persist despite treatment in EGPA. The relevant literature on EGPA, with specific reference to pediatric cases, is reviewed.