Differential diagnosis portfolio of a pediatric rheumatologist: eight cases, eight stories

There is no single diagnostic test for any rheumatic disease. The diagnosis of a rheumatic disease is made by the sum of the findings in history, physical examination, laboratory, and imaging tests. A differential diagnosis list in pediatric rheumatology is quite long and mainly includes malignant, infectious, and inherited metabolic disorders. We aim to present cases that were referred to a pediatric rheumatology outpatient clinic with provisional diagnosis of a rheumatic disease but finally diagnosed with a non-rheumatic disease in order to emphasize the importance of differential diagnoses. Eight cases were presented in this manuscript. Five cases were referred with the provisional diagnosis of juvenile idiopathic arthritis. Sarcoidosis, chronic non-bacterial osteomyelitis, and autoinflammatory disease were the provisional referral diagnoses in three patients. Definitive diagnoses of the patients were as follows: acute lymphoblastic leukemia (two cases), bilineage acute leukemia, Hodgkin lymphoma, brucellosis, mucolipidosis type III, anhidrotic ectodermal dysplasia, and Freiberg disease. In children presenting with rheumatic complaints malignant, infectious and inherited metabolic disorders should always be in the differential diagnosis list of a pediatric rheumatologist. Alternative diagnoses should always be considered even in patients with a rheumatic disease when the patient does not respond to treatment or follows an unusual clinical course

Corticosteroid-resistant anakinra-responsive protracted febrile myalgia syndrome as the first manifestation of familial Mediterranean fever

Familial Mediterranean fever (FMF) is the most common type of monogenic periodic fever syndromes and characterized by recurrent self-limited attacks of fever and polyserositis. Musculoskeletal signs and symptoms are not uncommon and manifested as arthritis and myalgia. Myalgia may be spontaneous or exercise-induced that mostly affects lower limbs and spontaneously resolves in 2-3 days. Protracted febrile myalgia syndrome (PFMS) is another form of rare and severe muscle involvement in FMF. PFMS affects all muscle groups and lasts for several weeks. Herein we present a pediatric case of PFMS that presented as the first manifestation of FMF, not responded to prednisolone at all but showed dramatic improvement with anakinra. Our case has a few distinctive points. She did not have a diagnosis of FMF and also she did not have any previous complaints compatible with FMF. Thus, PFMS was the first sign of FMF in this patient. Most of the cases of PFMS show dramatic response to corticosteroids, but our case did not respond at all to high-dose corticosteroids and anakinra resulted in rapid resolution of the symptoms. Protracted febrile myalgia syndrome may be the first manifestation of FMF. It should be suspected in cases with prolonged and unexplained fever, severe myalgia, and high acute phase reactants

Complete and sustained resolution of calcinosis universalis in a juvenile dermatomyositis case with mycophenolate mofetil

Juvenile dermatomyositis (JDM) is a rare, multisystemic, idiopathic vasculopathy mainly affecting the muscles and the skin. Gastrointestinal system, lungs, joints and heart may also be involved. Characteristic skin findings are heliotrope rash and Gottron papules but extensive skin involvement as large necrotic lesions are rarely reported. Calcinosis is one of the major issues in the long term. Delay in diagnosis, inadequate therapy at the initial phase, prolonged persistent disease activity are considered as major risk factors for the development of calcinosis. Treatment of calcinosis is also a major issue because no single treatment modality has been found to reproducibly stop or reverse calcification

An extreme entity in differential diagnosis of musculoskeletal involvement-fibrodysplasia ossificans progressiva: a case based review

Fibrodysplasia ossificans progressiva is one of the most devastating disorder of mankind characterized by progressive heterotopic ossification. Apart from hallux valgus, other symptoms start to develop in the first decade of life. The initial symptoms are tumefactive lesions on the back that gives an impression of benign or malignant tumoral lesion. It may cause restricted motion of the neck and shoulders and magnetic resonance imaging of the lesions may be reported as myositis or myofasciitis and these children may be referred to rheumatologists. Currently there is no definitive treatment of the disease but the most important issue in these patients is "primum non nocere", because any invasive procedure could potentially trigger a flare and heterotopic calcification. Herein, we present a young case of fibrodysplasia ossificans progressiva to remind the typical signs and symptoms of the disease to all clinicians caring for children

Two cases of periodic fever syndrome with coexistent mevalonate kinase and mediterranean fever gene mutations

The periodic fever syndromes are autoinflammatory diseases that present with recurrent fever, serositis and rash. Familial Mediterranean fever is the most common periodic fever syndrome and characterized by recurrent attacks of fever, arthritis, peritonitis, pleuritis that typically last 1-3 days. Hyperimmunoglobulinemia D syndrome is another example of periodic fever syndromes and patients have recurrent fever attacks for 3-7 days accompanied by abdominal pain, rash, vomiting, diarrhea, arthralgia, arthritis, aphthous ulcers, and cervical lymphadenopathy. In some cases the clinical picture of the patient does not fit to one autoinflammatory syndrome because of the digenic inheritance. This may cause to overlap or atypical clinical features or an unexpected response to treatment. Herein we report two cases of hyperimmunoglobulinemia D syndrome that also had MEFV gene mutations and familial Mediterranean fever phenotype

Two cases of periodic fever syndrome with coexistent mevalonate kinase and Mediterranean fever gene mutations

The periodic fever syndromes are autoinflammatory diseases that present with recurrent fever, serositis and rash. Familial Mediterranean fever is the most common periodic fever syndrome and characterized by recurrent attacks of fever, arthritis, peritonitis, pleuritis that typically last 1-3 days. Hyperimmunoglobulinemia D syndrome is another example of periodic fever syndromes and patients have recurrent fever attacks for 3-7 days accompanied by abdominal pain, rash, vomiting, diarrhea, arthralgia, arthritis, aphthous ulcers, and cervical lymphadenopathy. In some cases the clinical picture of the patient does not fit to one autoinflammatory syndrome because of the digenic inheritance. This may cause to overlap or atypical clinical features or an unexpected response to treatment. Herein we report two cases of hyperimmunoglobulinemia D syndrome that also had MEFV gene mutations and familial Mediterranean fever phenotype