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Reactive Arthritis

Acknowledgment The authors and editors acknowledge the contributions of the authors of this chapter in the 7th edition of the Textbook of Pediatric Rheumatology, Drs. Rubén Burgos-Vargas and Janitzia Vázquez-Mellado. This chapter is dedicated to the memory of Elia Ayoub, MD. Reactive arthritis (ReA) is a term for a group of diverse inflammatory arthropathies in which the joint and extraarticular manifestations are caused by a preceding…

Lyme Disease

Lyme arthritis was first described in 1977 by Steere et al. in a cluster of children thought to have juvenile rheumatoid arthritis. They lived in and around Old Lyme, Connecticut. Subsequent studies documented that the disease was caused by the Ixodes tick-transmitted spirochete Borrelia burgdorferi , , and arthritis was one manifestation of a multisystem infection with cutaneous, neurological, cardiac, and musculoskeletal involvement. The disease is now…

Infectious Arthritis and Osteomyelitis

Musculoskeletal infections are a significant cause of morbidity and mortality in children worldwide, and their early diagnosis is often critical. Acute infections may present clinically as osteomyelitis, septic arthritis, osteomyelitis combined with septic arthritis, spondylodiscitis, or pyomyositis. Acute osteomyelitis is an inflammatory process in bone, usually the long bones of the lower and upper extremities, , accompanied by bone destruction. It is usually the result of…

Primary Immunodeficiencies and Rheumatic Diseases

Introduction Immunological derangements are recognized to play a significant role in the pathogenesis of rheumatic diseases in children, and primary immunodeficiency disorders (PIDDs) or inborn errors of immunity (IEIs) can occasionally be identified in children who have otherwise typical juvenile arthritis (JIA), systemic lupus erythematosus (SLE), or vasculitis. Moreover, many children referred to rheumatology services with a suspicion of inflammatory rheumatologic disorders present with a range…

Macrophage Activation Syndrome

Definition Macrophage activation syndrome (MAS) is a severe, potentially fatal complication of rheumatic diseases caused by excessive activation and expansion of macrophages and T cells, leading to an overwhelming inflammatory reaction. The main manifestations of MAS include fever, hepatosplenomegaly, lymphadenopathy, severe cytopenias, liver enzyme elevation, and coagulopathy consistent with disseminated intravascular coagulation (DIC). Striking hyperferritinemia is another characteristic laboratory finding. Numerous, well-differentiated macrophage phagocytosing hematopoietic elements…

Pediatric Sarcoidosis

Pediatric sarcoidosis encompasses a spectrum of childhood granulomatous inflammatory conditions, with the hallmark being the presence of noncaseating epithelioid giant cell granulomas in a variety of tissues and organ systems. The finding in 2001 of a mutation in the nucleotide-binding oligomerization domain 2/caspase activation recruitment domain 15 (NOD2/CARD15) gene among patients with a history of familial granulomatous arthritis constituted a major advance and revealed the complexity…

Autoinflammatory Bone Diseases

Autoinflammatory Bone Diseases Overview Autoinflammatory disorders (covered extensively in Chapter 39 ) result from aberrant and/or spontaneous activation of components of the innate immune system. , At least initially, they occur in the absence of high titer autoantibodies or autoreactive lymphocytes. This, by definition, distinguishes them from classic autoimmune disorders. , Autoantibodies and autoreactive lymphocytes, however, may develop over the course of disease partially as a…

Periodic Fever Syndromes and Other Inherited Autoinflammatory Diseases

Repeated febrile episodes lasting for a few days to a few weeks are common in young children. Infection is the most common etiological factor. However, after infectious causes and malignancy have been excluded, rheumatic illnesses enter the differential diagnosis. Unexplained bouts of fever with a characteristic frequency and constellation of symptoms fall under the term recurrent or periodic fever syndrome . Such disorders are defined as…

Behçet Disease

Introduction and Historical Review In 1937 the Turkish dermatologist Hulusi Behçet described the syndrome that bears his name, comprising the clinical triad of aphthous stomatitis, genital ulceration, and uveitis. Subsequently Adamantiades defined the thrombophlebitis and Matteson identified even earlier reports of this condition, including those from Japan. The history of Behçet disease (BD) has been reviewed by Kaklamani et al. Definitions and Classifications In the nomenclature of…

Takayasu Arteritis and Other Vasculitides

Takayasu Arteritis In 1908 the Japanese ophthalmologist Takayasu and his colleagues described the association of retinal vessel abnormalities with absent wrist pulses. Takayasu arteritis (TA) is a rare, chronic, relapsing granulomatous large-vessel vasculitis affecting the aorta, its major branches, and the pulmonary artery. Absence of the peripheral pulses has given it the name “pulseless disease.” Definition and Classification TA is classified under predominately large-vessel vasculitis in…

Antineutrophil Cytoplasmic Antibody Associated Vasculitis

Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a group of vasculitides characterized by small- to medium-sized blood vessel inflammation, clinically overlapping features, and the presence of ANCA. This group comprises granulomatosis with polyangiitis (GPA), formerly Wegener granulomatosis; microscopic polyangiitis (MPA); eosinophilic granulomatosis with polyangiitis (EGPA), formerly Churg–Strauss syndrome; and renal-limited pauci-immune glomerulonephritis. These conditions are rare in childhood and adolescence. Consequently, most knowledge about them comes…

Kawasaki Disease

Historical Background Kawasaki disease (KD) is one of the most common vasculitides of childhood. This vasculitis bears the name Kawasaki disease because of the highly detailed description of this illness in 50 children by Tomisaku Kawasaki in 1967. Scattered case reports of young children who died of ruptured or thrombosed coronary artery aneurysms have appeared in the medical literature since 1871. , A clinical syndrome comprising…

Polyarteritis Nodosa

Introduction Polyarteritis nodosa (PAN) was first described by Kussmaul and Maier in 1866. The original and subsequent descriptions identified the pathological features of necrotizing arteritis with nodules along the walls of medium and small muscular arteries, leading to thrombosis or aneurysm, affecting multiple organ systems throughout the body. Despite some overlap with smaller vessel disease, PAN is a distinct entity. Notably, the disease varies in its…

Immune Complex Small-Vessel Vasculitis: IgA Vasculitis (Henoch–Schönlein) and Hypersensitivity Vasculitis

Necrotizing vasculitis that affects small blood vessels (especially the postcapillary venules, capillaries, and arterioles) is often caused by immune complex deposition and may show leukocytoclastic vasculitis on histology ( Fig. 33.1 and Box 33.1 ). , The term leukocytoclasis refers to the infiltration of polymorphonuclear leukocytes into vessel walls, resulting in necrosis with scattered nuclear debris, and thus it is not a diagnosis in itself. This…

Vasculitis and Its Classification

The term vasculitis indicates the presence of inflammation in a blood vessel wall. The inflammatory infiltrate may be one that is predominantly neutrophilic, eosinophilic, or mononuclear. Perivasculitis describes inflammation around the blood vessel wall but without mural involvement. Vasculopathy, a broader term, indicates an abnormality of blood vessels that may be inflammatory or degenerative or may result from intimal proliferation. Vessel Structure and Function Blood vessels…

Inflammatory Central Nervous System Disorders

Acknowledgements The authors wish to express their gratitude to Drs. Adam Kirton and Susanne Benseler who authored the previously published version of this chapter. Approach to Inflammatory Brain Disorders Inflammatory disorders of the central nervous system encompass an array of acquired diseases characterized by relapsing or progressive clinical deficits and by neuroimaging features suggestive of focal inflammatory lesions. Lesions may involve the white matter predominantly (multiple…

Raynaud Phenomenon and Vasomotor Syndromes

Introduction Episodic color changes of the hands and feet in response to cold or stress, known as Raynaud phenomenon (RP), are a frequent complaint among patients presenting to pediatric rheumatology clinics. The first description of vasomotor instability triggered by cold exposure, or “local asphyxia of the extremities,” is ascribed to A.G. Maurice Raynaud, a French medical student whose name has become synonymous with this disorder. Despite…

Sjögren Syndrome and Immunoglobulin-G4 Disease

SjÖgren Syndrome The syndrome of chronic inflammation of the exocrine glands, principally the salivary and lacrimal glands, was first described by Henrik Sjögren, a Swedish ophthalmologist, who published in 1930 the first complete description of a disorder he named keratoconjunctivitis sicca. He reported that the disorder occurred most often in menopausal women and that arthritis was a prominent feature of the disease, as was a raised…

Localized Scleroderma and Eosinophilic Fasciitis

Scleroderma refers to hard skin that results from an excessive deposition of collagen. In the localized form (localized scleroderma [LS], also called morphea ), inflammation in the skin and subcutaneous tissues triggers the process of fibrosis. LS and the systemic form, systemic sclerosis (SSc), are chronic diseases that share some pathophysiological pathways but differ greatly in their clinical features and morbidities. LS is usually unilateral, less…

Juvenile Systemic Sclerosis

Introduction The scleroderma disorders in children encompass both systemic sclerosis (SSc) and localized scleroderma (LS), also termed morphea . Juvenile systemic sclerosis (JSSc) is much less common than juvenile localized scleroderma (JLS) and comprises less than 10% of all SSc cases. , Both share the general histopathologic features of an initial inflammatory state, followed by collagen deposition and atrophy of the skin and underlying connective tissue.…