Systemic juvenile idiopathic arthritis (sJIA, formerly called Still's disease or systemic juvenile rheumatoid arthritis) is officially a subset of JIA that describes patients with intermittent fever, rash, and arthritis. However, sJIA is probably an autoinflammatory disorder rather than an autoimmune disorder like other categories of JIA. (See 'Introduction' above and 'Overview' above.)
●sJIA can be difficult to diagnose because there are no specific diagnostic tests, and arthritis, which is necessary for definite diagnosis, is often not evident early in the course of the disease. In addition, infection and malignancies must be considered prior to the diagnosis of sJIA in these cases because patients can initially appear quite ill with high, spiking fever; rash; and often have hepatosplenomegaly or lymphadenopathy and elevated white blood cell (WBC) counts prior to the presentation of arthritis. (See 'Overview' above and 'Clinical manifestations' above and 'Laboratory findings' above and 'Diagnosis' above and 'Differential diagnosis'above.)
●The diagnosis is made clinically and is based upon the presence of intermittent, daily, high, spiking fevers (in a quotidian fever pattern) for at least two weeks and arthritis. A salmon-pink rash is also suggestive of the diagnosis, particularly when other clinical features are present. There are no laboratory findings that are specific for the diagnosis of sJIA, but granulocyte predominant leukocytosis, elevated acute-phase reactants including thrombocytosis, and hyperferritinemia should raise suspicion for this disorder in association with the other typical clinical features. (See 'Diagnosis' above and 'Laboratory findings' above and 'Clinical manifestations' above.)
●The differential diagnosis includes arthritis associated with infections, other autoimmune and autoinflammatory disorders, malignancy, and malaria. (See 'Differential diagnosis' above.)
Features of three of the major subtypes of juvenile idiopathic arthritis (JIA)
| Systemic JIA | Oligoarticular JIA | Polyarticular JIA | |
| Percent of JIA patients | 10 to 15 | 50 | 30 to 40 |
| Sex | F = M | F>M | F>M |
| Age | Any <17 years | Peak 2 to 3 years, rare >10 | Peaks 2 to 5, 10 to 14 years |
| Joints | Any number and any joint | Large joints, but rarely hips | Any, usually symmetrical and rare to start in hips |
| Fever, rash, lymphadenopathy, hepatosplenomegaly | Yes | No | No |
| Uveitis | Rare | 20%, most common in patients who are ANA positive | Less frequently seen than in oligoarticular JIA |
| Laboratory abnormalities | |||
| - Leukocytosis | Marked | No | No |
| - Anemia | Marked | No | Mild |
| - Elevated ESR | Marked | Mild | Mild |
| - ANA | Absent | Low titer common | Low titer common in younger |
| - Rheumatoid factor | Rare | Absent | 10 to 20% in those >10 years |
| - Elevated ferritin | Marked | No | Mild |
| Destructive arthritis | >50% | Rare | >50% |
| Response to methotrexate | Poor to moderate | Excellent | Excellent |
| Response to biologic drugs |
Poor to TNF inhibitors
Excellent to IL-1 and IL-6 inhibitors |
Excellent to TNF inhibitors and IL-6 inhibitors (although not commonly used)
Poor to IL-1 inhibitors |
Excellent to TNF inhibitors and IL-6 inhibitors
Poor to IL-1 inhibitors |
F: female; M: male; ANA: antinuclear antibody; ESR: erythrocyte-sedimentation rate; TNF: tumor necrosis factor; IL: interleukin.
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Cervical spine fusion in systemic juvenile idiopathic arthritis
Fusion of the cervical spine may affect up to 50% of children with systemic juvenile idiopathic arthritis in the first decade of life. Apophyseal joint space narrowing and bony ankylosis occur, especially at C2-C3. These changes are not usually present elsewhere in the spine.
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Systemic juvenile idiopathic arthritis rash
A salmon-pink rash is characteristic of this juvenile idiopathic arthritis (JIA) subtype. The rash is brought out by heat and often can be found in the axillae and around the waist, but may be present anywhere on the body.
Courtesy of Robert Sundel, MD.
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Systemic juvenile idiopathic arthritis rash with Koebner phenomenon
Systemic juvenile idiopathic arthritis rash on a patient's back is shown in Panel A, with a close-up view in Panel B. The rash usually consists of multiple round to oval, salmon-pink macules that are slightly raised and are of differing sizes. The rash can appear following stroking of the skin or other minor trauma (Koebner phenomenon).
Courtesy of Yukiko Kimura, MD.
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It will be clear to any clinician who sees a significant number of children that the nomenclature for juvenile arthritis is not yet complete and that many distinct diseases have been lumped together. There are children who do not fit into any category or who overlap more than one category. The new nomenclature should therefore be regarded as a "work in progress." Over time, this nomenclature will be further refined to allow better characterization of patients. The inability to properly distinguish different causes of arthritis significantly impairs our ability to determine optimal therapy. With improving genetic and pathophysiologic understanding of arthritis, trials will contain increasingly homogeneous collections of children with biologically distinct illnesses. In the interim, it is important for clinicians to recognize that this nomenclature was not intended for broad clinical use and that consensus treatment recommendations applied to all children with juvenile idiopathic arthritis (JIA) cannot be relied upon.
When dealing with children who fail to fit neatly into any of the categories delineated above, we must be careful not to confuse either parents or caregivers. The inability to satisfactorily place the patient into one of these categories does not exclude the presence of arthritis or the ability to make a diagnosis. Rather, these children should be told that they have juvenile arthritis. It is not important that their illness does not fit neatly into any of the subtypes defined thus far. As noted above, it is important to have well-defined groups of patients for investigational trials, but to not produce unnecessary confusion for patients, parents, and clinicians.
Overall, it is important that every clinician recognize that childhood arthritis is not a homogeneous entity. Thus, there is no single best:
●Characteristic appearance
●Diagnostic criterion
●Treatment
●Uniform prognosis
Many of the publications describing the natural history of juvenile arthritis and the efficacy of therapeutic modalities are based on trials which included all children with juvenile arthritis. These manuscripts are of questionable scientific value, since it is clear that such a large and diverse group of children includes diseases with myriad causes, prognoses, and responses to therapy. Unfortunately, even manuscripts which carefully categorized children into groups based on previous juvenile rheumatoid arthritis (JRA) or juvenile chronic arthritis (JCA) criteria may not be directly applicable to children diagnosed according to the International League of Associations for Rheumatology (ILAR) system. Hopefully, as the pathophysiologic bases of subsets of juvenile arthritis are better understood, more precise classification of children with arthritis will be possible.
Features of three of the major subtypes of juvenile idiopathic arthritis (JIA)
| Systemic JIA | Oligoarticular JIA | Polyarticular JIA | |
| Percent of JIA patients | 10 to 15 | 50 | 30 to 40 |
| Sex | F = M | F>M | F>M |
| Age | Any <17 years | Peak 2 to 3 years, rare >10 | Peaks 2 to 5, 10 to 14 years |
| Joints | Any number and any joint | Large joints, but rarely hips | Any, usually symmetrical and rare to start in hips |
| Fever, rash, lymphadenopathy, hepatosplenomegaly | Yes | No | No |
| Uveitis | Rare | 20%, most common in patients who are ANA positive | Less frequently seen than in oligoarticular JIA |
| Laboratory abnormalities | |||
| - Leukocytosis | Marked | No | No |
| - Anemia | Marked | No | Mild |
| - Elevated ESR | Marked | Mild | Mild |
| - ANA | Absent | Low titer common | Low titer common in younger |
| - Rheumatoid factor | Rare | Absent | 10 to 20% in those >10 years |
| - Elevated ferritin | Marked | No | Mild |
| Destructive arthritis | >50% | Rare | >50% |
| Response to methotrexate | Poor to moderate | Excellent | Excellent |
| Response to biologic drugs |
Poor to TNF inhibitors
Excellent to IL-1 and IL-6 inhibitors |
Excellent to TNF inhibitors and IL-6 inhibitors (although not commonly used)
Poor to IL-1 inhibitors |
Excellent to TNF inhibitors and IL-6 inhibitors
Poor to IL-1 inhibitors |
F: female; M: male; ANA: antinuclear antibody; ESR: erythrocyte-sedimentation rate; TNF: tumor necrosis factor; IL: interleukin.
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Systemic juvenile idiopathic arthritis: Course, prognosis, and complications
The course of systemic juvenile idiopathic arthritis (JIA) is highly variable, although there are three typical patterns: monophasic, polycyclic, and persistent (chronic). (See 'Course' above.)
●Three patterns of chronic disease activity occur in systemic JIA (see 'Course' above):
•Systemic manifestations (ie, fever and rash), but little to no arthritis.
•Persistent systemic manifestations and progressive arthritis.
•Progressive destructive arthritis despite resolution of systemic manifestations.
●Morbidity and mortality from systemic JIA have decreased with improvements in therapy, but mortality is still high in patients with severe disease, especially those with chronic pulmonary or vascular complications. (See'Prognosis' above.)
●Macrophage activation syndrome (MAS), severe growth retardation, and osteoporosis are the most common complications of systemic JIA or its treatment. (See 'Complications' above.)
Polyarticular juvenile idiopathic arthritis: Clinical manifestations, diagnosis, and complications
●The age at onset of polyarticular juvenile idiopathic arthritis (JIA) has a bimodal distribution. The first peak in incidence is between the ages of two and five years, and the second peak is between 10 and 14 years. It is more common in females than males at all ages. (See 'Epidemiology' above.)
●The clinical presentation of polyarticular JIA is varied and tends to fall into patterns based upon the age of onset. In children less than 10 years of age, polyarticular JIA often begins similarly to oligoarticular disease, with one or two joints affected. The development of the disease is often indolent until an intercurrent infection precipitates a dramatic increase in symptoms. The disease then becomes relentlessly progressive, spreading to involve five or more joints during the first six months after disease onset. Joint involvement is typically symmetrical. Older children and adolescents usually have a relatively rapid onset of inflammation in multiple joints, including involvement of the many small joints of the hands and feet, within two to three months of disease onset. (See 'Clinical presentation' above.)
●There are no diagnostic laboratory findings for JIA. However, patients often have a positive antinuclear antibody (ANA) and an elevated erythrocyte sedimentation rate (ESR, ≥40 mm/hour), anemia (hemoglobin concentration ≤11 g/dL), and hypergammaglobulinemia may be present. Other autoantibodies are not usually seen in patients with polyarticular JIA. (See 'Laboratory findings' above.)
●The diagnosis is made in children with arthritis in more than four joints during the first six months of disease and in whom other causes of polyarthritis have been excluded. (See 'Diagnosis' above and 'Laboratory findings'above.)
●The differential diagnosis includes a number of illnesses that may be self-limited or chronic in nature, including other forms of JIA (eg, psoriatic, systemic, enthesitis related), reactive arthritis, early-onset rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), systemic vasculitis, sarcoidosis, inflammatory bowel disease (IBD), epiphyseal dysplasia, and minocycline-induced autoimmunity. (See 'Differential diagnosis' above.)
●Complications include debilitating arthritis, uveitis, and osteoporosis. These complications may require additional therapies. (See 'Complications' above.)
ACKNOWLEDGMENT — The editorial staff at UpToDate would like to acknowledge Thomas JA Lehman, MD, who contributed to an earlier version of this topic review.
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