Pediatric Rheumatology

Pediatric Arthritis

arthritis affects kids too (250,000 in U.S. alone)

Pediatric rheumatology deals with musculoskeletal disorders seen in children (birth through adolescence)

many considerations that do not exist for adults – e.g., local or general growth arrest

Arthritis – defined clinically: swelling, tenderness, limited motion, heat, no erythema

pediatric arthritis often has more subtle symptoms than adult – there is usually no joint pain

most common presenting complaint is stiffness (esp. in the morning or after a nap) that disappears with movement
often undiagnosed or misdiagnosed because joint problems are unrecognized by the patient and family

Juvenile Arthritis

also called juvenile rheumatoid arthritis or juvenile chronic arthritis

Definition – arthritis with onset under age 16 that persists for at least 6 weeks – other diseases must be excluded

Classification of Juvenile Arthritis – three broad categories defined primarily by clinical symptoms

diseases develop slowly, so classification must be made >6 months after onset – even then 7-8% will be misclassified

(1) Systemic Onset Juvenile Arthritis (Still’s Disease) – 15% of juvenile arthritis cases; arthritis not present at onset

patients can suffer from symptoms for years – remission can occur, but patients often relapse years later

spiking fever – from below normal to 105° F or greater once or twice per day – irritability during high fever

evanescent rash – present in 50% of cases – macular, vague, rarely pruritic – usu. occurs with fever spikes

leukocytosis and elevated ESR (sedimentation rate) – almost always occurs with this disease

hepatosplenomegaly, lymphadenopathy, anemia – requires bone marrow biopsy to exclude leukemia

pericarditis, effusions, serositis – systemic problems

arthritis – appears weeks, months, or years after initial symptoms – very severe arthritis, often crippling

(2) Polyarticular Juvenile Arthritis – affects more than four joints – can occur with or without Rheumatoid Factor (RF)

Type I (RF seronegative) – usu. symmetrical, appears at puberty, more benign than type II; often remits spontaneously

Type II (RF seropositive) – childhood manifestation of RA – pre-teen and teenage girls (always >6 years old)

symmetrical, erosive lesions with rheumatoid nodules (subcutaneously and on tendons)

(3) Pauciarticular Juvenile Arthritis – affecting less than four joints

Type I – associated with positive anti-nuclear antibody (50%), young females (<6 years old), short lasting (<2 years)

not as crippling as other arthritis – hips are usually spared; 75% of cases involve only 1 joint, 50% just the knee

chronic iritis – usually appears before joint problems, but can be as many as 39 years after

leads to blindness if not treated early – 16% blind in at least one eye even with best methods available
often asymptomatic, so requires slit lamp examination by ophthalmologist
patients that develop iritis are usually positive for ANA and HLA-DR5 and negative for HLA-DR1

Type II – associated with positive HLA-B27 (Caucasian) or HLA-B7 (African American), usually older (>10 years) males

debilitating, since it frequently involves spine and hips; onset is usually monoarticular in lower extremity
joint pattern is asymmetric, and spares the hands, wrists, and cervical spine
sometimes associated with bowel disease or psoriasis
can progress to juvenile ankylosing spondylitis without bony erosion

called SEA – seronegative (no RF), enthesitis (tenderness of tendon attachments), arthritis

strong family history can usually be established

Therapy for Juvenile Arthritis

Treatment should always include rest, and exercises such as physiotherapy (e.g., swimming)

Drug administration:

aspirin/salicylates – used only with high fever and systemic onset due to risk of Rye’s syndrome

NSAID – all produce GI symptoms (hemorrhage)

low dose oral steroids (prednisone) – "best and worst treatment" – usually completely ameliorates symptoms

horrible side effects – leaches Ca out of skeleton, also stops growth via hypothalamic pituitary inhibition
reserved for worst cases; intra-articular steroid injections work too

other drugs: anti-malarials (hydroxychloroquine), gold/D-penicilamine, methotrexate, sulfasalazine, minocycline, calcineurin inhibitors (immuran/cyclosporine), TNFa blockers (increases susceptibility to infection)

Kawasaki Disease

rare disease of infancy (<6 years)

Diagnosis – based on the presence of 5 out of 6 symptoms:

(1) fever – persistent (>5 days duration) and unresponsive – often the earliest symptom, almost always present

(2) rash – polymorphous followed by desquamation

(3) bilateral conjuctival hyperemia

(4) extremity changes – induration of hands and feet, erythema of palms and souls, desquamation of fingers and toes

(5) lesions of the oropharynx – including erythema and fissuring of the lips and "strawberry tongue"

(6) lymphadenopathy – usually in the cervical area
often many months are required before enough symptoms for diagnosis appear – treatment must begin sooner

Associated Conditions – include many vague symptoms

most severe: coronary aneurisms (rarely lethal) and myocardial infarction (1/3 without any symptoms at all)

patients must be monitored via 2-D echocardiogram

Kawasaki disease is the #1 cause of childhood myocardial infarction (<14 years old)

arthralgia or arthritis, aseptic (viral) meningitis, hydrops of gall bladder, diarrhea, otitis media, hepatic dysfunction, uveitis, various diseases of blood vessels

patients are usually extremely irritable

Laboratory Findings – leukocytosis, thrombocytosis, elevated liver enzymes, sterile pyuria, occasional CSF pleocytosis

Therapies – IV gamma globulin (many patients respond well to this); also high dose aspirin to prevent coronary thrombosis

Juvenile Dermatomyositis – rare inflammatory disease of muscle (not arthritis)

Characteristics – inflammation of muscle accompanied by perivascular invasion

proximal muscle weakness – also weakness of smooth muscle
skin changes – periorbital edema, heliotrope rash on eyelids, Botrin’s papules – like SLE but crosses nasolabial folds
abnormal capillary microscopy – visible beneath fingernails (not single line but dilated capillary loops)
vascular dysfunction leading to vasculitis of skin and gut and lung disease
sometimes leads to calcinosis, a serious complication; also linked to certain types of cancer

Treatment

steroids
anti-malarial agents (for rashes)
immunosuppressive/cytotoxic agents (methotrexate, azathioprine, cyclosporine, cyclophosphamide)

What Causes All These Diseases? – ongoing research

Since these clinical syndromes have common symptoms and physical findings, it is likely that they have a common cause

What is this cause? – four possibilities:

(1) Genetic – family associations demonstrate inheritance, but no particular gene has been isolated
(2) Environmental – probably not, although some areas are endemic – internet rumor about dust mites unsubstantiated
(3) Infectious – possibly, but all reports (e.g., Chlamydia pneumoniae as a cause for Kawasaki) are unsubstantiated
(4) Immunological – T cells are indeed activated, and diseased synoviocytes bind IL-2

however, although oligoclonal T-cells can be occasionally be isolated, correlation has not been established

An Alternative Hypothesis:

These diseases might all involve an exaggerated immune response to a self-protein that resembles an antigen (possibly an infectious superantigen) to which the patient was exposed

Evidence:

All these diseases involve:

excess TNFa

autoantibodies (such as ANA)

altered host immunity (T-cell/synovial cell activation, proliferation of IL-6 in systemic disease)

If an ongoing inflammatory process indeed does cause these diseases:

treatment for early disease should be very different than treatment for late disease
it may be possible to alter the course of the disease by restoring normal immune function