Rheumatic Diseases in Children

Rheumatic diseases in childhood pose special challenges to the treating physician: in addition to control of active symptoms, prevention of irreversible damage, and surveillance and early detection of disease flares, improved outcomes require that normal physical and emotional development be fostered in the face
of serious and long-term illness. 
In addition to the pediatric rheumatologist, a team including nurse, social worker, physical therapist, and occupational therapist
is essential to provide support to the child and family.  With the prime
goal of achieving normal function
and growth while increasing survival,
a long-term focus is necessary.

Treatment of both inflammatory and noninflammatory rheumatic diseases
of childhood is discussed.  The inflammatory diseases include systemic lupus erythematosus (SLE), neonatal lupus (NLE), juvenile dermatomyositis (JDMS), Henoch-Schönlein prpura (HSP), Kawasaki syndrome (KS), polyarteritis nodosa (PAN), Wegener’s granulomatosis (WG), and limited scleroderma.  Noninflammatory conditions include reflex neurovascular dystrophy (RND) and fibromyalgia syndrome (FMS).



SLE is an autoimmune, multisystem disease characterized by inflammation of blood vessels and connective tissue with variable clinical manifestations and unpredictable course.  Rare in childhood, the disease incidence is estimated at 0.4 per 100,000 population. Although childhood lupus can start at any age up to 16 years, most children are 10 years or older at presentation, and onset under 4 years of age is very rare. As is the case in adults, childhood SLE is predominantly a female disease. However, more males are affected in childhood than in adult onset because of the increased incidence in prepubertal children (3:1 female-to-male ration, in comparison with 7:1 in postpubertal onset and 8:1 in adults). The disease is more prevalent and more severe in blacks, Hispanics, and Asians. Multiple etiologic factors involved are immunologic, environmental, hormonal, ethnic, and genetic. Cutting-edge research into the genetic factors involved in disease expression is paramount to the development of innovative therapies for SLE. Studies currently in progress in adults and in murine models confirm the importance of gene polymorphism at several loci, including the major histocompatibility complex (MHC), complement proteins, immunoglobulin receptors, cytokines, and yet unidentified sites. Similar studies to define the genetics of the disease in childhood are ongoing.

Clinical manifestations of SLE in children are similar to those in adults, and the same guidelines are used for dignosis.  However, very few children have mild disease manifesting primarily in the skin, whereas renal involvement occurs in two thirds and neuropsychiatric disease in 20% to 40%. If unresponsive to treatment or untreated, the disease can be fulminant, resulting in death within months from infection or organ failure.Poor survival is associated with male sex, nephritis seizures, and thrombocytopenia.Advances in supportive therapies, such as antibiotics and antihypertensive drugs, critical care and dialysis, and better means of identifying children at high risk of organ involvement or life-threatening complications, have improved the prognosis. Current survival rates of children with lupus are 93% at 5 years, 85% at 10 years, and 79% at 15 years 4. , therefore, the course of the disease and its ultimate prognosis may no longer be worse in children than in adults. 7  However, the prognosis for children with end-stage renal disease who are receiving dialysis has been shown to be worse. Similarly, the experience in some pediatric rheumatology centers, including ours, is that children have more severe organ system involvement than do adults, 4, 5 and few children with SLE achieve adequate disease control without the use of steroids. The episodic nature of the disease, with spontaneous exacerbations not always predictable before organ damage, and the effects of chronic illness and potentially toxic medications on emotional as well as physical growth and development make the treatment of lupus particularly challenging in children.

The goals of treatment are to control active inflammation, to prevent or resolve organ damage, to protect normal growth, and to improve quality of life and survival. Milder symptoms may be treated with non-steroidal anti-inflammatory drugs (NSAIDs) and anti-malarials. When disease manifestations are potentially damaging to organs, disabling, or life-threatening, corticosteroid and immunosuppressive therapies are used.  Specialized therapies, such as anticoagulation, intravenous immune globulin (IVIG), or psychotropic drugs, may be required to treat such features as thromboses, uncontrolled thrombocytopenia, and psychosis. It is essential to help the child and the family establish support s ystems and effective coping mechanisms.  A team approach, in which a designated physician (pediatric rheumatologist) and specialized allied health personnel monitor the child and family, is important in enhancing trust and communication. In our unit, patients and families are encouraged to participate in a support group. The team nurse or social worker provides school liaison. Education about the disease process and its therapy is begun at the first visit and continues throughout follow-up.

General Therapeutic Measures

Supportive measures include management of nutritional status, blood pressure, fluid and electrolyte balance, and superimposed infections. Easy fatigability, a common feature of active disease, may require adjustment of the child’s schedule to provide rest periods and adequate sleep at night. Although the school schedule and physical education program may need to be altered initially, return to normal school activities as soon as possible is encouraged. Practice of sun protection techniques is emphasized. Children are taught to use sunscreen and to avoid direct sun exposure. Daily application of sunscreen with a sun protection factor (SPF) of 15 or higher is recommended. Waterproof preparations are preferred for younger children.Reactions such as erythema or stinging can occur, so patients must establish a personal choice of product by trial and error. Sun-protective clothing items are also available.  For adolescents, makeup can applied over sunscreen or makeup that contains a sun-block may be used.

Lupus dermatitis, which occurs in more than two thirds of children at presentation, responds well to hydroxychloroquine (Plaquenil) or systemic steroids, which may be indicated for other disease manifestations.  Topical steroids for treatment of persistent rashes should be used cautiously, because prolonged use, particularly of the high-potency fluorinated products, can cause local skin atrophy or depigmentation. For facial lesions, we start with 1% hydrocortisone cream, increasing the strength to 2.5% or changing to 0.1% betamethasone (Valisone) as necessary. Nonfacial lesions may be treated with high-potency preparations such as 0.05% betamethasone dipropionate (Diprolene) or mon with active disease. If they are symptomatic, sucralfate suspension applied topically or local application of 0.1% triamcinolone acetonide (Kenalog in Orabase) every  2 to 3 hours may be helpful.  Severe mucositis is treated with systemic steroids.

Salicylates and Nonsteroidal Anti-inflammatory Drugs

Indications for the use of salicylates and NSAIDs include arthralgia, myalgia, and mild arthritis.  When disease symptoms are mild, children can be treated with NSAIDs, often in combination with an antimalarial agent (see later discussion).  Because the use of aspirin (ASA) in children is associated with increased risk of liver toxicity11 as well as other adverse effects, we favor use of NSAIDs over salicylates.  When NSAID therapy is indicated, our preference is to use ibuprofen (40 to 45 mg / kg/ day divided into three doses), or naproxen (Naprosyn; 15 to 20 mg/ kg/ day divided into two doses).NSAIDs inhibit the enzye cyclooxygenase (COX), of which two distict forms have been described: COX-1, which functions as a housekeeping enzyme in multiple tissues including gastric mucosa, kidne, and brain, and COX-2, which is active at sites of inflammation.  The anti-inflammatory action of NSAIDs is attributed to inhibition of COX-2; however, all NSAIDs inhibit COX-1 as well, thereby creating the potential for toxic effects.  By their inhibitory effect on both enzymes, NSAIDs may cause multiple adverse effects.  For similar reasons, Cox-2 inhibitors may not provide protection from renal or other NSAID associated side effects in pediatric SLE. 12, 13 COX-2 inhibitors have not yet been approved for pediatric use.