Medication Summary
Therapeutic interventions for children with mixed connective tissue disease (MCTD) should occur under the direction or with the advice of an experienced physician. Various medications are used to treat individuals with mixed connective tissue disease and are chosen depending on disease manifestations. Goals of therapy are to control disease manifestations, allowing the child to have a good quality of life without major disease exacerbations, and to prevent serious organ damage that adversely affects function or life span. At the same time, the physician is challenged to prevent intolerable adverse effects from the therapeutic regimen.
Prior to treatment, identify diagnostic criteria and exclude other possible diagnoses. For those patients who do not have sufficient findings to fulfill diagnostic criteria, determine a course of action based on medical judgment and set time aside to answer all questions with the patient, family, and caregivers. Because they may be helpful, offer literature and support groups.
Many of these drugs have serious adverse effects, contraindications, and drug interactions. A high risk of infection, infertility, and future cardiovascular disease exists. Most medications are contraindicated during pregnancy. Advise patients with mixed connective tissue disease who are pregnant to consult an obstetrician and a rheumatologist with experience in treating other patients in similar conditions. The most important tool in the treatment of individuals with mixed connective tissue disease is meticulous and frequent reevaluation of patients. Reevaluation includes clinical and laboratory evaluation, allowing prompt recognition and treatment of disease flare that is essential to positive outcome.
As in individuals with systemic lupus erythematosus (SLE), patients may require little or no medication or may require long-term immunosuppression. Some of the medications patients require can be found below. Other specific medications may be applicable if the patient has another disease manifesting with mixed connective tissue disease. Because of the rarity of this disease, advise the patient to consult a physician with experience in the treatment of mixed connective tissue disease. Patients with hypertension should be aggressively treated. If hypertension is a consequence of corticosteroid therapy, consider immunomodulating medications as steroid-sparing agents to help control hypertension. Calcium channel blockers used to treat hypertension may also be used to treat Raynaud phenomenon.
For more information, see Hypertension.
Nonsteroidal anti-inflammatory drugs
Class Summary
For children who present with mild disease, treat symptomatically and monitor closely for signs of disease progression. Treat individuals with arthritis and musculoskeletal pain with nonsteroidal anti-inflammatory drugs (NSAIDs).
Select a specific agent based on patient response to medication, history of previous drug allergy or reaction, and ease of use. These medications have analgesic and anti-inflammatory properties to treat arthralgia and arthritis and are available with slightly different safety and efficacy profiles.
Naproxen (Aleve, Naprelan, Naprosyn, Anaprox)
For relief of mild to moderate pain; inhibits inflammatory reactions and pain by decreasing activity of cyclooxygenase, which is responsible for prostaglandin synthesis. Available in SR formulation for once daily dosing as Naprelan.
Tolmetin (Tolectin)
For relief of mild to moderate pain; inhibits inflammatory reactions and pain by decreasing activity of cyclooxygenase, which is responsible for prostaglandin synthesis.
Diclofenac (Voltaren-XR)
Inhibits prostaglandin synthesis by decreasing activity of enzyme cyclooxygenase, which decreases formation of prostaglandin precursors.
Available in SR formulation as Voltaren-XR (100 mg).
Antimalarials
Class Summary
Patients in whom major disease manifestation is lupus, rash, and other minor symptoms can be treated with hydroxychloroquine.
Hydroxychloroquine (Plaquenil)
Antimalarial drugs inhibit synthesis of DNA, RNA, and proteins by interacting with nucleic acids. Antimalarial drugs have various immunosuppressive effects, can act as antioxidants, and interfere with prostaglandins. Hydroxychloroquine sulfate 200 mg is equivalent to 155 mg hydroxychloroquine base and 250 mg chloroquine phosphate.
Corticosteroids
Class Summary
Use corticosteroids to treat children with hypocomplementemia and elevated levels of anti-DNA antibodies, children with active myositis, and children with significant manifestations of scleroderma. Dose varies with intensity of disease activity. Consider daily prednisone (1 mg/kg/d) or higher-dose alternate-day prednisone (5 mg/kg/d, not to exceed 150-250 mg depending on size of patient). Alternatively, lower-dose daily prednisone (0.5 mg/kg) may be used in conjunction with intermittent high-dose IV methylprednisolone (30 mg/kg/dose, not to exceed 1 g) on a weekly basis. Of note, recent case reports suggest that 3 days of pulse IV methylprednisolone followed by moderate-to-high dose oral steroids improved pulmonary artery pressures in a patient with mixed connective tissue disease and pulmonary artery hypertension.
Prednisone (Deltasone, Orasone), Methylprednisolone (Adlone, Solu-Medrol)
Decreases inflammation by suppression of immune system: decreased lymphocyte volume and activity; decreased PMN migration; decreased or reversal of capillary permeability. High doses, especially over periods longer than 2-3 wk, suppress adrenal function.
Immunosuppressive agents
Class Summary
Evaluate children with signs of active nephritis to determine World Health Organization (WHO) classification category of their nephritis. For patients with class IV nephritis and some patients with class III nephritis, treat with corticosteroids and cyclophosphamide. Use azathioprine for individuals with milder nephritis. Use methotrexate for persons with arthritis not controlled by NSAIDs and for persons with fibrosis, especially sclerodermatous skin. Consider cyclophosphamide for individuals with severe systemic involvement of other vital organs, especially brain and lung. Consider other agents (eg, mycophenolate mofetil, cyclosporine) when standard therapies have failed. Other treatments under study include hormonal therapy, biologic agents that target cytokine production, and anti-DNA antibodies. For patients with severe persistent disease, autologous and stem cell transplantation is under study.
Cyclophosphamide (Cytoxan, Neosar)
Interferes with normal function of DNA by alkylation and cross-linking strands of DNA and by possible protein modification.
Azathioprine (Imuran)
Antagonizes purine metabolism and may inhibit synthesis of proteins, RNA, and DNA. May interfere with mitosis and cellular metabolism.
Methotrexate (Rheumatrex)
An antimetabolite that interferes with enzyme dihydrofolate reductase, leading to depletion of DNA precursors and inhibition of DNA and purine synthesis, particularly adenosine.
Calcium and vitamin D therapies
Class Summary
All patients who are on corticosteroids or who have arthritis are at greater risk for osteopenia and its complications. Diet and appropriate supplementation with vitamin D and calcium are important tools for bone health in these patients.
Calcium carbonate (Oystercal, Caltrate)
Used as antacid and for prevention of calcium depletion.
Calcifediol (Calderol)
Vitamin D regulates calcium homeostasis, promoting absorption of calcium by gut, resorption of calcium by kidney, and increasing bone mineral metabolism.
Rheostatic agents
Class Summary
These agents are used to improve peripheral blood flow and to improve delivery of oxygen to tissue suffering from peripheral vascular disease. In individuals with mixed connective tissue disease, used to decrease symptoms and damage from Raynaud phenomenon.
Pentoxifylline (Trental)
Methylxanthine used as hemorheologic agent by improving flow properties of blood by decreasing viscosity, which improves oxygenation to peripheral tissues. Precise mode of action is not defined; however, produces dose-related hemorheologic effects, lowering blood viscosity and improving erythrocyte flexibility. Another benefit is ability to increase leukocyte deformability and to inhibit neutrophil adhesion and activation.
Phosphodiesterase (type 5) Enzyme Inhibitor
Class Summary
These agents increase peripheral vasodilation and may be helpful in treating symptoms associated with Raynaud disease.
Sildenafil (Revatio)
Inhibits phosphodiesterase type 5 in smooth muscle of pulmonary vasculature in which phosphodiesterase type 5 is responsible for the degradation of cGMP. Increased cGMP concentration results in pulmonary vasculature relaxation; vasodilation in the pulmonary bed and the systemic circulation (to a lesser degree) may occur. The systemic vasodilation may be helpful to reduce Raynaud disease symptoms.
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Raynaud phenomenon showing demarcation of color difference.
