I would use CellCept and low dose prednisone for SLE-like symptoms. There is no good data on scleroderma-like symptoms. CellCept and MTX could be considered.

Yes I would use methotrexate or leflunomide for their arthritis, possibly with low-dose corticosteroids.  This has worked well in my experience.  I would also start hydroxychloroquine to reduce risk of flares.

Dear Grant,

I am glad to read your answer as expected, and use corticosteroids together, too. Hydroxychloroquine is interesting, but unfortunately, now we can not use it in Japan.

Well, do you use the immunosuppressive drug for MCTD without arthritis?

Thank you so much.

Dear Imtiyaz,

YES, I THINK SO.

Thank you so much.

Dear Dr. Wakiguchi 

of course Methotrexate and low dose of prednisone are the best way in case arthritis and myositis in MCTD. 

Dear Dr. La Torre

I appreciate your opinion.

Well, what is the best immunosuppressive drug in case systemic lupus erythematosus or scleroderma-like symptoms in pediatric MCTD?

Thank you so much.

I would use CellCept and low dose prednisone for SLE-like symptoms. There is no good data on scleroderma-like symptoms. CellCept and MTX could be considered.

Dear Patompong,

I am delighted to receive a convincing answer.

Mycophenolate mofetil (MMF) is one of the candidate. I believe that MMF may be the appropriate treatment for not only SLE-like symptoms but also MTX-resistant myositis-like symptoms.

It is difficult to reach the consensus of the best immunosuppressive therapy for scleroderma-like symptoms. I would love to get some good feedback on that.

Thank you so much.

Low dose steriod Is enough

Dear Mohammed,

It could be one of the choice.

However, there are some cases not enough.

For example, although low dose steroid was used in our case, myositis-like symptoms flared up, and serum creatine kinase levels increased to 3,000 IU/L.

Thank you so much.

I am delighted to be part of this question regarding choice of immunosuppressives in MCTD. Opinion from different literature is that you have to address the clinical characteristics which is predomnant and should treat accordingly. Millions of thanks

i would use hydroxychloroquin, low dose steroids. apart from this, the other DMARD would be methotrexate if there is no ILD, and azathioprine/mycophenolate in case of ILD. methotrexate at first choice because of prominence of articular symptoms.

Dear Sujat,

That's right.

Thank you so much.

Dear Bijit,

I appreciate your detailed description.

Your suggestion is reasonable.

Thank you so much.

Does anyone have any comments on that?

MCTD is uncommon in children. When followed for many years most children with so-called MCTD will evolve to a single definable rheumatic disease. Most commonly; dermatomyositis, SLE, or systemic sclerosis. Fortunately most do not develop serious renal disease. I agree with the comment regarding treating the most prominent features of the disease. NSAIDs for arthritis, corticosteroids for dermatomyositis and SLE, methotrexate for steroid sparing, and cytotoxic drugs for life, organ threatening disease.

Dear Donald,

I appreciate your detailed description.

Your suggestion is also reasonable.

Thank you so much.

P.S.

Please see the following article about renal disease of pediatric MCTD.

Ito S, Nakamura T, Yokota S, et al. Glomerulonephritis in children with mixed connective tissue disease. Clin Nephrol 2006; 66: 160-5.

Pediatric MCTD is known to be associated with a higher risk of nephritis than adult MCTD. Membranous nephropathy and mesangial proliferative glomerulonephritis were common in pediatric MCTD. The hypocomplementemia observed in children with MCTD suggests the high frequency of glomerulonephritis, including membranous lesions.

Dear All,

Provisional Conclusion

Mild disease manifestations → Hydroxychloroquin

Severe disease manifestations → Cytotoxic drugs

Arthritis → MTX or LEF and/or low dose corticosteroids

SLE-like symptoms → MMF and/or low dose corticosteroids

Myositis-like symptoms → MTX and/or low dose corticosteroids

Scleroderma-like symptoms → MTX or MMF and/or low dose corticosteroids

With ILD → AZP or MMF

Without ILD → MTX

Prevention of flares → Add hydroxychloroquine

Sincerely,

Hiroyuki Wakiguchi

MCTD is treated according to manifestations/organ disease.

In your patient there is arthritis and myositis.

Arthritis responds nicely to methotrexate which is remarkably well tolerated by children.

The real issue is how bad the myositis is.

Usefulness of methotrexate for myositis is very inconsistent.

Oral and/or IV pulse steroids are advocated. But I do not think they are the answer. We cannot keep a child indefinitely on this class of drugs; and we know that the child will require maintenance therapy for ever, on some drug.

It seems reasonable to give steroids as “shuttle therapy” for a short period until the immunosuppressive drug takes effect. The question is which immunosuppressive drug.

1. It seems reasonable to start with the least toxic immunosuppressor, i.e. Azathioprine. It has the advantage of dosage flexibility: starting with 3mg/kg/day, it could be tapered to 1 mg/kg/day on the long run. This is remarkably well tolerated.

2.  If this fails,  one can go to pulse Cyclophosphamide, with pulse methyl-prednisolone.  Cyclophosphamide is indicated for life-threatening organ complications (kidney, brain..) but refractory polymyositis is one. The child could die of respiratory muscle failure.

3. Or to Mycophenolate mofetil.

4. Or off-label use of Rituximab . This might be justified due to encouraging results in adults and less toxicity than Cyclophosphamide.

Dear Majda,

This is splendid.

Your flowchart is very reasonable and useful.

Actually, in our case, 2 courses of methylprednisolone pulse therapy (1 course = 30 mg/kg/day × 3 days/week) were administered. The effectiveness was good. The arthritis and myositis-like symptoms were improved, and creatine kinase levels were normalized. We added MTX (10mg/m2/week) as well as oral prednisolone (1mg/kg/day) after methylprednisolone pulse therapy, and now prednisolone is tapering without flares.

Thank you so much.

Dear Ibrahim,

I admit the justice of your argument, but it sometimes becomes the vicious circle. In other words, starting with low doses could lead to repetitive flares and need additional doses. In such cases, organ damages become advanced, and side effects of drug increase.

On the other hand, severe complication is more common in pediatric MCTD than in adult MCTD. Initial aggressive immunosuppressive therapy therefore may reduce flares and total dosage, especially in children.

Thank you so much.

High-dose mycophenolate mofetil (600mg/m2/dose twice daily) along with monthly infusions of abatacept (10mg/Kg/dose). If the patient has a systemic sclerosis-like phenotype and anti-Scl70 positivity, I would not use any corticosteroids due to concerns about renal crisis.

Dear Ioannis,

Thank you for your advanced suggestions.

Abatacept is interesting.

Corticosteroids use may be associated with an increased risk of developing renal crisis in the patients with scleroderma-like symptoms.

Thank you so much.