Long-term rituximab treatment of refractory idiopathic inflammatory myopathy: A report of 3 cases / 北京大学学报(医学版)

Idiopathic inflammatory myopathies are a group of rare but serious diseases. The treatment of refractory idiopathic inflammatory myopathy is always challenging, especially in children. Three cases of refractory idiopathic inflammatory myopathy treated by rituximab were reported and discussed with the review of relevant literature. All were female with on-set age of 8 years and 6 months, 11 years and 7 months, 4 years and 2 months old, respectively. All had acute onset, presenting with progressive and severe muscle weakness. All lost ambulation within 1 or 2 months, with difficult swallowing and low voice. Respiratory distress occurred in case 2 after an attack of asphyxia due to an aspiration of sputum, and ventilator support was required for 1 month. Rashes were detected at the initial stage of the disease in cases 2 and 3. Patient 2 showed facial erythematous papules, spreading to her neck and hands. Patient 3 showed purplish eyelids with peri-orbital swelling, generalized edema involving all her limbs. Creatine kinase (CK) levels were markedly elevated in all the patients, ranging from 6 000 IU/L to 28 819 IU/L. Anti-SRP antibody was identified in cases 1, and anti-NXP2 antibodies were confirmed in cases 2 and 3. MRI of both thighs in all the patients showed profound muscle and fascial edema. Muscle pathology of patient 1 showed prominent fiber variation and endomysial fibrosis, with overexpression of MHC-Ⅰ. While muscle pathology in patients 2 and 3 showed scattered fiber necrosis, regeneration, endomysial edema without inflammatory cell infiltration. All the patients were diagnosed with idiopathic inflammatory myopathy and failed to the initial treatment including adequate glucocorticoids and high-dose immunoglobulin therapy. Other immunosuppressants (methotrexate, cyclophosphamide) were also tried in cases 2 and 3 with poor response. Then all the patients were treated with rituximab combined with glucocorticoids. Patient 1 regained normal strength and discontinued rituximab at the end of her last follow-up (2 years and 7 mouths). Though calcinosis developed during the follow-up period, significant improvement was noticed in cases 2 and 3 (both regained the ability to walk independently) at the end of their last follow-up after 2 years and 8 months, 3 years and 2 months respectively. Long-term rituximab therapy may improve the prognosis of refractory idiopathic inflammatory myopathy, especially with positive anti-SRP and anti-NXP2 antibodies.

Regulating effect of endogenous carbon monoxide on brain damage induced by recurrent febrile seizures through GRP78-PERK-eIF2α-CHOP signal pathway / 中华实用儿科临床杂志

Objective To observe the effect of endogenous heme oxygenase 1 (HO-1)/carbon monoxide(CO)system on brain damage induced by recurrent febrile seizures (FS) through GRP78-PERK-eIF2α-CHOP signal pathway.Methods Forty-eight SD male rats of 21 days were randomly divided into 4 groups:control group,FS group,FS with ZnPP-Ⅸ (FS + ZnPP-Ⅸ) group,and FS with Hemin(FS + Hemin) group,12 rats in each group.Hyperthermia treatment was carried out 10 times,once every 2 days.For group FS + Hemin,Hemin,a CO donor was administered intraperitoneally 0.5 hour before each immersion.For group FS + ZnPP-Ⅸ,ZnPP-Ⅸ,an inhibitor of HO-1 were preconditioned intraperitoneally 0.5 hour before each immersion.The seizure latency,seizure intensity and seizure duration of FS rats were recorded.The content of CO in cortex was measured by using dual wavelength spectropotometey.Neuron apoptosis was detected by using TUNEL.The expressions of GRP78,p-PERK,p-eIF2α and CHOP in cortex were measured by using immunohistochemistry.Results No difference in the seizure latency,seizure intensity and seizure duration in the rats FS + ZnPP-Ⅸ group or the FS + Hemin were recorded,compared with those in the FS group(all P ＞0.05).The content of CO in cortex increased after recurrent FS (P ＜ 0.05).The generation of CO further up-regulated the expressions in FS + Hemin group,while it decreased the expressions in FS + ZnPP-Ⅸ group(all P ＜0.05).Neuronal apoptosis was evident in the FS group.Hemin reduced neuronal apoptosis,up-regulated the expression of GRP78,down-regulated the contents of CHOP,p-PERK and p-eIF2α ;ZnPP-Ⅸ further induced neuronal apoptosis,and down-regulated the expression of GRP78;it aslo up-regulated the expression of CHOP,p-PERK and p-eIF2α.Conclusions Endogenous HO-1/CO system protects the rats from brain damage induced by recurrent FS through endoplasmic GRP78-PERK-eIF2α-CHOP/GADD153 signal pathway.