In 2018, a 2-year-old male presented with intermittent low fever, accompanied by pale red papules, facial edema, and night snoring. He was hospitalized in a local hospital and received cefazoxime without improvement. Later, the patient was transferred to the Children's Hospital affiliated to Fudan University due to fever. The results showed that ALT was 120 IU/L and AST was 284 IU/L. Epstein-Barr virus IgG, ANA and anti-nucleosome antibody was positive. The patient was diagnosed as "abnormal liver function and erythema multitype". Body temperature was normal after 3 days of methylprednisolone impact therapy. Medrol 4-12mg was taken after discharge. A month later, high fever occurred again, with a temperature of 39.4℃, accompanied by convulsions, two eyes up, weakness of limbs, and foaming at the mouth, which resolved spontaneously about 5 minutes later. A large amount of facial rash followed by facial edema, red and dry lips, conjunctival congestion, left neck mass, and oral ulcer. EEG diagnosis at the local hospital showed moderate abnormalities, no epileptic discharge. After 3 days of treatment with methylprednisolone 12mg/d and clindamycin 0.15g twice a day, the patient still had fever. The patient was referred to our facility. At admission, he still had a low fever and a rash scattered on both inner thighs.
Physical examination was found that pharyngeal mucosa was congested and bilateral tonsils were II degree swollen. The lips were dry red and chapped, the oral mucosa was ulcerated, and the conjunctiva of both eyes was congested. The face was swollen, and a large number of red spots could be seen on the face, which were partially fused and higher than the skin (Figure 1A). Several soybean sized lymph nodes could be touched under the right armpit, with medium quality and moderate activity.
Serology demonstrated high titer anti-nuclear antibodies (ANA; Hep2 titer 1280), anti-double-stranded deoxyribonucleic acid (anti-dsDNA; titer 10). antimitochondrial antibody (AMA) M2, Ro-52 and anti-nucleosome antibody were positive. The level of ferritin was high (704.2ng/ml). Plain computed tomography (CT) scan of chest showed pneumonia with a small amount of pleural effusion on both sides (Fig. 2). Brain magnetic resonance imaging (MRI) showed Flaky FLAIR high signal in the posterior portion of bilateral lateral ventricles with widening of sulci in hemispheres and significant sulci in cerebellum (Fig. 3). Neck skin biopsy light microscope examination showed consistent with the pathological changes of erythema multiforme. Small pieces of skin were examined and the epidermis was found to be focal atrophy and thinning, with a small amount of bad dead corner prion cells, focal basal cells liquefied degeneration, and a small number of lymphocytes and histocytes at the epidermal dermal junction. Immunohistochemical results were CD3+, CD68+, and Ki-67+. Gene detection showed mutations in integrin subunit alpha M (ITGAM) (c.1592A > G, p.N531S; c.3213G > C, p.E1071D) and complement component 1 (C1)s (c.217-5T > G, splicing).
After hospitalization, he was given ertapenem for anti-infection and Compound Ammonium Glycyrrhizinate for liver protection. Intravenous immunoglobulin (IVIG) was given 2g/kg, actually 5g for 5 days. After adding methylprednisolone 2mg/kg/d, the thermal peak decreased. On the 7th day of admission, ertapenem was stopped and changed to cefamandole 0.5g, twice a day for anti-infection treatment. Then the child developed intermittent fever, the blood routine three systems decreased and the transaminase increased. It is considered that there may be early macrophage activation syndrome. The patient was treated with methylprednisolone 0.36g (27mg/kg), IVIG 5g, cyclosporine 50mg via intravenous drip. After 5 days of treatment, the overall situation of the children was significantly improved compared with that before admission. The patient can eat from his mouth and pull out his stomach tube. Then the patient was given prednisone acetate tablets 2mg /kg/d actually 27.5mg/d orally. Tofacitinib was given 2.5mg, 2 times a day. After one week of treatment, the body temperature was normal and the rash was significantly relieved (Fig. 1B). In addition, the inflammatory indicators were improved, and the lesions on chest radiographs were less than before. Tofacitinib was then used for about a year, and was switched to belimumab combined with IVIG and glucocorticoid. His condition has been stable for nearly a year without fever or rash.
In 2019, a 2-year-old female was hospitalized with a rash and recurrent fever. At 6 months after birth, the child developed a round red skin rash on the face, alopecia, and subsequent leg pain. 3 months before admission, rash appeared all over the body, accompanied by fever, once a day. Physical examination showed scattered irregular red rash on the face and hands, and old brown rash on the trunk and limbs. The lower extremities were slightly stiff, the knees and ankles were swollen without tenderness, and the right dorsum was edema. Both lower limbs movement is limited, cannot squat. Unsteady walking, walking on tiptoes.
Physical examination: scattered old brown rash could be seen on the trunk and limbs. Bilateral muscle strength was normal. Double knee and double ankle joints were swelling, the right foot dorsum was edema. Babinski signs and ankle clonus were positive with hyperreflexia of tendon.
Laboratory inspection: hemoglobin was 101g/L and platelet was 264×109/L. Inflammatory marker displayed that blood sedimentation and ferritin were high (29 mm/h and 116.3ng/ml, respectively). Antinuclear antibody was 1:1000. anti-U1 small nuclear ribonucleoprotein (anti-U1-nRNP), Anti-Sm (anti-Sm), anti-Sjgren's-syndrome-related antigen A (anti-SSA), anti-Ro-52, anti-ribosomal P-protein (anti-rRNP) antibodies were all expressed strong positive. Renal pathological examination showed mild mesangial proliferative glomerulopathy. Skin pathological examination showed hyperkeratosis with incomplete keratosis and incontinence of pigment in the papillary layer. Vascular endothelial cells swell. Gene tests showed C1s gene (c.849G > A, p.W283X) mutation. Gene tests also found that her father also had the mutation, but her mother did not. This indicates that the mutation was inherited from the father (Fig. 5).
After hospitalization, the child was diagnosed as early-onset SLE. The patient was given IVIG 400mg/kg/d, 5g/d for 4 days of immune support, methylprednisolone 280mg/d shock therapy for 3 days, and ertapenem for anti-infection. Three days later, methylprednisolone was stopped and methylprednisolone 8mg was given orally twice a day. The blood routine examination showed a decrease in three levels, which was considered to be combined with macrophage activation syndrome. The patient was then given IVIG 2.5g for 3 days, cyclosporine 0.2ml, 2 times a day, 25mg thalidomide and 0.25g mycophenolate mofetil (MMF) once a day orally. One week later, the child's temperature returned to normal without fever, and the rash subsided significantly without new rash. After discharge, the patient continued to receive prednisone acetate 15mg once daily, thalidomide 25mg once daily, and MMF 0.25g once daily. Two year later, the patient's condition did not occur repeatedly.
In 2019, a 4-year-old boy was hospitalized with foamy urine and abdominal enlargement. Four months before admission, abdominal distension appeared, followed by fever, with the highest temperature of 40.0℃, 2–3 thermal peaks every day, scattered red papules on the limbs and trunk. After the child urine foam increased, mouth ulcer. Physical examination showed scattered red papules on the limbs and trunk. The skin is dry and scaly. Abdominal examination showed abdominal distension, with abdominal circumference 58cm. There was concave edema in both lower limbs.
The patient's hemoglobin and albumin were lower than normal (79g/L, 28.1g/L, respectively). C-reactive protein (CRP) was 44.36mg/L. Routine urine examination showed urinary protein and occult blood 2+, white cells and tubular type in urine. The 24-hour proteinuria was 1.803g. CT scan of the lungs showed bronchopneumonia, right interlobar effusion, and little stromal change in the left lung. There were unbalanced nucleoplasm development and unclassified cells in sternal bone puncture. Anti - nuclear antibody, anti-dsDNA and anti-rRNP were positive. Abdominal ultrasound showed large liver and spleen. Positron emission tomography-computed tomography (PET-CT) showed an enlarged spleen and increased fluorodeoxyglucose metabolism in the bone marrow cavity of sternum, spine and pelvis. Genetic tests revealed a mutation in the complement component 3 (C3) gene (c.1508C > T, p.A503V).
After admission, the children were given oral prednisone acetate tablet 10mg, once a day, hydroxychloroquine sulfate tablet 25mg, three times a day to suppress the immune response. Captopril tablet was given 6.25mg, three times a day to reduce urinary protein. IVIG was given 400mg/kg/d, 7.5g continuous for 3 days to regulate immunity. Fresh frozen plasma was given 100ml for 5 days to supplement coagulation factors to prevent hypercoagulability. And dipyridamole 25mg, three times a day was taken orally to prevent platelet aggregation and micro thrombosis. Due to the lung was infected, azithromycin was given orally for 5 days to clear the infection. After 14 days of treatment, there was no fever, foam reduction in urine, edema of lower limbs and abdominal distension. The skin of the whole body is slightly dry, no rash observed. No ulceration of oral mucosa. After discharge, prednisone was given 40mg, once a day; MMF 0.25g, three times a day; captopril 6.25mg, three times a day; dipyridamole 25mg, three times a day. Two years after discharge, regular outpatient visits were made, and the disease did not worsen again.
In 2022, a four-year-old girl developed a skin rash of patchy red macules on the left and right inner corners of her eyes 2 years ago. One month later, she developed a rash on the edge of both outer auricles. The rash was reduced after her parents applied prednisone ointment on their own. Subsequently, she developed a patchy red rash on both sides of his cheeks, accompanied by oral ulcers and bleeding spots on the palate. She was treated with tacrolimus and elloxone and relieved after topical application in Capital Institute of Pediatrics. One year ago, she was admitted to the dermatology clinic of Beijing Children's Hospital and was given topical application of tachlimus and cicyotal. Later, skin pathology revealed lupus erythematosus, and prednisone was taken 27.5mg/d orally. Two weeks ago, complement C3 was 0.74g/L, complement component 4 (C4) was 0.08g/L, and anti-dsDNA test showed positive, titer 1:320.
Physical examination: slightly dry lips, scattered dark red old sunken scars on the face(Fig. 6A-D).
Auxiliary examination: Positive chest X-ray showed increased and blurred texture in the right lung. Ultrasonography of knee joint showed a little effusion in bilateral knee cavity, synovial membrane slightly thick, left side. The results of dynamic electrocardiogram suggested sinus rhythm, sinus arrhythmia, partial sinus tachycardia, single premature ventricular beat, partial triad, ST segment elevation, QTC value greater than 0.46. Ophthalmologic examination showed dark spot above left visual field and poor reliability of binocular examination. Parotid gland ultrasound showed uneven echo in bilateral parotid gland parenchyma. Enhanced CT of the right thigh indicated that the distal great saphenous vein was not uniform in thickness and the wall was slightly thick locally, which was considered great saphenous vein thrombosis. The dermatologic examination was consistent with cutaneous lupus erythematosus. Genetic testing revealed a mutation in the three prime repair exonuclease 1 (TREX1) gene (c.861_864delinsATT, p. L287Lfs).
After hospitalization, prednisone acetate tablets 15mg were given once a day in the morning. Calcium carbonate D3 particles 0.5mg, once a day. As the ECG showed myocardial damage, coenzyme Q10 10mg, twice a day was given to nourish the myocardium. Aspirin 25mg once a day orally was used for anticoagulant therapy. After 2 weeks of treatment, the child's temperature was normal and the rash disappeared completely (Fig. 6E).