The patient, male, aged 50, began to have the skin hardening and Raynaud's phenomenon of both hands in 2005, accompanied by oral ulcer and hair loss, which was not paid attention to and treated. After that, the above symptoms worsened. He was treated in our hospital in September 2018. The physical examination showed that the fingers of both hands were swollen and hard, and the skin was not easy to twist. The laboratory examination showed that the anti nuclear antibody was 1:100+, and the anti ScL-70 antibody was 35.92 Ru/ml, Lung CT: pulmonary interstitial fibrosis changes under both sides. He was diagnosed as "systemic sclerosis and connective tissue related interstitial lung disease", and was treated with prednisone, cyclophosphamide, beraprost and nifedipine. After improvement, he was not used regularly. In 2019, he suffered from repeated hemoptysis, initially with blood filaments in sputum. Later, the amount of hemoptysis gradually increased, accompanied by dizziness and exertion. He was treated symptomatically outside the hospital for many times. On February 4, 2021, he eveloped severe cough and hemoptysis after catching cold, and felt shortness of breath, palpitation and fatigue. He was treated in our hospital. His blood pressure was 123/74mmHg. Physical examination: high pillow lying position, anemia appearance, tight facial skin, pale eyelid conjunctiva, shallow nasolabial groove, thin and pale lips, and dullness of percussion of both lower lungs, The breath sounds are rough, and wet rales can be heard. The skin temperature of both hands is low. The joints between fingers are swollen. The skin of both hands is thickened and hardened, which is difficult to lift and pinch, and concave scars can be seen between fingers. Laboratory examination: PO2 70mmhg; Routine blood test: leukocyte 13.81×109/L, neutrophils 13.03×109/L (94.3%), lymphocytes 0.57×109/L (4.2%), erythrocyte 1.9×1012/L, Hemoglobin 57g/L, Platelet 151×109/L; ESR 9mm/h; hsCRP 257. 21mg/L; Renal function: Urea 10.4mmol/l, Creatinine 143umol/L; Urine routine: protein 1+, occult blood 3+, leukocyte count 16/UL, erythrocyte count 431/UL, percentage of abnormal erythrocyte in urine 70% (40% of shrunken red blood cells, 10% of shadow, spore and small red blood cells respectively); Stool routine: occult blood (+); D-dimer 4.25UG/ml; ANA 1:320+, anti ScL-70 antibody 221.66 Ru/ml; p-ANCA 1:10+, MPO-ANCA 107.41RU/ml. Chest CT: large shadow can be seen in both lungs with unclear boundary, and air bronchial signs can be seen in them, suggesting interstitial lesions with multiple infectious lesions and a small amount of bilateral pleural effusion. Abdominal ultrasound showed peritoneal effusion. Cardiac ultrasound showed a trace of pericardial effusion.He was diagnosed as "systemic sclerosis, connective tissue related interstitial lung disease, double lung pneumonia, microscopic polyangiitis, renal insufficiency, multiple serous cavity effusion and severe anemia", and was treated with anti infection, hemostasis, blood transfusion, promoting hematopoiesis and protecting the kidney. There was dark red blood many times during the treatment. The blood routine of the patient was rechecked on February 9: leukocyte 8.51×109/L, neutrophils 6.32×109/L (74.4%), lymphocytes 0.83×109/L (9.7%), erythrocyte 1.58× 1012/L, hemoglobin 46g/L; ESR 48mm/h; hsCRP 48.02mg/L; Renal function: urea 6.24mmol/l, creatinine 115.2umol/l; PO2 67mmhg; Chest CT showed that there was no significant change in bilateral lung lesions. After treatment, the number of erythrocyte, hemoglobin and oxygen partial pressure decreased gradually, and the degree of hypoxia increased, and the anemia was positive cytochrome, which was not parallel to the injury of renal function and considering caused by hemoptysis. The hemoptysis symptoms and imaging results could not be fully explained due to pulmonary infection, considering the combination of alveolar hemorrhage. His severe condition could not cooperate with the improvement of pulmonary function and fiberoptic bronchoscopy biopsy Renal biopsy. She was eventually diagnosed with pulmonary renal syndrome. After the comprehensive evaluation of the patient's condition, he was added with "methylprednisolone 240mg qd, cyclophosphamide 0.2g qod and pirfenidone 200mg tid". After 3 days, the methylprednisolone was reduced to 80mg qd, and the cyclophosphamide infusion was stopped after 1.2g. After that, the patient stopped hemoptysis, and the symptoms of cough and shortness of breath improved. On February 25, the erythrocyte was rechecked for 3.13×1012/L, hemoglobin 95g/L, renal function and other indicators returned to normal (Fig. 1). Chest CT showed bilateral pulmonary exudative lesions and obvious absorption of pleural effusion (Fig. 2). After discharge, he took prednisone 50mg qd, nifedipine 30mg qd and pirfenidone 300mg tid orally, and was infused with cyclophosphamide every month. The glucocorticoid was gradually reduced and his condition was stable. So far, he has been followed up in the outpatient department of our hospital.
Literature Review
In addition to the case reported here, we performed a MEDLINE search of all reports, articles, and reviews that had been published, using “microscopic polyangitis” and “pulmonary renal syndrome” and “scleroderma” or “systemic sclerosis” as search words. All relevant articles were carefully reviewed, and the data were summarized. We retrieved 7 relevant literatures, all of which were case reports. A total of 9 patients were reported, including 2 males (22%) and 7 females (78%), with an average age of 58.1 years ( range 43–72 years). Among them, 6 cases were diffuse cutaneous systemic sclerosis, 2 cases were limited cutaneous systemic sclerosis and 1 case was overlapping syndrome, all of which were first diagnosed as SSc and then MPA and PRS. The average time interval from the onset of SSc to the onset of PRS was 14.6 years (range 5 ~ 30 years). Among the 9 patients, all had interstitial lung disease, 7 were positive for anti-Scl-70 antibody, and 6 underwent renal biopsy. All showed Crescentic Nephritis. Glucocorticoids, immunosuppressants, ACEI, rituximab, hemodialysis and plasma exchange were the main treatments. 4 cases improved after treatment and 5 cases died. It should be noted that among the dead cases, 3 cases received D-penicillamine before the onset of PRS, and the remaining 2 cases only received glucocorticoid and / or hemodialysis, seeing Table 1 for clinical data.
Characteristic
|
Case No. Author (Reference)
|
1.Liu et al[1]
|
2.Wutzl et al[2]
|
3.Arad et al[3]
|
4.Arad et al[3]
|
5.Tonneijck et al[4]
|
6.Inada et al[5]
|
7.Miyata et al[6]
|
8. Endo et al[7]
|
9. Endo et al[7]
|
Age (yr)/sex
|
48/F
|
43/M
|
63/F
|
55/F
|
72/M
|
62/F
|
67/F
|
47/F
|
66/F
|
Duration of disease
(yr)
|
11
|
18
|
11
|
30
|
10
|
26
|
14
|
6
|
5
|
SSC subset
|
LcSSc
|
DcSSc
|
DcSSc
|
LcSSc
|
DcSSc
|
OLS(SSc+DM+SLE)
|
DcSSc
|
DcSSc
|
DcSSc
|
D-PCN treatment (yr)
|
No
|
No
|
Yes (3)
|
No
|
No
|
No
|
Yes
|
Yes
|
No
|
Fever
|
No
|
Yes
|
NA
|
NA
|
No
|
No
|
Yes
|
Yes
|
NA
|
Normotensive renal failure
|
No
|
Yes
|
NA
|
Yes
|
No
|
Yes
|
Yes
|
No
|
No
|
BP; Cr
|
150/90; 807.09
|
135/70;187
|
NA;247.52
|
138/65; 335.92
|
170/90; 67
|
128/80; 344.76
|
100/70; 185.64
|
202/108; 459.68
|
154/80; 839.8
|
Clinical features
|
Hemoptysis,
Anemia,
|
Hemoptysis,
Anemia,
|
Hemoptysis,
Anemia,
|
Hemoptysis,
Anemia,
|
Hemoptysis,
Anemia,
|
Anemia
|
Anemia
|
CHF, Anemia
|
Anemia
|
ANA
|
ANA(+),Scl-70(+)
|
ANA(+), SSA(+),SSB(+)
|
ANA(+),Scl-70(+)
|
ANA(+),Scl-70(+)
|
Scl-70(+)
|
ANA(+), LE(+), RNP(+)
|
ANA(+),Scl-70(+)
|
ANA(+), Scl-70(+), RNP(+), DNA(+)
|
ANA(+), Scl-70(+), RNP(+), DNA(+)
|
ANCA
|
p-ANCA (+), MPO-ANCA(+)
|
p-ANCA(+), MPO-ANCA (+)
|
p-ANCA(+)
|
p-ANCA (+), MPO-ANCA (+), GBM(+)
|
p-ANCA (+), MPO-ANCA(+)
|
MPO-ANCA(+), GBM(+)
|
MPO-ANCA(+)
|
p-ANCA (+)
|
p-ANCA (+)
|
Pulmonary features
|
DAH,IF
|
DAH,IF
|
DAH,IF
|
DAH,IF
|
DAH,IF
|
DAH,IF
|
DAH,IF
|
DAH,IF,CAP
|
prior IF
|
Renal pathology
|
Cresc
|
Cresc, FSNGN
|
NA
|
Cresc,GS
|
NA
|
Cresc,GS
|
Cresc
|
Cresc, Cap
|
NA
|
Diagnostic sequence
|
SSC→MPA、PRS
|
SSC→MPA、PRS
|
SSC→MPA、PRS
|
SSC→MPA、PRS
|
SSC→MPA、PRS
|
SSC→MPA、PRS
|
SSC→MPA、PRS
|
SSC→MPA、PRS
|
SSC→MPA、PRS
|
Treatment
|
CS,CYC,PP, HD
|
CS,CYC,AZA
|
MV, Pulse CS,CYC,PP
|
Pulse CS, CYC, PP, HD, Rituximab
|
CS,CYC,PP,Rituximab
|
CS, HD
|
Pulse CS
|
CS
|
HD
|
Outcome
|
Remission
|
Remission
|
Death 2 weeks after admission
|
Remission
|
Remission
|
Death within 6 months
|
Death a few days
after admission
|
Death within 6
months
|
Death within 6 months
|
Abbreviations: F, female;M, Male; SSc, systemic sclerosis; LcSSc, limited cutaneous systemic sclerosis; DCSSc, diffuse cutaneous systemic sclerosis; OLS, overlapping syndrome; DM, dermatomyositis; SLE, Systemic Lupus Erythematosus; D-PCN, D-penicillamine; NA, not available; BP, blood pressure (mm Hg); Cr, serum creatinine (μmoI/L); ANA, antinuclear antibodies; Scl-70, anti-Scl-70 antibodies; SSA,anti-SSA antibody;SSB, anti-SSB antibody; LE, lupus erythematosus cells; RNP, anti- ribonuclear protien antibody; p-ANCA, antineutrophil cytoplasmic antibodies; MPO-ANCA, anti-myeloperoxidase antibodies; GBM, glomerular basement membrane; DAH, diffuse alveolar hemorrhage; IF, interstitital fibrosis; CAP, capillaritis; Cresc, crescents; Cap, capillary loop necrosis; FSNGN,focal segmental necrotising glomerulonephritis; GS,glomerulosclerosis; MPA, Microscopic polyangitis; PRS, Pulmonary renal syndrome; CS, corticosteroids; CYC,cyclophosphamide; PP, plasmapheresis; HD, hemodialysis; AZA, Azathioprine; PP, plasmapheresis.