PMC6421146_01
The clinical course of rheumatoid vasculitis. Unstable arthralgia (B) under MZR, SASP, ETN, and PSL (D) was completely controlled by ADA, with no SJCs or TJCs (B) and a low DAS28 score (C). The high VAS score from 2014 (A) was due to dysesthesia of the toes, cough, and dyspnea, not arthralgia. Consequently, ADA was reduced from August 2015, as his arthritis was stable. ADA: adalimumab, DAS: disease activity score, ETN: etanercept, MZR: mizoribine, SASP: salazosulfapyridine, SJC: swollen joint count, TJC: tender joint count, VAS: visual analogue scale
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The clinical course of the patient is shown in Fig. 1, 2.
Activity of pulmonary hypertension and inflammatory markers. (A) Six months after ADA reduction in February 2016, the TRPG had increased to 60 mmHg, indicating the onset of PH crisis. The TRPG increased to 62 mmHg on day 8 and 110 mmHg on day 17 with elevation of the BNP level. (B) The CRP levels correlated well with the severity of PH, but the ESR gradually increased, and the C4 decreased from 2013. (C) The levels of RF and ACPA were extremely high at the time of PH crisis. KL-6 and MMP3 were not useful as predictors of worsening PH. BNP: brain natriuretic peptide, C4: complement C4, ACPA: anti-cyclic citrullinated peptide antibodies, CRP: C-reactive protein, ESR: erythrocyte sedimentation rate, KL-6: Krebs von den Lungen 6, MMP3: matrix metalloprotenase-3, RF: rheumatoid factor, TRPG: tricuspid regurgitation pressure gradient
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The clinical course of the patient is shown in Fig. 1, 2.
Clinical images during PH worsening. Chest X-ray (A-C) shows worsening of cardiomegaly. Chest computed tomography shows dilated pulmonary arteries (D) and mild interstitial lung disease (E). Trans-thoracic echocardiography (F-H) detects a D-shaped left ventricle. Brain MRI (FLAIR) shows multiple old cerebral infarctions (I, J)
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Chest X-ray (Fig. 3A-C) and chest computed tomography (CT) (Fig. 3D and E) showed persistent ILD findings in the bilateral lower lobes. Echocardiography detected a D-shaped left ventricle (Fig. 3F and H) and elevated TRPG (70 mmHg). He was diagnosed with rheumatoid vasculitis based on mononeuritis multiplex, ILD, asymptomatic cerebral infarctions (Fig. 3I and J), and a high level of RF on a background of chronic RA. Chest X-ray (Fig. 3A-C) and CT (Fig. 3D and E) showed worsening of cardiomegaly and persistent mild ILD findings. Echocardiography showed progression of left ventricular compression forming a D-shape (Fig. 3F-H).
Time course of ECG after PH development. Electrocardiography shows SIQIIITIII and severe right axis deviation on day 18. According to the time course, ICRBBB changed to CRBBB. The negative T wave of V1-V4 indicates right ventricular load. ICRBBB: incomplete right bundle branch block, CRBBB: complete right bundle branch block
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Electrocardiogram (ECG) (Fig. 4) showed incomplete right bundle branch block. ECG revealed SIQIIITIII, severe right axis deviation, complete right bundle branch block, and negative T wave of V1-V4, indicating right ventricular load (Fig. 4).
Pathologic findings of pulmonary arteries in rheumatoid vasculitis. Micro-thrombi (A, B; *), perivascular inflammation (C), and degradation of the elastic lamina (D; *) are observed in the acute inflammatory area. In the adventitia, the majority of inflammatory cells are neutrophils (E;  ) with a few lymphocytes (E;  ) infiltrating the vessel wall (E;   ). Clusters of macrophages (E, F; *) and neutrophils (F; **) intersect in the vessel lumen (F;   ). Around the progressively remodeled vessel (G), the majority of inflammatory cells are lymphocytes (H) with a few neutrophils (H;  ). Hematoxylin and Eosin (A, B, E-H) and Elastica van Gieson (B, D) staining.
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The pathological findings from the autopsy revealed micro-thrombi (Fig. 5A and B) in pulmonary arteries with perivascular inflammation, which was compatible with vasculitis. Around the mildly remodeled artery (Fig. 5C and D), indicative of acute inflammation, neutrophils with a few lymphocytes had infiltrated into the vessel wall (Fig. 5E and F). In contrast, around the progressive remodeled artery (Fig. 5G, 6A and B), indicative of chronic inflammation, the majority of the inflammation cells were lymphocytes (Fig. 5H).
The characterization of perivascular lymphocytes. Around the moderately remodeled pulmonary artery (A, B; *), both T (C) and B (F) lymphocytes are recognized in the perivascular space. In the T cell fraction, CD8+ cytotoxic T cells (E) are more abundant than helper T cells (D). Hematoxylin and Eosin (A) and Elastica van Gieson (B) staining.
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In contrast, around the progressive remodeled artery (Fig. 5G, 6A and B), indicative of chronic inflammation, the majority of the inflammation cells were lymphocytes (Fig. 5H). In addition, both T (Fig. 6C) and B (Fig. 6F) lymphocytes were observed in the perivascular space. CD8+ cytotoxic T cells (Fig. 6E) were more abundant than CD4+ helper T cells (Fig. 6D) on immunohistochemical staining.