PMC7686760_01
Clinical course and changes in the serum ferritin level of the patient. Anti-MDA5-positive dermatomyositis (DM), interstitial lung disease (ILD), and rheumatoid arthritis (RA) were improved after immunotherapy with corticosteroids and tacrolimus (TAC), but neuromyelitis optica (NMO) frequently relapsed from mid-May (in 2019). NMO and ILD were exacerbated after rituximab (RTX) induction. Hyperferritinemia persisted throughout the course of illness. The change of serum ferritin was divided into three segments based on the inflection points: rising (A), plateau (B), and falling (C) phases. (A) Serum ferritin level initially decreased by 30% at the beginning of immunotherapy but kept increasing despite symptomatic improvement of ILD. (B) Serum ferritin level remained high in the period of frequent relapses of NMO. (C) Serum ferritin level drastically dropped after plasma exchange (PLEX). The length of the straight line indicates the duration of symptoms or signs. The thickness of straight lines and the size of circles or rectangles directly indicate clinical severity. The solid line and dotted lines reflect the presence and alleviation of the symptoms, respectively. TM, transverse myelitis; ON, optic neuritis; Lmp, intravenous low-dose methylprednisolone; Hmp, intravenous high-dose methylprednisolone; UTI, urinary tract infection.
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F1
The detailed clinical course of the patient is shown in Figure 1. Nevertheless, serum ferritin level has been gradually increasing up to 1,210 ng/ml after a transient decrease at the beginning of immunotherapy (Segment A in Figure 1). Meanwhile, serum ferritin level constantly remained high at above 1,000 ng/ml (Segment B in Figure 1). Serum ferritin level drastically decreased by 64% (from 1,109 to 399 ng/ml) after PLEX (Segment C in Figure 1).
The initial cutaneous, imaging, and pathological findings of the patient. (A) An erythematous patch with scales was seen in the anterior chest. (B) A diffuse purpuric patch with crusts was seen in the left elbow. (C) The three-phase bone scintigraphy revealed increased uptake in both wrists and interphalangeal joints. (D) Skin biopsy of the chest displayed a couple of small vessels with perivascular inflammatory cell infiltration in the upper dermis (H&E, x100). (E) Thigh MRI showed multifocal infiltrations in the anterior thigh muscles with left side dominancy. (F) Biopsy of the left vastus lateralis muscle revealed a small number of atrophic angular myocytes (arrows) in the perifascicular area (H&E, x100).
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F2
On physical examination, erythematous or purpuric patches with crusts on the anterior chest, knuckles, and elbows (Figures 2A,B) were observed. The three-phase bone scintigraphy revealed inflammation in the affected joints (Figure 2C). Skin biopsy of the anterior chest showed superficial perivascular inflammation (Figure 2D). Though the patient did not complain of muscle weakness and myalgia, magnetic resonance imaging (MRI) of the thigh showed contrast-enhancing asymmetric and patchy T2-hyperintensity in hip and thigh muscles (Figure 2E). The pathologic finding of muscle biopsy led to additional diagnosis of DM (Figure 2F).
Serial visual field tests and MRI findings of NMO in the patient. (A) The initial visual field (VF) test demonstrated the incomplete loss of the inferior and peripheral vision in the right eye, which partially improved after corticosteroid therapy (B). (C) Axial (a) and coronal (b) T1-weighted orbit MR images showed contrast enhancement in the right optic nerve at the back of the eye (arrow). (D) Sagittal MRI of the thoracic spine showed multifocal T2-hyperintensity (a) with patchy contrast enhancement (b). (E) VF test performed at the second attack of ON showed near-total blindness of the right eye, which was exacerbated to complete blindness a week after rituximab injection (F). (G) Follow-up orbit MRI showed the contrast-enhancing lesions (arrows) affecting the entire right optic nerve on the axial (a) and coronal (b) T1-weighted images. (H) Follow-up spine MRI after the second rituximab injection showed long segmental T2-hyperintensity (a) with diffuse enhancement (b) in the thoracic cord extending from T4 to T11 vertebral levels. OD, oculus dexter.
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F3
Visual field (VF) test showed altitudinal hemianopia involving the lower hemisphere (Figure 3A). Brain MRI showed retrobulbar neuritis of the right optic nerve (Figure 3C) without abnormality in the brain. Spine MRI showed multifocal contrast-enhancing T2-hyperintensity involving the thoracic spinal cord (Figure 3D). The visual acuity got better gradually (Figure 3B), but sensory disturbance did not. VF exam showed severe visual disturbance with periphery involvement (Figure 3E), and rituximab (IV, 1,000 mg each, 2 weeks apart) was decided to be administered to prevent further relapse of NMO. However, his VF defect was exacerbated after the first rituximab injection (Figure 3F), and orbit MRI demonstrated the relapse of optic neuritis (Figure 3G). Spine MRI showed longitudinally extensive transverse myelitis involving the thoracic cord (Figure 3H).
Serial chest CT findings and pulmonary functions of the patient. (A) Initial CT at the time of diagnosis of ILD showed perilobular consolidations and fibrosis in posterior aspects of the lower lobes, and forced vital capacity (FVC) was 3.05 L. (B) CT performed just before the rituximab injection showed the increased extent of fibrosis. However, the patient did not complain of respiratory symptoms including cough or dyspnea, and FVC was slightly improved by 4.6% compared to baseline. (C) CT performed immediately after the second rituximab injection showed an increased extent of fibrosis and perilobular consolidations. The patient developed mild dyspnea, and FVC declined by 11% from the latest one.
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F4
Computed tomography (CT) of the chest showed perilobular consolidations and fibrosis in the posterior aspect of both lower lungs (Figure 4A). Although pulmonary fibrosis seemed to be slightly progressed on the regular follow-up chest CT, his respiratory symptoms and FVC were rather improved (Figure 4B). FVC declined to 2.83 L (56% of the predicted) in PFT, and ILD was aggravated on chest CT (Figure 4C).