Myeloperoxidase-antineutrophil cytoplasmic antibody-associated vasculitis with headache and kidney involvement at presentation and with arthralgia at relapse: A case report

Abstract

BACKGROUND

Patients with proteinase 3-antineutrophil cytoplasmic antibody associated vasculitis (AAV) experience different manifestations at the initial onset and relapse. However, such cases of different initial and relapse manifestations have not been reported in myeloperoxidase (MPO)-AAV patients.

CASE SUMMARY

A 52-year-old woman was admitted to our hospital because of headache. Laboratory findings indicated nephrotic range proteinuria and microscopic hematuria, serum creatinine of 243 μmol/L, anti-MPO antibody titer of > 400 RU/mL, and positive perinuclearantineutrophil cytoplasmic antibody. Renal biopsy showed pauci-immune crescentic glomerulonephritis. The cerebrospinal fluid examination and brain magnetic resonance imaging did not show any abnormality. Therefore, MPO-AAV was diagnosed. Corticosteroids, plasmapheresis, and cyclophosphamide as induction therapy and mycophenolate mofetil (MMF) as maintenance therapy were administered. The patient’s headache disappeared; serum creatinine returned to normal; complete remission of microscopic hematuria and proteinuria was observed. Anti-MPO antibody titer reached normal limits after immunosuppressive treatment. Twenty-five months after stopping the immunosuppressive treatment, the patient relapsed with arthralgia, without neurological or renal involvement. The patient’s arthralgia improved after treatment with prednisone and MMF.

CONCLUSION

We have reported a rare case of MPO-AAV who initially presented with headache and kidney involvement. However, relapse presented with only arthralgia, which was completely different from the initial manifestations. This case suggests that AAV relapse should be highly suspected in MPO-AAV patients after remission, when clinical manifestations at relapse are different from those at onset. Prednisone and MMF may provide a good choice for refractory arthralgia during relapse in MPO-AAV patients.

Key Words: Antineutrophil cytoplasmic antibody associated vasculitis, Headache, Kidney, Arthralgia, Relapse, Case report

Core Tip: We report a rare case of myeloperoxidase (MPO)-antineutrophil cytoplasmic antibody-associated vasculitis (AAV) who initially presented with headache and kidney involvement. However, relapse presented with only arthralgia, which was completely different from the initial manifestations. This case suggests that AAV relapse should be highly suspected in MPO-AAV patients after remission, when clinical manifestations at relapse are different from those at onset. Prednisone and mycophenolate mofetil may provide a good choice for refractory arthralgia during relapse in MPO-AAV patients.

INTRODUCTION

Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a group of disorders characterized by necrotizing vasculitis in small- and medium-sized vessels with few or no immune deposits[1]. AAV may affect one or several organ systems. Initial AAV onset is most common in the kidney (72.3%), followed by the lungs (45%) and the ear, nose, and throat (29.7%)[2,3]. However, only 4.9%-20% of AAV patients initially present with neurological symptoms, of which peripheral neuropathy is predominant[4,5]. A total of 22.3%-53.5% of AAV patients who achieved remission experienced relapses[3,6-8]. The kidney (63.1%) and lung (47.4%) are the two most common involved organs at relapse, whereas joint involvement is rare (7%-21%)[8,9]. Among AAV patients, 72.4% had kidney involvement at the initial onset and at relapse[10]. In patients with proteinase 3 (PR3)-AAV, different organs are involved at the initial onset and relapse, whereas in patients with myeloperoxidase (MPO)-AAV, the same organ is involved at both instances[8,10]. Here, we report the rare case of an MPO-AAV patient, who presented with headache and kidney involvement at initial onset and developed arthralgia at relapse. Our case showed completely different clinical manifestations at the initial onset and relapse, which has not been reported previously.

CASE PRESENTATION

Chief complaints

A 52-year-old female patient had headache for 2 mo.

History of present illness

A 52-year-old female patient was admitted to our hospital in December 2014, because of headache for 2 mo without obvious predisposing causes.

Physical examination

On admission, the patient’s temperature was 37.2 °C, blood pressure was 140/90 mmHg, and her neurological examination was normal.

Laboratory examinations

The patient’s laboratory test results were as follows: White blood cell count 5.81 × 10⁹/L (normal range 3.5-9.5 × 10⁹/L), hemoglobin level 74 g/L (115-150 g/L), and platelet count 204 × 10⁹/L (125-350 × 10⁹/L). The patient’s microscopic hematuria was 10-15 red blood cells (RBCs)/high power field (HPF); her 24-h urinary protein level was 3273 mg, and serum creatinine level was 243 μmol/L. The erythrocyte sedimentation rate was 26 mm/h (normal range 0-20 mm/h), and hypersensitive C-reactive protein level (CRP) was 61.6 mg/L (normal range 0-8 mg/L). The immunoglobulin (Ig)G, IgA, and IgM levels were normal. Complement (C)3 and C4 levels were normal. The antinuclear antibody test was negative. Rheumatoid factor level was 20.1 IU/mL (0-20 IU/mL). Serum anti-MPO antibody titer was > 400 RU/mL (normal range < 20 RU/mL), and PR3-ANCA was negative. Cerebrospinal fluid (CSF) examination revealed normal pressure, and total protein levels and cell count were within normal limits. A cytological examination for malignant cells was negative in the serum as well as in the CSF. Renal pathology revealed crescentic necrotizing glomerulonephritis on light microscopy, and no specific findings were observed on immunofluorescence microscopy and electron microscopy (Figure 1).

Figure 1 Kidney pathology showing crescentic glomerulonephritis and focal fibrinoid necrosis under a light microscope. A: Hematoxylin and eosin staining, 400 × magnification; B: Periodic acid-Schiff staining, 400 × magnification; C: Periodic Schiff-methenamine silver staining, 400 × magnification; D: Masson trichrome staining, 400 × magnification.

Imaging examinations

Magnetic resonance imaging (MRI) and magnetic resonance angiography (MRA) scans of the brain showed no remarkable findings. No evidence of intracranial infection or cerebrovascular disease was observed.

FINAL DIAGNOSIS

The patient was diagnosed as having MPO-AAV.

TREATMENT

Corticosteroids in combination with cyclophosphamide and plasmapheresis as induction treatment were administered. The patient was treated with 500 mg intravenous methylprednisolone for 3 d, followed by 40 mg oral prednisone per day and 600 mg cyclophosphamide for 2 d. Ten plasma exchanges were performed every 2 d. Her symptoms gradually improved, and serum creatinine level was reduced to 129 μmol/L. The patient was discharged and was followed every month for 1 year.

OUTCOME AND FOLLOW-UP

After discharge, oral prednisone was slowly tapered. Intravenous cyclophosphamide was administered 600 mg every 2 wk. Four months after discharge, the patient’s headache resolved. Her serum creatinine was reduced to 110 μmol/L. Urine analysis showed 0-2 RBCs/HPF, 24-h urinary protein decreased to 1825 mg, and anti-MPO antibody titer dropped to 19.5 RU/mL. Five months after discharge, intravenous cyclophosphamide (cumulative dose of 10.8 g) was discontinued, and then, according to the KDIGO 2021 guideline, oral mycophenolate mofetil (MMF) 0.5 g was administered twice daily. In February 2019, her serum creatinine was further reduced to 74 μmol/L, 24-h urinary protein was reduced to 594 mg, microscopic hematuria disappeared, anti-MPO antibody titer decreased to 13.40 RU/mL, and the perinuclear antineutrophil cytoplasmic antibody (pANCA) test was negative. Based on these findings, oral prednisone and MMF were stopped. The patient was regularly followed every 1 to 2 mo.

In December 2019, the patient’s anti-MPO antibody titer increased to 21.9 RU/mL, and serum creatinine level increased to 118 μmol/L, but no microscopic hematuria or elevations in CRP levels were observed. The patient did not have any symptoms.

In March 2021, the patient complained of arthralgia. Laboratory test results were as follows: Serum creatinine, urinary protein, and CRP levels were 112 μmol/L, 81 mg/24 h, and 3.24 mg/L, respectively, with no microscopic hematuria. Serum anti-MPO antibody levels were > 400 RU/mL, and the patient’s pANCA test was positive. Serum anti-cyclic citrullinated peptide antibody level and hand X-ray scan were normal. High levels of anti-MPO antibody and positive pANCA indicated recurrence of MPO-AAV that presented as arthralgia, without CNS and kidney involvement. The patient was treated with 30 mg oral prednisolone per day and 600 mg of intravenous rituximab that was administered once one week for four times (375 mg/m²). Even after 3 mo, the patient’s arthralgia did not improve. The anti-MPO antibody titer was still > 400 RU/mL, and pANCA was positive. Oral prednisone was gradually tapered, and MMF (0.5 g twice a day) was administered since June 2021. With this treatment, the arthralgia gradually improved. The patient’s anti-MPO antibody titer decreased gradually. Clinical course and trends for anti-MPO antibody titer, serum creatinine level, and 24-h urinary protein level in our patient are shown in Figure 2.

Figure 2 Clinical course, proteinuria, serum creatinine, and anti-myeloperoxidase antibody level in our patient. A: Clinical course and laboratory test findings in our patient; B: Trends of 24-h urinary protein, serum creatinine, and anti-myeloperoxidase antibody titer. GC: Glucocorticoids; PE: Plasma exchange; CTX: Cyclophosphamide; MMF: Mycophenolate mofetil; RTX: Rituximab; Scr: Serum creatinine; UP: 24-h urinary protein or urinary protein; Ab: Antibody; MPO: Myeloperoxidase.

DISCUSSION

In this paper, we describe a 52-year-old woman with MPO-AAV, who presented with CNS (headache) and kidney involvement at initial onset. After the initial and maintenance immunosuppressive treatment, her headache disappeared and renal function recovered. Twenty-five months after stopping immunosuppressive therapy, arthralgia was observed at relapse without nervous system and renal involvement. The patient received prednisone and MMF, with which her arthralgia completely resolved. The manifestation of MPO-AAV at relapse was completely different from that at onset, which is quite rare.

Headache in AAV patients mainly occurs with meningeal or pituitary involvement and cerebral vascular inflammation[11,12]. In our case, brain MRI and MRA scans and CSF examination showed no abnormality. Further, the patient’s headache improved after immunosuppressive therapy. No other cause of headache could be identified. Therefore, the headache was considered to be related to AAV. A previous study reported a Japanese patient with AAV who also initially presented with headache, but this case was different from ours in that the patient presented with analgesia at all four extremities but had no kidney involvement[13].

The same organ is reported to be involved at initial onset and relapse in patients with AAV[8,10], and MPO-AAV cases with involvement in different organs at initial onset and relapse have been not reported. Our MPO-AAV patient presented with headache and kidney injury at initial onset and arthralgia at relapse, making this a rare case in the literature. Therefore, AAV relapse should be highly suspected when patients with MPO-AAV who have achieved remission present with manifestations in different organ systems.

Combined treatment with prednisone and rituximab in the initial and relapse phases in AAV patients with arthralgias shows good response[14-17]. However, when no improvement is observed within 4 to 6 wk[1], an alternative treatment scheme is needed. Even after 3 mo of prednisone and rituximab therapy, our patient showed a poor response during relapse. Therefore, a combination of prednisone and MMF was administered. After 6 mo, the patient’s arthralgia resolved. Prednisone combined with MMF may be a good choice for patients with recurrent AAV with refractory arthralgia.

After the induction and maintenance therapy, the patient’s serum creatinine reached normal levels, and her serum creatinine levels increased slightly 10 mo after stopping the immunosuppressive treatment. The patient had no microscopic hematuria and proteinuria, suggesting that her renal function deterioration was not associated with AAV recurrence. Repeated renal biopsy and pathological analysis were required. However, the patient refused to undergo these analyses.

CONCLUSION

In conclusion, we present the rare case of a patient with MPO-AAV who initially presented with headache and kidney involvement and later presented with only arthralgia at relapse. This case suggests that AAV relapse should be highly suspected in MPO-AAV patients after remission, when clinical manifestations at relapse are different from those at onset. Prednisone and MMF may provide a good choice for refractory arthralgia during relapse in MPO-AAV patients.