Subarachnoid hemorrhage and cerebral infarction in anti-glomerular basement membrane disease: a case report and literature review

Abstract

Anti-glomerular basement membrane (anti-GBM) disease is a rare autoimmune disorder characterized by rapidly progressive glomerulonephritis, with or without pulmonary hemorrhage. Central nervous system (CNS) involvement is exceedingly uncommon, and intracranial subarachnoid hemorrhage (SAH) has rarely been described in association with anti-GBM disease. We report a rare case of anti-GBM disease complicated by intracranial SAH and subsequent cerebral infarction. A 53-year-old woman presented with fever and headache and rapidly developed acute kidney injury with markedly elevated anti-GBM antibody titers. Renal biopsy confirmed anti-GBM disease. Despite treatment with plasma exchange and high-dose corticosteroids, renal function deteriorated, and the patient became dialysis-dependent. Rituximab was added to achieve serological control after an insufficient response to conventional therapy. During the clinical course, the patient developed a generalized seizure and was diagnosed with intracranial SAH, followed later by a subacute cerebral infarction. Cerebral angiography revealed no aneurysms or vascular malformations. Blood pressure had remained stable prior to the neurological event. Following intensive management, including continued plasma exchange, rituximab, corticosteroids, and strict blood pressure control, no neurological sequelae were observed. Anti-GBM antibody titers gradually declined, although renal function did not recover. This case illustrates a rare occurrence of intracranial subarachnoid hemorrhage as a central nervous system complication in anti-GBM disease and highlights the importance of careful neurological monitoring.

Introduction

Anti-glomerular basement membrane (anti-GBM) disease is a rare autoimmune disorder characterized by autoantibodies against the non-collagenous domain (NC1) of the α3 chain of type IV collagen. It typically presents as rapidly progressive glomerulonephritis with or without pulmonary hemorrhage. Delayed diagnosis and treatment can result in irreversible renal failure or death [1].

Central nervous system (CNS) involvement in anti-GBM disease is exceedingly rare, as the α3 chain of type IV collagen is primarily localized to renal and pulmonary basement membranes [1]. To date, 23 cases of anti-GBM disease with neuroimaging-confirmed CNS complications have been reported [2–23]. Most patients present with posterior reversible encephalopathy syndrome (PRES), whereas other reported manifestations include cerebral vasculitis, intracerebral hemorrhage, cerebral infarction, and thrombotic microangiopathy (TMA). However, to the best of our knowledge, no cases of intracranial subarachnoid hemorrhage (SAH) associated with anti-GBM disease have been reported. Although CNS complications have traditionally been attributed to factors such as hypertension, uremia, and treatment-related toxicity, immune-mediated mechanisms have also been discussed as a possible contributing factor. However, a direct causal relationship remains unestablished [9].

The standard therapy for anti-GBM disease consists of plasma exchange (PE), corticosteroids, and cyclophosphamide (CYC) [1]. However, the management of severe cases with a poor renal prognosis remains controversial. Rituximab (RTX), a monoclonal antibody targeting CD20-positive B cells, has been increasingly used as an alternative for patients with contraindications to CYC or as a second-line option in CYC-refractory cases. Several reports have suggested that the addition of RTX to standard therapy may be associated with a more rapid decline in anti-GBM antibody titers [24], although evidence for improved renal outcomes remains limited.

Herein, we report a rare case of anti-GBM disease complicated by intracranial SAH and subsequent subacute cerebral infarction, in which RTX was administered following an insufficient response to PE and corticosteroid therapy.

Case report

A 53-year-old woman with no significant medical or family history presented with a 2-week history of fever, headache, and upper respiratory symptoms. Laboratory tests revealed systemic inflammation (white blood cell [WBC] count 13,100/μL; C-reactive protein [CRP] 19.3 mg/dL) with preserved renal function (serum creatinine [sCr] 0.92 mg/dL). Empirical antibiotic therapy for a presumed respiratory tract infection was ineffective, and both the inflammation and renal function rapidly worsened. The patient was transferred to our hospital on day 1.

On admission, her vital signs were stable (blood pressure 102/63 mmHg, body temperature 36.2 °C). Physical and neurological examinations were unremarkable. Laboratory tests revealed acute renal dysfunction (sCr 2.70 mg/dL) and marked inflammation (WBC count 16,800/μL; CRP 25.55 mg/dL). Urinalysis revealed proteinuria (1.98 g/gCr), gross hematuria, and epithelial and granular casts. Serological studies showed elevated complement component 3 (C3, 188.9 mg/dL), whereas complement component 4 (C4), immunoglobulins, antinuclear antibody, rheumatoid factor, myeloperoxidase (MPO), and proteinase 3 (PR3)-antineutrophil cytoplasmic antibodies (ANCA), and viral hepatitis markers were all negative. Anti-GBM antibody titers exceeded the upper limit of detection (> 350 U/mL; normal < 2.9 U/mL). A summary of the laboratory and urinalysis results is presented in Table 1.

Table 1.

Laboratory data on admission

Hematological values			Serum biochemistry			Immunological studies
White blood cell count	16,800	/μL	Total protein	6.2	g/dL	CRP	25.55	mg/dL
Neutrophils	84.6	%	Albumin	2.5	g/dL	C3	188.9	mg/dL (65–135)
Lymphocytes	6.1	%	AST	12	U/L	C4	34.8	mg/dL (13–35)
Monocytes	8.6	%	ALT	15	U/L	IgG	1,006	mg/dL (870–1,700)
Eosinophils	0.4	%	LDH	241	U/L	IgA	242	mg/dL (110–410)
Red blood cell count	3.10 × 104	/μL	BUN	22.6	mg/dL	IgM	112	mg/dL (35–220)
Hemoglobin	9.2	g/dL	Creatinine	2.7	mg/dL	Antinuclear antibody	( −)
Hematocrit	27.5	%	Sodium	136	mEq/L	Rheumatoid factor	9.9	IU/mL (< 15)
Platelet count	42.2 × 104	/μL	Potassium	3.7	mEq/L	Anti-dsDNA antibody	1.6	IU/mL (< 12)
			Chloride	104	mEq/L	Anti-SS-A antibody	0.3	U/mL (< 10)
Urinalysis			Glucose	118	mg/dL	MPO-ANCA	0.2	U/mL (< 3.4)
Protein	(2 +)		HbA1c	5.1	%	PR3-ANCA	0.1	U/mL (< 3.4)
Glucose	( −)					Anti-GBM antibody	> 350	U/mL (< 2.9)
Occult blood	(3 +)		Coagulation tests
Red blood cells	> 100	/HPF	PT-INR	1.37		Infection-related tests
White blood cells	10–19	/HPF	APTT	43.8	S	HBs antigen	( −)
Epithelial casts	(1 +)					HBs antibody	( −)
Granular casts	(1 +)					HCV antibody	( −)
						TPHA	( −)
Urinary chemistry						RPR	( −)
UP/UCr	1.98	g/gCr				T-SPOT	( −)

Chest radiography and thoracoabdominal computed tomography (CT) revealed no evidence of alveolar hemorrhage. Transthoracic echocardiography and lower extremity ultrasonography performed on days 4 and 17 revealed no evidence of intracardiac thrombi or deep vein thrombosis. A renal biopsy performed on day 3 revealed 40 glomeruli, including one globally sclerotic glomerulus. Periodic acid–Schiff (PAS) and hematoxylin and eosin (H&E) staining revealed cellular crescents, fibrinoid necrosis, or both, in 34 glomeruli. Immunofluorescence staining demonstrated homogeneous linear deposition of immunoglobulin G and C3 along the glomerular capillary walls (Fig. 1), confirming the diagnosis of anti-GBM disease.

Fig. 1.

Renal biopsy findings. A Hematoxylin and eosin (H&E) staining showing fibrinoid necrosis (black dotted circle) (× 200). B Periodic acid–Schiff (PAS) staining demonstrating cellular crescent formation (× 200). C, D Immunofluorescence staining for complement component 3 (C) and IgG (D) showing homogeneous linear deposition along the glomerular capillary walls

Intravenous methylprednisolone pulse therapy (1,000 mg/day for 3 days) was initiated on day 3, followed by oral prednisolone 40 mg/day (0.6 mg/kg). PE was initiated on day 4 and performed three times per week. Fresh frozen plasma (FFP) was used as the replacement fluid, with 32 units exchanged during the first four sessions and 48 units per session thereafter. Despite these treatments, renal function further deteriorated, and hemodialysis (HD) was initiated on day 7. After the third PE session on day 9, the anti-GBM antibody titers remained above the upper limit of detection. On day 10, the inflammatory marker levels increased again (WBC count 19,600/μL; CRP 24.99 mg/dL). Therefore, a second course of intravenous methylprednisolone (1,000 mg/day for 3 days) was administered on day 11. On day 15, RTX at 375 mg/m² (630 mg) was added to the ongoing PE and corticosteroid regimens to suppress excessive anti-GBM antibody production. To avoid overlapping treatment-related adverse events and to minimize potential removal by PE, RTX was administered on the day following PE, maintaining an interval of at least 24 h before subsequent PE sessions. Due to concerns about infection under intense immunosuppression, empirical antimicrobial and antiviral therapies with piperacillin/tazobactam, vancomycin, and ganciclovir were administered. From admission until the onset of the neurological event, the patient’s systolic blood pressure remained stable, ranging between 110 and 140 mmHg under routine monitoring.

On day 18, the patient was found unconscious with fecal incontinence, followed by a generalized tonic–clonic seizure. Her blood pressure was markedly elevated (194/126 mmHg). Inflammatory markers remained elevated (WBC count 51,700/μL; CRP 8.36 mg/dL), and the anti-GBM antibody titer persisted above the upper detection limit, whereas ANCA levels remained persistently negative. Head CT revealed high-attenuation areas along the cortical sulci of the left temporal lobe, consistent with a cortical SAH (Fig. 2). The patient was intubated for airway protection, and contrast-enhanced CT and cerebral angiography revealed no aneurysms or vascular malformations. Intravenous nicardipine for blood pressure control, levetiracetam (1,000 mg/day) for seizure prophylaxis, and propofol for sedation were administered. The oral corticosteroids were switched to intravenous prednisolone (60 mg/day).

Fig. 2.

Neuroimaging findings of the brain on day 15. A–D Non-contrast head computed tomography (CT) showing high-attenuation areas along the cortical sulci of the left temporal lobe, consistent with a cortical subarachnoid hemorrhage (SAH) (arrowheads). An arachnoid cyst is also observed in the posterior cranial fossa (black dotted circle). E, F CT angiography showing no evidence of an intracranial aneurysm or an arteriovenous malformation. G Conventional cerebral angiography demonstrating that no vascular lesions were responsible for the SAH

Follow-up cerebral angiography performed on day 21 revealed no new bleeding or aneurysmal changes. After stabilization, the patient was extubated, and PE was resumed on day 22 and continued thereafter. Following the onset of SAH, FFP replacement was continued to maintain coagulation capacity. RTX therapy was continued under close monitoring, with four RTX doses and 22 PE sessions administered throughout the patient’s clinical course. On day 36, follow-up brain magnetic resonance imaging (MRI) revealed a high-intensity lesion in the left temporal lobe on diffusion-weighted and fluid-attenuated inversion recovery (FLAIR) sequences, consistent with a subacute cerebral infarction (Fig. 3). No neurological deficits were observed. Strict blood pressure control was continued, and an MRI on day 43 confirmed the absence of a new infarction or recurrent SAH. Antiphospholipid antibodies measured after the onset of cerebral infarction were negative.

Fig. 3.

Serial brain magnetic resonance imaging findings. On day 36, diffusion-weighted imaging (DWI) and fluid-attenuated inversion recovery (FLAIR) sequences show high-intensity signals, predominantly in the cortical regions of the left frontal, parietal, and temporal lobes, consistent with a diagnosis of subacute cerebral infarction (arrowheads). No new subarachnoid hemorrhage (SAH) was observed. Follow-up magnetic resonance imaging on days 43 and 57 demonstrated no evidence of a new cerebral infarction or SAH

The patient’s renal function did not recover, and maintenance HD was initiated. The anti-GBM antibody titer gradually decreased, reaching 83.0 U/mL on day 51. PE was discontinued on day 53, and the antibody titers remained stable thereafter (85.8 U/mL on day 60). The patient was discharged on day 64 without any neurological sequelae. During follow-up, oral corticosteroids were continued with periodic RTX infusion. The antibody titers further dropped to 72.4 U/mL on day 73 and 2.9 U/mL on day 269 without relapse. The patient’s overall clinical course is summarized in Fig. 4.

Fig. 4.

Patient’s clinical course. CRP, C-reactive protein; CT, computed tomography; GBM, glomerular basement membrane; HD, hemodialysis; mPSL, methylprednisolone; MRI, magnetic resonance imaging; PE, plasma exchange; PSL, prednisolone; RTX, rituximab; SAH, subarachnoid hemorrhage

Discussion

This case provides two clinically relevant observations. First, intracranial SAH, although exceedingly rare, was observed during the clinical course of anti-GBM disease in this case. Second, the decline in anti-GBM antibody titers observed after RTX administration may suggest a potential role for RTX in serological control when conventional therapy is insufficient, although its contribution remains uncertain.

To date, 23 cases of anti-GBM disease with neuroimaging-confirmed CNS complications have been reported, and their clinical features, together with those of the present case, are summarized in Table 2 [2–23]. The reported ages ranged from 14 to 77 years. Hypertension was documented in most cases with available blood pressure data, whereas pulmonary hemorrhage was variably present. Among patients with available ANCA data, only a small proportion were ANCA-positive, which is lower than expected for double-positive anti-GBM disease [25]. This finding may reflect publication bias, as CNS involvement is relatively common in ANCA-associated vasculitis and may therefore be less frequently reported in such overlapping conditions [26]. Renal outcomes were generally poor, with the majority of patients progressing to end-stage kidney disease requiring renal replacement therapy. In many reports, anti-GBM antibody titers were markedly elevated, often exceeding assay detection limits, although direct comparisons are limited by differences in assay methodologies.

Table 2.

Previously reported cases of anti-GBM disease with central nervous system complications

No	References	Age / Sex	CNS complication			Anti-GBM antibody titera	RRT	HT	PH	ANCA	Treatment of anti-GBM disease
			Type	Timing of onset	Outcome						Before CNS complication	After CNS complication
1	Lahmer et al. [2]	23 / M	PRES	At presentation	No neurological sequelae	> 200 (U/mL; N/A)	mHD → KTx	( +)	( +)	N/A	No immunosuppressive therapy	CYC, PE, (PSL, TAC, MMF)d
2	Camara-Lemarroy et al. [3]	22 / F	PRES	During remission induction	No neurological sequelae	169 (U/mL; < 20)	mHD	( +)	( +)	(–)	mPSL pulse, CYC, RTX, PE	Immunosuppressive therapy continued
3	Maël et al. [4]	27 / M	PRES	During remission induction	No neurological sequelae	N/A	mHD	( +)	N/A	N/A	PSL, CYC, PE	N/A
4	Han et al. (Case 2) [5]	77 / F	PRES or uremic encephalopathy	During remission induction	No neurological sequelae	232.37 (RU/mL; N/A)	mHD	( +)	(–)	(–)	PSL, MMF, PE	PSL, PE
5	Ozkok et al. [6]	22 / F	PRES	During remission induction; after first mPSL pulse	No neurological sequelae	N/A	mHD	( +)	( +)	N/A	mPSL pulse	mPSL pulse, PSL, CYC, PE
6	Torigoe et al. [7]	48 / F	PRES, APS, TMA	During remission induction; hospital day 8	No further seizures	700 (U/mL; < 7.0)	mHD	( +)	( +)	(–)	mPSL pulse, PSL, PE	mPSL pulse, PSL, CYC, PE
7	Nisar et al. [8]	29 / F	PRES	During remission induction; hospital day 11, 2 days after CYC	No neurological sequelae	N/A	N/A	(–)	N/A	p-ANCA ( +)	mPSL pulse, PSL, CYC, PE	PSL
8	Han et al. (Case 1) [5]	40 / F	PRES	During remission induction; hospital day 12, 2 days after CYC	No neurological sequelae	N/A	mHD	( +)	( +)	(–)	mPSL pulse, PSL, CYC, PE	PSL, PE
9	Taniguchi et al. [9]	33 / F	PRES	During remission induction; hospital day 15, 8 days after CYC	No further seizures	350 (U/mL; N/A)	Dialysis discontinued	( +)	(–)	(–)	mPSL pulse, PSL, CYC, PE	PSL, CYC, RTX, PE
10	Yahata et al. [10]	47 / M	PRES	During remission induction; hospital day 17	No neurological sequelae	57 (EU; N/A)	mHD	( +)	(–)	(–)	mPSL pulse, PSL, PE	mPSL pulse, PSL, CYC, PE
11	Tsuneyoshi et al. [11]	71 / F	PRES, cerebral hemorrhage	During remission induction; hospital day 21	No neurological sequelae	457 (U/mL; N/A)	mHD	( +)	( +)	(–)	mPSL pulse, PSL, PE	mPSL pulse, PSL, CYC
12	Momose et al. [12]	54 / M	PRES, TMA, cerebral hemorrhage	During remission induction; hospital day 48	Able to walk with a cane	230 (EU; N/A)	mHD	( +)	(–)	(–)	mPSL pulse, PSL, PE	PSL, PE
13	Ge et al. [13]	24 / M	PRES	During remission induction; hospital day 56, 2 days after CYC	Seizures controlled	N/A	mHD	( +)	(–)	(–)	mPSL pulse, PSL, CYC, PE	PSL; CYC discontinued
14	Uematsu et al. [14]	53 / F	PRES	During remission induction; hospital week 13, 9 weeks after RTX	N/A	1,170 (U/mL; N/A)	mHDc	( +)	(–)	(–)	mPSL pulse, PSL, RTX, PE	PSL
15	Abenza-Abildua et al. [15]	27 / M	PRES	1 month after remission induction	No neurological sequelae	N/A	mHD	( +)	N/A	N/A	PSL, CYC,	PSL, RTX; CYC discontinued
16	Cha et al. [16]	36 / F	PRES	3 months after remission induction	No neurological sequelae, no further seizures	> 600 (U/mL; N/A)	mHD	( +)	(–)	(–)	mPSL pulse, mPSL, CYC, PE	mPSL; CYC discontinued
17	Gutiérrez-Sánchez et al. [17]	22 / F	PRES	4 months after remission induction	No further seizures	N/A	mHD	( +)	(–)	(–)	mPSL pulse, PSL, CYC, PE	All immunosuppressive agents had been discontinued
18	Preul et al. [18]	21 / M	PRES or CNS vasculitis	5 months after remission induction	No neurological sequelae	200 (U/mL; < 10)	PD	( +)	( +)	(–)	CYC	CYC, PE
19	Kim et al. [19]	34 / M	CNS vasculitis	At presentation	No neurological sequelae	(–)b	Normal renal function	N/A	( +)	(–)	No immunosuppressive therapy	mPSL pulse, PSL, PE
20	Rydel et al. [20]	18 / M	CNS vasculitis, cerebral infarction	During remission induction; hospital day 10	Able to attend school full-time	1,780 (U/mL; < 10)	PD → KTx	(–)	( +)	(–)	mPSL pulse, PSL, CYC, PE	mPSL pulse, PSL, CYC (dose increased), PE
21	Gittins et al. [21]	14 / F	CNS vasculitis	During remission induction; hospital day 29	No neurological sequelae, no further seizures	400 (U/mL; < 20)	mHD	( +)	( +)	(–)	PSL, CYC, PE	PSL, CYC (frequency increased), PE
22	Taieb et al. [22]	62 / F	Spinal subarachnoid hematoma, cerebral infarction, CNS vasculitis	During remission induction; treatment day 4	Death	80 (U/mL; < 20)	HD; in-hospital death	(–)	(–)	p-ANCA 100 U/mL	mPSL pulse, PSL, CYC, PE	PSL, CYC, RTX, PE
23	Watanabe et al. [23]	61 / F	Cerebral infarction, TTP	During remission induction; hospital day 16	Death	920 (EU; N/A)	HD; in-hospital death	(–)	(–)	MPO-ANCA 66 U/mL	mPSL pulse, PSL, PE	PSL, PEe
	Present case	53 / F	SAH, subacute cerebral infarction	During remission induction; hospital day 17, 3 days after RTX	No neurological sequelae, no further seizures	> 350 (U/mL; < 2.9)	mHD	( +)	(–)	(–)	mPSL pulse, PSL, RTX, PE	PSL, RTX, PE

ANCA antineutrophil cytoplasmic antibodies, APS antiphospholipid syndrome, CNS central nervous system, CYC cyclophosphamide, GBM glomerular basement membrane, HD hemodialysis, HT hypertension, KTx kidney transplantation, mHD maintenance hemodialysis, mPSL methylprednisolone, MMF mycophenolate mofetil, MPO myeloperoxidase, N/A not available, PD peritoneal dialysis, PE plasma exchange, PH pulmonary hemorrhage, PRES posterior reversible encephalopathy syndrome, PSL prednisolone, RTX rituximab, RRT renal replacement therapy, SAH subarachnoid hemorrhage, TAC tacrolimus, TMA thrombotic microangiopathy, TTP thrombotic thrombocytopenic purpura

^aAnti-GBM antibody titers are reported as provided in each reference. Units varied among studies (U/mL, RU/mL, or EU), and reference ranges are shown as originally reported

^bAnti-GBM antibody was negative; diagnosis was confirmed by renal biopsy showing linear IgG deposition

^cDialysis was discontinued at discharge but maintenance hemodialysis was resumed 5 weeks later

^dAdministered as part of the post-transplantation immunosuppressive regimen

^eAdditional PE sessions were performed for concomitant TTP

With respect to neurological manifestations, PRES was the most frequently reported phenotype, followed by cerebral vasculitis, cerebral infarction, intracerebral hemorrhage, and spinal subarachnoid hematoma. Intracranial SAH has not been described in previous reports of anti-GBM disease, making the present case a rare manifestation within the spectrum of CNS involvement. The timing of CNS complications varied widely, occurring at disease onset, during induction therapy, or several months after diagnosis. Importantly, reported management strategies differed considerably, reflecting the difficulty in distinguishing treatment-related toxicity from disease progression. In some cases, CNS manifestations were interpreted as disease activity, leading to intensification of immunosuppressive therapy, whereas in others they were considered treatment-related adverse events, prompting discontinuation or modification of anti-GBM disease–directed therapy. Although neurological outcomes were favorable in most cases, fatal outcomes were reported in a small number of patients, underscoring the potential severity of CNS involvement.

In the present case, the clinical features, including marked hypertension at onset, uremia, and generalized seizures, raised the possibility of PRES. The subsequent development of subacute cerebral infarction may reflect the progression of PRES-associated vasogenic edema to irreversible ischemia. Hemorrhagic manifestations, including cortical SAH, have been reported in PRES, although they are less common [27]. Therefore, PRES may have contributed to the sequence of neurological events in this case, although the absence of an early MRI precludes a definitive diagnosis. At the onset of the SAH, the patient’s blood pressure was markedly elevated immediately prior to a scheduled hemodialysis session, and therefore, the contribution of volume overload cannot be excluded. However, the systolic blood pressure had remained stable, including before the hemodialysis sessions, throughout the clinical course before the SAH onset, suggesting that volume overload was unlikely to be the sole contributing factor.

Regarding the mechanism of the delayed cerebral infarction, several possibilities should be considered. Although delayed vasospasm cannot be excluded, the systolic blood pressure was maintained at ≥ 110 mmHg throughout hospitalization, including during plasma exchange and hemodialysis sessions, making significant hypoperfusion less likely. In addition, no evidence of deep vein thrombosis or intracardiac thrombus was detected on ultrasonography or echocardiography, and antiphospholipid antibodies were negative, suggesting that thromboembolic mechanisms were unlikely.

The mechanisms underlying CNS complications in anti-GBM disease remain incompletely understood. In addition to secondary vascular injury related to hypertension, uremia, or treatment-related factors, immune-mediated vascular damage has been proposed. Certain anti-GBM antibodies exhibit cross-reactivity with other type IV collagen chains, including α1 and α2, which are expressed in cerebral vascular basement membranes [28, 29]. Patients with severe renal impairment may develop broader antigenic reactivity, potentially increasing susceptibility to vascular injury. Indeed, one previous report described histopathologically confirmed CNS vasculitis in anti-GBM disease with an antibody titer of 1,780 U/mL requiring renal replacement therapy [20], suggesting that antibody-mediated cerebral vascular injury is biologically plausible. Nevertheless, such cases are exceedingly rare, and direct evidence supporting a causal relationship between anti-GBM antibodies and CNS vascular damage remains limited. Accordingly, the observed association may reflect overall disease severity rather than a specific pathogenic mechanism.

The 2021 KDIGO guidelines suggest RTX as a potential therapeutic option for refractory anti-GBM disease, while emphasizing the need for studies directly comparing RTX with CYC [30]. Several studies have reported a more rapid decline in anti-GBM antibody titers in patients receiving RTX in addition to standard therapy [24, 31]; however, these findings are based on case series or retrospective analyses, and the level of evidence remains limited.

In the present case, CYC was not initiated because infection could not be excluded, and the patient rapidly became dialysis-dependent, making renal recovery unlikely. RTX was introduced primarily to achieve serological control after an insufficient response to plasma exchange and corticosteroids. RTX was administered on the day following PE to avoid overlapping treatment-related adverse events and to minimize potential drug removal, maintaining an interval of at least 24 h before subsequent PE sessions. PE is known to remove circulating RTX; however, previous pharmacokinetic studies suggest that B-cell depletion may still be achieved when PE is performed 24–72 h after RTX administration [32]. Peripheral B-cell counts were not monitored in this case; therefore, the degree of B-cell depletion could not be confirmed.

Following RTX administration, anti-GBM antibody titers and inflammatory markers gradually declined, and no rebound in antibody levels was observed after discontinuation of PE. However, the contribution of RTX to these changes remains uncertain, as multiple therapies were administered concurrently. Given the limited evidence base, individualized treatment decisions remain essential in severe anti-GBM disease complicated by CNS involvement.

In conclusion, this case represents a rare occurrence of intracranial SAH during the clinical course of anti-GBM disease. Although a direct causal relationship remains unclear, careful neurological monitoring may be warranted in patients with severe disease.

RTX may have a potential role as a therapeutic option for serological control in selected patients when conventional therapy is insufficient, although further evidence is needed to clarify its optimal role.

Declarations

Conflict of interest

The authors declare that they have no conflicts of interest.

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors.

Informed consent

Written informed consent was obtained from the patient for publication of this case report and any accompanying images.