Immunoglobulins (IG) are essential in the treatment of autoimmune diseases [1], although their adverse effects may force treatment withdrawal in a significant number of cases [2]. While the anti-inflammatory and immunomodulatory effects of high-dose IG are well-documented across multiple approved and off-label indications [3], management of its side effects remains a challenge. We present the case of a patient with immune‑mediated necrotizing myopathy (IMNM) whose refractory headache after IG infusion resolved with a preventive approach based on the chronology of symptoms.

A 45‑year‑old woman with IMNM and a 5‑year history of chronic headache, which began after high‑dose corticosteroid therapy. Her medical history included a stable left temporal multinodular and vacuolating neuronal tumor (MVNT). Recent radiologic characterizations of MVNT suggest these are typically benign, non-progressive lesions [4]; in our patient, follow-up brain MRI during acute headache episodes confirmed the stability of the lesion with no perilesional edema, ruling it out as the trigger for the acute exacerbations.

The patient was refractory to multiple therapeutic lines for her headache (amitriptyline, triptans, and valproate, among others). Due to persistent inflammatory activity of her IMNM, monthly IG treatment was initiated (2 g/kg). She initially received Flebogamma DIF®, which intensified her headache to a VAS 10, requiring hospitalization and sedation. Treatment was switched to Privigen®, but severe headache persisted despite better gastrointestinal tolerance. The patient identified a specific pattern: symptoms peaked on day +8 and lasted until day +18, accompanied by slightly elevated blood pressure and mild ankle edema.

Based on the clinical suspicion of transient cerebral edema due to hyperviscosity or volume overload—a mechanism also implicated in more severe conditions like posterior reversible encephalopathy syndrome (PRES) [5]—we opted for a short course of loop diuretics. Oral furosemide 80 mg/day was administered from day +2 to day +7 of the cycle. From the first cycle using this regimen, the patient did not experience IG‑related headache again. Muscle cramps occurred on day +5 but resolved with oral potassium gluconate (20 mEq/day).

The repeated clinical response suggests that preventive treatment with diuretics avoided the onset of headache. A key differential diagnosis is IgIV-associated aseptic meningitis, which typically presents with fever and nuchal rigidity [6]. However, our patient lacked these signs, pointing instead toward a hemodynamic mechanism. Although the 2023 AANEM consensus highlights the importance of IG in neuromuscular disorders [7], it also emphasizes that side effects significantly impact quality of life.

A limitation of this report is the lack of objective intracranial pressure (ICP) measurements during the peak headache phase. However, our hypothesis of transiently increased ICP secondary to cerebral edema is supported by the therapeutic success. Implementing therapeutic strategies that make these effects more tolerable ensures patient well‑being and guarantees the continuity of irreplaceable treatments.