PO:21:021 | The eyes tell the story: a clinical case of Rosah syndrome

Nicolò Sabbion¹, Sofia Vitale¹, Claudia Balicchia¹, Barbara Troise¹, Francesca Mascia¹, Eleonora Bassanello², Jacopo Croce², Federica Maiolini², Filippo Mazzi², Elisa Tinazzi², Francesca Bosello¹, Simonetta Friso¹, Lucia De Franceschi¹ | ¹Università degli Studi di Verona; ²Azienda Ospedaliera Universitaria Integrata, Verona, Italy

Background. ROSAH syndrome is a rare autoinflammatory disease with autosomal dominant inheritance caused by gain-of-function missense mutations in the ALPK1 gene on chromosome 4. This leads to hyperactivation of the NF-κB signaling pathway and chronic cytokine-mediated inflammation (IL-1, IL-6, and TNF-alpha). ROSAH is an acronym for the following clinical findings: retinal dystrophy, optic nerve edema, splenomegaly, anhidrosis, and headache. Reports have documented approximately 70 cases since the first description in 2012.

Materials and Methods. We describe the case of a 22-year-old woman who presented in 2021 with bilateral progressive visual loss, dyschromatopsia, frontal headache, and severe fatigue. Ophthalmologic examination revealed bilateral papilledema, vitreous inflammation, macular edema, retinal dystrophy, retinal vascular inflammation, and neurodegeneration of outer retinal layers. Neuroimaging was unremarkable, but lumbar puncture showed elevated opening pressure (27 mmHg). Splenomegaly (13 cm) was detected on abdominal ultrasound. Laboratory tests are reported in the Table. An initial diagnosis of atypical systemic lupus erythematosus (SLE) was made, and high-dose corticosteroids were started (pulsed methylprednisolone followed by tapering oral prednisone). Additional treatments included low-dose aspirin (100 mg/day) and acetazolamide (1250 mg/day). The patient was treated subsequently with steroid-sparing drugs: azathioprine (2 mg/kg/day) and hydroxychloroquine (200 mg/day) later switched to mycophenolate mofetil (3 g/day), and then rituximab (1 g every two weeks, 2 doses). These treatments improved visual acuity and vitreous inflammation but had a limited effect on papilledema and retinal dystrophy. For these conditions, corticosteroids were the only effective treatment. In 2023, the patient was referred to our center: attempts to taper corticosteroids and acetazolamide resulted in the recurrence of headaches and ocular symptoms, along with worsening macular edema. Additionally, she exhibited hypohidrosis. Clinical reassessment revealed that her father had progressive blindness and severe papilledema secondary to hypertensive hydrocephalus.

Results. Given these findings, the patient underwent molecular genetic testing (next-generation sequencing (NGS) panel for autoinflammatory diseases). A heterozygous missense pathogenic variant in ALPK1 (c.710C>T; p.Thr237Met) was identified, confirming the diagnosis of ROSAH syndrome. In December 2024, treatment with tocilizumab (8 mg/kg every 4 weeks) was started. After 4 months, the patient showed significant improvement in papilledema and complete recovery of visual acuity along with resolution of systemic symptoms, despite continued tapering of prednisone (7.5 mg/day) and acetazolamide (750 mg/day).

Conclusions. ROSAH syndrome is an emerging autoinflammatory disorder with limited documented cases. This report highlights its diagnostic complexity and therapeutic challenges. Tocilizumab, an anti-IL-6 receptor antibody, appears to be a well-tolerated and effective treatment, especially for ocular manifestations. Further studies are needed to better understand the pathogenesis and to establish standardized treatment protocols.