Macroglossia and Periorbital Purpura as Early Red Flags of Al Amyloidosis Associated With Multiple Myeloma

Background AL amyloidosis is a rare systemic disorder related to plasma cell dyscrasias and caused by deposition of monoclonal light chains. Cardiac involvement is the main prognostic determinant. Macroglossia is an uncommon manifestation, usually described in advanced disease stages. Case Report A 61–year–old woman with obesity (BMI 39), smoking history, hypertension, dyslipidemia, and hypothyroidism presented to her general practitioner with progressive macroglossia and periorbital and labial purpura lasting two months. Screening for amyloidosis red flags was positive for macroglossia, periorbital and labial purpura, previous bilateral carpal tunnel surgery, chronic constipation, and lower–limb sensory disturbances. Laboratory tests showed hemoglobin 11.9 g/dL, creatinine 0.56 mg/dL, NT–proBNP 171 ng/L, and high–sensitivity troponin 17 ng/L. Serum and urine immunofixation revealed markedly elevated free lambda light chains (1060 mg/L), without proteinuria. Genetic testing for transthyretin mutations was negative. Electrocardiogram was unremarkable. Transthoracic echocardiography showed mild concentric left ventricular hypertrophy with preserved systolic function (LVEF 55%), LV global longitudinal strain −17.7%, left atrial enlargement (LAVi 59 mL/m²), impaired atrial function (PALS 16%, PACS −8%), grade I diastolic dysfunction, and relative apical sparing (RELAPS 0.88). Minor salivary gland biopsy demonstrated Congo red–positive amyloid deposits. Bone marrow biopsy revealed IgG/lambda multiple myeloma with monoclonal plasma cell infiltration. Cardiac magnetic resonance excluded cardiac involvement. Conclusions This case highlights the importance of early recognition of AL amyloidosis red flags, even in the primary care setting. In the literature, macroglossia and periorbital purpura are usually described as late manifestations associated with poor prognosis. However, although rare, they may represent early clinical signs, allowing prompt diagnosis and potentially improving prognosis and therapeutic options.