Trường hợp U lympho vùng rìa lách biểu hiện là Phù mạch mắc phải

Abstract

Acquired angioedema (AAE-C1INH) is a rare, potentially life-threatening disorder resulting from acquired C1 esterase inhibitor deficiency, often secondary to lymphoproliferative diseases such as splenic marginal zone lymphoma (SMZL). We report on a 68-year-old woman presenting with facial and tongue swelling, gastrointestinal symptoms, and splenomegaly. Laboratory work-up revealed low C1 esterase inhibitor and C1q complement levels, consistent with AAE-C1INH. Imaging showed marked splenomegaly with increased fluorodeoxyglucose uptake; bone marrow biopsy confirmed SMZL. Treatment with rituximab and bendamustine chemotherapy led to clinical improvement, normalization of complement levels, and cessation of angioedema episodes.

Background

Acquired angioedema (AAE-C1INH) is a rare disorder caused by acquired deficiency or dysfunction of C1 esterase inhibitor (C1-INH), leading to recurrent, nonpitting, nonpruritic swelling of the skin and mucosal tissues 1–3. Unlike hereditary angioedema, which results from genetic mutations, AAE-C1INH commonly develops secondary to autoimmune diseases, lymphoproliferative disorders, or malignancies 1–3. Among lymphoid neoplasms, splenic marginal zone lymphoma (SMZL), a rare indolent B-cell non-Hodgkin lymphoma involving the spleen and bone marrow, has been increasingly recognized as an important cause of AAE-C1INH 2–4. Diagnosing SMZL can be difficult owing to its subtle and often indolent clinical course, yet early recognition is important because appropriate lymphoma-directed therapy can improve or resolve angioedema 1, 2, 5. We describe a case highlighting this association and discuss the underlying pathophysiology, differential diagnosis, and therapeutic considerations.

Case Report

A 68-year-old woman presented to the emergency department with acute onset of facial and tongue swelling. She also reported 2 episodes of severe abdominal cramping followed by explosive diarrhea. These gastrointestinal symptoms were accompanied by persistent left upper quadrant abdominal pain, intermittent fever, night sweats, and an unintentional weight loss of approximately 4.5 kg over the preceding weeks.

Physical examination revealed conspicuous splenomegaly, with the spleen palpable 5 cm below the left costal margin. No peripheral lymphadenopathy was noted. Laboratory investigations showed anemia, with a reduction in hemoglobin from her baseline of 13.6 g/dL to 10 g/dL and mild leukopenia, whereas platelet counts remained within normal limits. There was no history or clinical evidence of bleeding. Further evaluation for angioedema revealed significantly reduced levels of C1-INH and C1q complement, consistent with acquired angioedema (Table 1). Contrast-enhanced computed tomography of the abdomen and pelvis confirmed marked splenomegaly measuring approximately 18 cm in greatest dimension, correlating with the site of left upper quadrant discomfort. A positron emission tomography scan demonstrated fluorodeoxyglucose-avid splenomegaly without evidence of fluorodeoxyglucose-avid lymphadenopathy, raising suspicion for lymphoma.

A subsequent bone marrow biopsy was performed to evaluate for lymphoproliferative disorder. Histopathology identified a low-level infiltrate of abnormal small mature CD20-positive B cells (CD5 negative, CD10 negative) comprising 1.26% of the nucleated cells on flow cytometry and 1% to 15% CD20-positive B cells on immunohistochemistry (Figure 1, A and B). The marrow was mildly hypercellular (40%–50%), with preserved trilineage hematopoiesis and multiple small lymphoid aggregates. There was no increase in blasts. Molecular testing for MYD88 and CXCR4 mutations was negative. These findings supported the diagnosis of a low-grade B-cell lymphoma consistent with SMZL. The final clinical diagnosis was SMZL-associated acquired angioedema.

Given her symptomatic lymphoma and angioedema, treatment was initiated with the combination of rituximab and bendamustine chemotherapy. Given the risk for recurrent angioedema, icatibant acetate was prescribed for on-demand treatment of acute attacks; however, the patient never required its use. Following initiation of therapy, the patient exhibited marked clinical improvement with resolution of night sweats, reduction in splenomegaly on physical examination, and complete cessation of angioedema episodes. Laboratory reassessment showed normalization of C1-INH and C1q complement levels (Table 1). Repeat imaging after treatment showed complete resolution of splenomegaly.

Discussion

AAE-C1INH results from acquired C1-INH deficiency, most often secondary to consumption or inactivation by autoantibodies or abnormal B-cell clones in lymphoproliferative disorders 1–3. C1-INH normally regulates activation of the classical complement pathway and the kallikrein–kinin system; its deficiency leads to uncontrolled bradykinin generation, increased vascular permeability, and subsequent tissue edema 2, 3. In B-cell neoplasms such as SMZL, clonal B cells may produce anti-C1-INH antibodies or otherwise consume the inhibitor, thereby precipitating angioedema 2, 6–8.

Clinically, AAE-C1INH presents with recurrent, nonpruritic angioedema without urticaria, involving the skin, airway, or gastrointestinal tract 1–3, 9–11. Laboratory distinction from hereditary angioedema (HAE) is crucial: both entities show low C1-INH levels and low C4, but C1q is typically decreased in AAE-C1INH and normal in hereditary angioedema 1–3.

Management of AAE-C1INH involves both short-term control of angioedema and long-term treatment of the underlying disorder 1–3. Acute episodes are best managed with C1-INH concentrate, bradykinin B2 receptor antagonists, or kallikrein inhibitors. Definitive therapy focuses on the associated lymphoproliferative disease; in SMZL, options include rituximab monotherapy, rituximab-based chemoimmunotherapy, or splenectomy, with treatment generally indicated for symptomatic splenomegaly or cytopenias 3, 5. In our patient, lymphoma-directed therapy led to cessation of angioedema episodes and normalization of complement variables, reinforcing the importance of evaluating for an underlying lymphoproliferative disorder such as SMZL in patients presenting with acquired C1-INH deficiency and angioedema 2, 5, 8.