Case Presentation: A 24 year old Afro-Caribbean woman with no medical history presented with intermittent facial swelling of one month, several months of fatigue, anorexia and unintentional weight loss of 65 pounds. The swelling initially involved the lower face with gradual spread to bilateral peri-orbital areas. There was no urticaria, rash, dysphagia, dyspnea or visual disturbances. She denied any recent dietary changes, drug exposure, family history of autoimmune disease or angioedema. Examination revealed a lethargic woman with swelling to both lips, edema of the buccal cavity, peri-orbital region and severe conjunctival chemosis. There were no mucosal ulcers, skin rash, alopecia or synovitis. The rest of the examination was unremarkable. Laboratory tests revealed anemia, leukopenia, lymphopenia and thrombocytopenia. Serology showed antinuclear antibody titer of 1:5120, anti-double stranded DNA 16 (0-10 IU/ml), Smith antibodies 136 (0-7 EU/ml), low C3/C4, low C1 inhibitor (< 50 % normal) and low C1q levels 4.7 (11.8 - 24.4 mg/dl). 24 hour urine collection showed 640 mg of protein but no casts. Small bilateral pleural effusions were seen on chest radiograph. The diagnosis of SLE was made based on Systemic Lupus International Collaborating Clinics (SLICC) criteria and acquired C1 esterase inhibitor deficiency secondary to autoimmunity was deemed most likely based on C4, C1q and C1-INH levels. She was treated with pulse dose methylprednisolone followed by maintenance prednisone with resolution of angioedema.
Discussion: Systemic lupus erythematosus (SLE) is a chronic multi-organ autoimmune disease characterized by autoantibody production and immune complex formation. The heterogenic nature of this disease accounts for its variable manifestations. Acquired angioedema (AAE) due to C1 esterase inhibitor deficiency, also called C1INH -AAE, is a rare and possibly underdiagnosed entity. The prevalence is reported to be 1 in 500,000 in the general population. It is most commonly found in association with lymphoproliferative disorders but significantly much less with autoimmune conditions. The diagnosis of C1INH -AAE should be considered in patients presenting with episodes of recurrent angioedema without urticaria, negative family history of angioedema and age of onset after the fourth decade. The presence of low C4 and C1 inhibitor is indicative of C1 inhibitor deficiency, while a low C1q level establishes the diagnosis of C1INH – AAE, as in this patient.
The age of onset is the most significant clinical difference between hereditary and acquired angioedema; this case is unique given that the patient’s age of presentation was below the fourth decade, which is almost exclusive to hereditary angioedema. The laboratory findings however, substantiate the diagnosis of C1INH -AAE.
Conclusions: Based on this patient’s clinical presentation, there was a high suspicion of SLE with associated C1INH-AAE. Clinicians should be aware of this unusual presentation of SLE, as delay in treatment could result in adverse patient outcomes.