Diagnostic Dilemma: Systemic Lupus Erythematosus and Antiphospholipid Antibody Syndrome

Department Editor: Tania Phillips, MD, FRCPC Overall Learning Objectives: The physician or podiatrist participant will develop a rational approach to the evaluation and treatment of a variety of uncommon wounds and will have an increased awareness of the differential diagnosis of cutaneous wounds and the systemic diseases associated with these wounds. Submissions: To submit a case for consideration in Diagnostic Dilemmas, e-mail or write to: Executive Editor, WOUNDS, 83 General Warren Blvd., Suite 100, Malvern, PA 19355, eklumpp@hmpcommunications.com Completion Time: The estimated time to completion for this activity is 1 hour. Target Audience: This CME/CPME activity is intended for dermatologists, surgeons, podiatrists, internists, and other physicians who treat wounds. At the conclusion of this activity, the participant should be able to: 1. Discuss one presentation of venous leg ulcer in a patient with systemic lupus erythematosus 2. Describe the association of antiphospholipid antibodies and leg ulcers 3. Explain other cutaneous manifestations associated with antiphospholipid antibodies 4. Identify types of antiphospholipid antibodies 5. Summarize management of this patient's leg ulcer. Disclosure: All faculty participating in Continuing Medical Education programs sponsored by HMP Communications, LLC, are expected to disclose to the program audience any real or apparent conflict(s) of interest related to the content of their presentation. Drs. Lin and Phillips disclose no financial conflicts. Accreditation: HMP Communications, LLC, is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. HMP Communications, LLC, is approved by the Council on Podiatric Medical Education as a sponsor of continuing education in podiatric medicine. Designation: HMP Communications, LLC, designates this continuing medical education activity for 1 credit hour in Category 1 of the Physician's Recognition Award of the American Medical Association. Each physician should claim only those hours he/she spent in the educational activity. HMP Communications designates this continuing medical activity for .1 CEUs available to participating podiatrists. Method of Participation: Read the article, take, submit, and pass post-test by August 15, 2003. This activity has been planned and produced in accordance with the ACCME Essential Areas and Policies. Release date: August 15, 2002 Expiration date: August 15, 2003 Presentation A 40-year-old Caucasian woman with systemic lupus erythematosus presented with a 10-day history of blisters on her right shin. The blisters were filled with a clear fluid and were painful. She noted surrounding erythema and warmth around the blisters but denied fevers or chills. She did not have any blisters in her mouth or on her genitalia. She treated the area with hydrocortisone valerate cream and had been started on minocycline by her primary care physician. Her other medications included methotrexate, chloroquine, warfarin, celecoxib, folic acid, and acetaminophen. She was adopted and unaware of any family history of blistering disease. Her main manifestations of systemic lupus erythematosus were fatigue and mouth sores, as well as joint pains in her knees and hands. She has had a history of renal disease, alopecia, and butterfly rash. She has also had two prior episodes of deep venous thromboses and a history of a leg ulcer, which healed but was complicated by cellulitis. Physical Examination Physical examination revealed a normal-appearing Caucasian female. Her head, neck, oral mucosa, chest, abdomen, back, upper extremities, and genitalia were within normal limits. Her legs showed a marked livedo reticularis pattern bilaterally. On the right shin, there were two superficial erosions measuring 9cm x 12cm and 5cm x 2cm with surrounding erythema and warmth. Hemosiderin pigmentation was present on her shin. The rest of her lower extremities were cool with palpable pulses. Initial diagnostic considerations included cellulitis, bullous lupus erythematosus, and antiphospholipid antibody syndrome (Figure 1). Investigations Her double stranded DNA was 8.6 IU/mL (normal is Physical examination. Skin manifestations may occur early in the course of APA syndrome. Recurrent thromboses are a major clinical manifestation of the APA syndrome.6 APA-TS should be thought of as part of the differential diagnosis of livedo reticularis, acrocyanosis, ulceration, Raynaud's phenomenon, and purpuric macular lesions.7 Livedo reticularis, a violaceous discoloration of the skin in a network or lace-like pattern, is probably the most recognized common manifestation of APA7,8 and occurs in 20 to 50 percent of patients with APA-TS.7 Although it may be recognized in other diseases, such as cryoglobulinemia, polyarteritis nodosa, cholesterol embolization, and infections, such as tuberculosis and syphilis, livedo reticularis has been correlated with increased levels of ACLA.9 Leg ulcers have been described as the presenting feature of APS with the description as having the appearance of pyoderma gangrenosum5,10-12 or superficial ulcerations with a surrounding purple halo.5,10,11 Leg ulcers associated with APA tend to occur in young patients and occur on the lower extremities.5 They tend to be sharply demarcated and located on the pretibial area or ankle.8 Ulcers are frequently multiple and bilateral.6 Cutaneous necrosis may occur on the legs, face, and ears or may be generalized.7,13,14 Digital ischemia and digital gangrene have been reported secondary to arterial occlusion of the hands and feet.11 Edema and erythema of the lower extremities from thrombophlebitis has also been observed.7,8,12 Other manifestations associated with APA include porcelain-white scars,15 subungal splinter hemorrhages,8 painful nodules resembling vasculitis, purpuric or cyanotic macules, blue toes syndrome, and purpura fulminans.7 Some patients do not develop thrombosis.6 It is not well understood why some patients with APA develop clinical manifestations and others do not.6 Risk factors for thrombosis include a history of thrombosis (which is the greatest risk factor for future thrombotic events), smoking, hypertension, and oral contraceptives.6 Pathogenesis. The mechanism of the prothrombotic state has not been definitively elucidated but very likely is immune mediated and involves b2-gylcoprotein-I, platelet aggregation, endothelial cell function, or the protein C pathway. It is postulated that ACLA plays a role in the leukocyte trapping pathogenesis theory of venous ulceration in which proteolytic enzymes are released and damage endothelial cells. Endothelial cell damage would lead to immune responses involving phospholipids.1,10 Another theory is that ACLA triggers platelet activation and aggregation leading to microthrombi formation and the development of venous ulceration.10 Livedo reticularis most likely is secondary to stasis of blood caused by occlusion in the superficial drainage systems in the skin.5,7 Thrombosis may occur in the peripheral deep veins and arteries, cerebrovascular arteries, and less frequently, retinal veins and arteries. Histopathology. Noninflammatory vascular thrombosis (arterial and venous) with endothelial damage, early edema and hemorrhage, and diffuse coarse deposits of iron are present.8 Treatment. There is currently a lack of consensus for specific anticoagulant and antiplatelet prophylaxis for patients with APA-associated thrombosis.8 High-dose warfarin has been the recommended treatment of choice for venous or arterial thrombosis in these patients.16 Patient Management Antibiotics were changed to dicloxacillin. Topical steroids were discontinued in favor of a topical antibiotic. The rest of the patient's medications were unchanged. Light compression (20-30mmHg) was recommended for the legs. The patient healed well with no recurrence of blisters or ulcers (Figure 2) but had hyperpigmented patches on the areas of skin previously involved by the blistering lesions on her lower extremities. How to obtain educational credits by reading this article: Successful completion entails scoring at least 70 percent on the questions, completing the entire evaluation form, and submitting it online (or printing if off and faxing it or mailing it to the correct address listed below). Certificates will be mailed to those who successfully complete the learning assessment by August 15, 2003. Fax the completed form to (610) 560-0501 or mail the completed form to: Trish Levy, CME Director HMP Communications, LLC 83 General Warren Blvd. Suite 100 Malvern, PA 19355 Questions 1. What percentage of patients with systemic lupus erythematosus and secondary antiphospholipid antibody syndrome experience leg ulcers? A) 3 B) 25 C) 45 D) 50 E) 60 2. Antiphospholipid antibody syndrome is associated with all of the following except: A) Livedo reticularis B) Venous ulcers C) Atherosclerosis D) Recurrent spontaneous abortion E) Premature cataract formation 3. Livedo reticularis has been observed in approximately what percentage of patients with APA? A) 2 B) 10 C) 15 D) 50 E) 80 4. Cutaneous necrosis in patients with APA-TS develops in what distribution? A) Face B) Ears C) Legs D) Generalized E) All of the above 5. Antiphospholipid antibodies represent different entities. These include which of the following? A) Lupus anticoagulant B) Anticardiolipin antibody C) Other subgroups of antiphospholipids, including b2-glycoprotein-I, phosphatidylserine, phosphatidylethanolamine, phosphatidylglycerol, phosphatidylinositol, and phosphatidylcholine D) A and B E) A, B, and C Systemic Lupus Erythematosus and Antiphospholipid Antibody Syndrome Answer Form and Evaluation Please print clearly: Name, Degree, Position/Title Organization/Institute, Department Mailing Address for Certificate (H or W): City, State, Zip Code, Email Address Social Security Number, Phone (with area code), Fax (with area code) Answers (Refer to questions above) Click on or circle one letter for each answer: 1. A B C D E 2. A B C D E 3. A B C D E 4. A B C D E 5. A B C D E Evaluation--Excellent (4) Good (3) Satisfactory (2) Poor (1) Accuracy and timeliness of content: 4 3 2 1 Relevance to your daily practice: 4 3 2 1 Impact on your professional effectiveness: 4 3 2 1 Relevance of the content to the learning objectives: 4 3 2 1 Effectiveness of the teaching/learning methods: 4 3 2 1 This activity avoided commercial bias or influence YES NO Now that you have read this article, can you: 1. Discuss one presentation of venous leg ulcer in a patient with systemic lupus erythematosus? YES NO 2. Describe the association of antiphospholipid antibodies and leg ulcers? YES NO 3. Explain other cutaneous manifestations associated with antiphospholipid antibodies? YES NO 4. Identify types of antiphospholipid antibodies? YES NO 5. Summarize management of this patient's leg ulcer? YES NO What questions do you still have?_______________________________________________________________________________ How will you use what you have learned from this activity?___________________________________________________ All tests must be received by 8/15/03.