Abstract

This case illustrates a rare and unique case of a 46-year-old man who presents with acute rapidly decreasing oxygen saturation, oliguria, acute renal failure, syncope, ventricular fibrillation after cardiopulmonary resuscitation. He then developed superficial gangrene of the hands and feet in a bilaterally symmetrical fashion with positive anticardiolipin antibodies. We further discuss the process of diagnosis and current understanding of the treatment of catastrophic antiphospholipid syndrome. A high index of suspicion for early detection and prompt treatment can prevent the life-threatening consequences of this disease and reduce mortality rates.

Antiphospholipid syndrome (APS) is an autoimmune disorder defined by the presence of a hypercoagulable clinical state due to antiphospholipid antibodies [1]. Catastrophic antiphospholipid syn- drome (CAPS), a fulminant, often life-threatening manifestation of APS, was first described in 1992 [2]. CAPS is characterized by multiple vascular occlusive events, usually affecting small vessels and involving multiple organs simultaneously that develops over a Short period of time. With a mortality rate of approximately 50%, early diagnosis and aggressive therapy are essential to the management of CAPS. Current guidelines support anticoagulants and systemic glucocorticoids as the foundation of therapy for all patients, and plasma exchange and intrave- nous immunoglobulin (IVIG) may be options according to the patient’s Clinical context [3]. Here, we will describe a rare case of CAPS treated at our institution with good results.

A 46-year-old man without a history of diabetes or other co- morbidities presented to the emergency department of his local hospi- tal due to pain in his back and abdomen for 1 day and a syncopal episode for 3 minutes. The patient was married and did not take any medica- tions. He had a history of smoking and drinking for 30 years. After arrival at the hospital, his blood pressure and oxygen saturation rapidly declined. He urgently intubated, and mechanical ventilation was begun. He was given a small dose of dopamine to maintain his blood pressure. He was admitted to the intensive care ward of the local hospital for management and further work up. At 5 hours after admission, the patient went into ventricular fibrillation, but spontane- ous cardiac rhythm was restored after cardiopulmonary resuscitation

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for 20 minutes. The second day after admission, the patient was noted to have swelling and discoloration of the toes and the tops of fingers, and he also developed a fever, oliguria and acute renal failure. He was treated with hydrocortisone 50 mg/d for 5 days and Continuous renal replacement therapy every other day. He also received antibiotics for 14 days. His mental status and breathing recovered, and he was extubated. The black discoloration of his legs and arms rapidly spread, and cutaneous gangrene was diagnosed. Sensation in the gangrenous area was lost. To further clarify the diagnosis, he was transferred to our department for additional treatment.

On examination, his vital signs and the examination of the chest and abdomen was normal (blood pressure 132/86 mmHg, pulse rate 73 bpm, normal respiratory rate and body temperature). Physical examination revealed a bilaterally palpable synchronous Radial artery pulse, but there was no pulse in the dorsalis pedis artery. He had superficial gangrene of the 2nd, 3rd, 4th and 5th fingers of the right hand (Fig. 1) and both legs (Fig. 2). The skin temperature was low, and no ulcerations were observed in the necrotic area. He could move his hands and feet, but there was complete loss of sensation in the area of the necrotic lesions.

A detailed assessment of the cardiovascular system was unremark- able. Doppler studies showed sclerotic occlusion of the lower extremity arteries under the ankle with no significant deep venous thrombosis. Foot and hand radiographs were normal. Lung computed tomography angiography was normal, but there was a small amount of inflammation in both lungs.

Laboratory results showed elevated serum anticardiolipin antibod- ies levels (IgG N120 RU/mL, normal b12 RU/mL). The anti-nuclear anti- gen test was positive (1:100 speckled pattern), but other markers of autoimmune disease such as ENA, dsDNA, c-ANCA, p-ANCA, SS-A, SS- B, ESR, and Rheumatoid factor were negative. His CRP was 67.5 mg/L. He was anemic and thrombocytopenic (hemoglobin: 66 g/L, blood platelets: 88 x 10⁹/L). Other lab tests showed hyperkalemia (potassi- um: 5.6 nmol/L), Renal impairment (serum urea nitrogen N40 mmol/L, creatinine 649 umol/L, estimated GFR 25.9 mL/min per 1.73 m²), proteinuria (2+), elevated Liver enzymes (alanine transaminase 60 units/ml, aspartate transaminase 52 U/mL), an elevated NT-pro BNP level (29 867 pg/mL), and an elevated D-dimer level (22.76). His HIV antibody screening test, lipid profile, Blood sugar level, HbA_1c, tumor markers, blood gas analysis, protein C and Protein S level, and fac- tor V and antithrombin III levels were normal.

Based on these results, a definitive diagnosis of CAPS with gangrene was made, and the patient’s further management focused on treating this condition.

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Such cases may present a Diagnostic dilemma due to the various clinical presentations of APS. There are other forms of APS including livedo reticularis, cardiac valve vegetations, valvular insufficiency, transverse myelitis, Skin necrosis and chorea [4]. CAPS is associated with a high mortality rate. Hence, all clinicians need to be vigilant for this potentially life-threatening condition. The diagnosis of APS is based on the International Consensus statement, and the diagnostic criteria for CAPS are (1) involvement of 3 or more organs/tissues;

(2) the development of manifestations in less than a week; (3) histological evidence of intravascular thrombosis; and (4) the presence of antiphospholipid antibodies on two occasions six weeks apart [5,6].A definite diagnosis of CAPS is made when all four diagnostic criteria are present, and a diagnosis of CAPS is probable when certain combinations of these criteria are present: (1) all 4 criteria, except for only two organs, systems and/or tissues involved; (2) all four criteria, except for the absence of laboratory confirma- tion at least 6 weeks apart due to the early death of a patient never tested for antiphospholipid antibodies before CAPS;(3) criteria 1, 2 and 4 and

Fig. 1. Superficial gangrenous of 2nd,3rd, 4th and 5th fingers of the right hand.

He was treated with Intravenous heparin with daily monitoring of his APTT a target INR of 2 to 3. He was also treated with prednisolone (500 mg/d x 3 days) and IVIG (0.4 g/kg/d x 5 days) were started. The prednisolone dosage was slowly reduced (240 mg/d x 3 days, 160 mg/d x 5 days, 80 mg/d x 7 days, 40 mg/d maintenance). He was trans- fused two units of blood due to his anemia and was continued on con- tinuous renal replacement therapy, antibiotics and supportive care. A few days later, his blood platelet count decreased rapidly to 43 x 10⁹/L without evidence of hemorrhage. His IV heparin had to be discontinued, and his anticoagulation was changed to apixaban. With therapeutic anticoagulation, IVIG, prednisolone and continuous renal replacement therapy, his renal impairment and blood counts improved, and the gan- grenous spread was controlled. The infection regressed slowly, and he regained partial touch sensation. His serum IgG anticardiolipin antibod- ies decreased to 34.7 RU/mL. Ultimately, he was transferred to his local hospital where he was evaluated by Orthopedic surgeons who decided that amputation of the 4 affected fingers of the right hand and a 30 cm under-the-knee amputation were needed. His disease was stable after amputation.

After 3-month follow-up, he was discharged from the hospital in good health having recovered from this potentially fatal episode of CAPS.

This case report describes a rare and a unique presentation of CAPS. The combination of acute rapidly decreasing oxygen saturation, oliguria, acute renal failure, syncope, ventricular fibrillation and superfi- cial gangrene of the hands and feet in a bilaterally symmetrical fashion as presenting features of CAPS to our knowledge has not been described before.

Fig. 2. Superficial gangrenous of both legs.

(4) criteria 1, 3 and 4 and the development of a third event after more than a week but less than a month despite anticoagulation [7]. The CAPS Registry, which contains clinical, laboratory, and therapeutic data on all reported cases of CAPS, with approximately 300 patients as of November 2008 [8], shows that approximately 72% of patients with CAPS were women. The kidneys are the most commonly affected organ, with a proportion of 71%, and cutane- ous manifestations are observed in nearly half of the patients. The rapid onset and progression of symptoms, combined with widespread microvascular thrombosis and positive anticardiolipin Antibody testing in the current case, support the diagnosis of CAPS.

It is essential to start treatment as soon as the syndrome is suspected. According to the recent literature [3,9], a treatment that sig- nificantly reduces mortality in patients with CAPS is combination ther- apy including anticoagulation (AC), glucocorticoids (CS), and therapeutic plasma exchange (PE) with or without IVIG. AC + CS is the most commonly used regimen (19.8%), followed by AC + CS + PE and/or IVIG (17.4%). The highest recovery rate is achieved by the combina- tion of AC + CS + PE (77.8%), followed by AC + CS + PE and/or IVIG (69%) [10]. Anticoagulant therapy including heparin and/or warfarin can reduce the mortality rate [11]. Corticosteroids have been proposed as a means to blunt the inflammatory aspects of CAPS and are recommended by most ex- perts [8]. Although no dosing regimen is evidence based in CAPS, expert consensus favors the use of high doses (eg, methylprednisolone 500 mg daily x 3 days), and then the dose of glucocorticoids is reduced to 1 mg/kg and tapered off depending on the clinical condition. IVIG has multi- ple therapeutic activities and improves outcomes based on the data in the CAPS Registry [12]. In the current case, recovery was achieved with heparin followed by apixaban therapy, methylprednisolone and IVIG.

In conclusion, antiphospholipid antibody syndrome is a potentially dev- astating disease process. Therefore, we should pay close attention to those patients with an acute episode of CAPS. Otherwise, it is very difficult to save the patients without early diagnosis and subsequent treatment.

Shuixiang Deng, MD

Jun Shen, AD Jie Ni, MD Ye Gong, AD

Hechen Zhu, MD?

Department of Intensive Care Unit, HuaShan Hospital, Fudan University

Shanghai, China

?Corresponding author. Department of Intensive Care Unit HuaShan Hospital, Fudan University, 12 of wu lu mu qi Middle Road, Shanghai, China, 200040. Tel.: +86 21 5288 7353

E-mail address: [email protected]

http://dx.doi.org/10.1016/j.ajem.2016.06.086

S. Deng et al. / American Journal of Emergency Medicine 35 (2017) 191.e3–191.e5 191.e5

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