Clin Rheumatol (2014) 33:429–433 DOI 10.1007/s10067-013-2454-5
CASE BASED REVIEW
Recurrent episodes of hemorrhagic alveolitis in relapsing catastrophic antiphospholipid syndrome: the same side of the dark moon Filippo Pieralli & Maddalena Grazzini & Vieri Vannucchi & Antonio Mancini & Daniele Cammelli & Carlo Nozzoli
Received: 28 August 2013 / Revised: 28 October 2013 / Accepted: 27 November 2013 / Published online: 21 December 2013 # Clinical Rheumatology 2013
Abstract Catastrophic antiphospholipid syndrome (CAPS) is a rare variant of antiphospholipid syndrome characterized by widespread thrombotic microangiopathy and multiorgan failure. Clinically, CAPS signs and symptoms can mimic vasculitis of systemic lupus erythematosus, disseminated intravascular coagulation, and thrombotic thrombocytopenic purpura. CAPS is burdened by high mortality, nearly 50 % in most series. However, patients surviving the acute phase rarely suffer of CAPS relapses. Moreover, concomitant pulmonary hemorrhagic alveolitis is a very rare complication warranting an ominous prognosis. Only few reports of relapsing CAPS are described in literature, and pathogenetic mechanisms are poorly understood and the optimal treatment is yet unknown. We report a case of a young man suffering from multiple relapses of CAPS and recurrent hemorrhagic pulmonary alveolitis refractory to aggressive combination treatment.
syndrome (APS) characterized by diffuse thrombotic microangiopathy, high levels of antiphospholipid (aPL) antibodies, rapid clinical progression, and high mortality [2]. Classical APS is characterized by relapsing thrombosis affecting medium and large size venous and/or arterial vessels, while small vessels thrombosis occur in CAPS, relapses are very rare and only few cases of relapsing CAPS have been reported [3–5]. Mortality rate is nearly 50 % despite early and aggressive treatment with anticoagulants, steroids, immunosuppressive drugs, intravenous immunoglobulin (IVIG), and plasma exchange [6, 7]. Herein, we report a case of a patient who suffered from ultimately fatal relapses of catastrophic APS with hemorrhagic pulmonary alveolitis.
Keywords Antiphospholipid syndrome . Asherson's syndrome . Pulmonary hemorrhage
A 29-year-old man was admitted to our medical unit on March 13, 2011 for progressive dyspnea and hemoptysis. He reported three episodes of self-limiting hemoptysis in the past 2 months, but he did not seek medical attention. His medical history was remarkable for APS diagnosed 10 years earlier when he was admitted to this hospital for an episode of transient ischemic attack. Since that time, he was on anticoagulant treatment with warfarin maintaining satisfactory anticoagulation over the time. In the following years, he developed obesity, hypertension treated with losartan, carvedilol, and amlodipine, chronic renal failure (serum creatinine levels of 1.7 mg/dl, creatinine clearance of 60 ml/min), and recurrent bilateral ankle ulcers due to chronic venous stasis. He had a six pack-year smoking history and in the past indulged in recreational cocaine and alcohol use. He reported cocaine use cessation some years earlier, soon after the diagnosis of APS. He worked as a clerk in a general store. Physical examination at hospital admission showed obesity (BMI, 38.5), bilateral ankle pitting edema, and sparse bilateral
Introduction Catastrophic antiphospholipid antibodies syndrome (CAPS) was firstly described by Asherson in 1992 [1], and for that reason, it is also known with the eponym of Asherson's syndrome. CAPS is a rare variant of antiphospholipid F. Pieralli : M. Grazzini (*) : V. Vannucchi : A. Mancini : C. Nozzoli Internal and Emergency Medicine Unit, Careggi University Hospital, Largo Brambilla 3, 50134 Florence, Italy e-mail: [email protected] D. Cammelli Clinical Rheumatology Unit, Careggi University Hospital, Florence, Italy
Case report
430
Clin Rheumatol (2014) 33:429–433
crackles on both lung bases. Cardiac, abdominal, and neurological examination was normal. Blood gas analysis on room air showed hypoxic respiratory failure (pH 7.52, pO2 of 44 mmHg, pCO2 of 23 mmHg, SatO2 of 81 %, HCO3 of 24 mmol/L), and blood tests revealed hemolytic anemia with three schistocytes per field in the blood smear, thrombocytopenia, and worsening renal failure; a toxicological screening test was negative for the presence of cocaine (Table 1). A contrast-enhanced thoracic–abdominal CT scan showed bilateral diffuse ground-glass lesions suggestive of alveolar hemorrhages (Fig. 1, panel a), multiple thoracic and abdominal lymphadenopathies (maximal diameter, 3.5 cm), and splenomegaly (18 cm). There were neither signs of pulmonary embolism nor signs of active bronchial artery bleeding on the chest imaging. An echocardiogram showed diffuse hypokinesia and ventricular dilatation with moderate systolic dysfunction (ejection fraction, 45 %) and moderate mitral regurgitation. The history of APS along with recurrent episodes of hemorrhagic alveolitis and worsening renal failure suggested a diagnosis of associated systemic vasculitis or CAPS; therefore, IVIG (0.4 g−1kg−1day−1 for 5 days) and pulsed high-dose
methylprednisolone boluses (1 g/day for 3 days) were started. He was transfused with four units of packed red blood cells. During inhospital course, clinical condition improved as well as radiologic findings on the chest CT scan. On the 15th day, after resolution of respiratory failure and restoring of preadmission renal function, the patient was discharged on warfarin and prednisone therapy (50 mg/day) along with antihypertensive medications. Six weeks after discharge, the patient had a recurrence of hemoptysis with respiratory failure needing urgent hospital admission. Blood tests revealed worsening anemia and renal failure (Table 1). A thoracic CT scan showed significant increase of diffuse alveolar hemorrhage and diffuse lymphadenopathy (Fig. 1, panel b). High-dose pulsed methylprednisolone boluses and IVIG were then repeated. A bronchoscopy confirmed the presence of blood within both lungs. Microbiologic tests and cultures for bacteria, fungi, pneumocystis, herpes virus, and mycobacteria and search for neoplastic cells from bronchoalveolar lavage were negative. Due to the presence of widespread large lymphadenopathy and splenomegaly, differential diagnostic procedures were performed. Bone marrow biopsy and
Table 1 Relevant laboratory findings and their time course Variables
Blood and urine chemistry Hemoglobin (g/dL) Reticulocytes (%) Platelets (109/L) Haptoglobin (g/L) LDH (UI/L) Direct and indirect Coombs' test Schistocytes (per field) INR PT (%) aPTT (s) Serum Creatinine (mg/dL) Urea (g/L) Urinary RBC (n/microL) Proteinuria (mg/dL) Toxicological cocaine urine test Immunological profile ANA, anti-ENA antibodies, ANCA, anti-GBM antibodies, crioglubuline, ACCP antibodies, rheumatoid factor Anticardiolipin antibodies IgG (GPLU/mL) Anti-beta 2 GP1 antibodies IgG (GPLU/mL) Lupus anticoagulant
First hospital After 15 days After 8 weeks After 11 weeks Reference admission (hospital discharge) (first recurrence) (hospital discharge) values
5 3 50.000
CASE BASED REVIEW
Recurrent episodes of hemorrhagic alveolitis in relapsing catastrophic antiphospholipid syndrome: the same side of the dark moon Filippo Pieralli & Maddalena Grazzini & Vieri Vannucchi & Antonio Mancini & Daniele Cammelli & Carlo Nozzoli
Received: 28 August 2013 / Revised: 28 October 2013 / Accepted: 27 November 2013 / Published online: 21 December 2013 # Clinical Rheumatology 2013
Abstract Catastrophic antiphospholipid syndrome (CAPS) is a rare variant of antiphospholipid syndrome characterized by widespread thrombotic microangiopathy and multiorgan failure. Clinically, CAPS signs and symptoms can mimic vasculitis of systemic lupus erythematosus, disseminated intravascular coagulation, and thrombotic thrombocytopenic purpura. CAPS is burdened by high mortality, nearly 50 % in most series. However, patients surviving the acute phase rarely suffer of CAPS relapses. Moreover, concomitant pulmonary hemorrhagic alveolitis is a very rare complication warranting an ominous prognosis. Only few reports of relapsing CAPS are described in literature, and pathogenetic mechanisms are poorly understood and the optimal treatment is yet unknown. We report a case of a young man suffering from multiple relapses of CAPS and recurrent hemorrhagic pulmonary alveolitis refractory to aggressive combination treatment.
syndrome (APS) characterized by diffuse thrombotic microangiopathy, high levels of antiphospholipid (aPL) antibodies, rapid clinical progression, and high mortality [2]. Classical APS is characterized by relapsing thrombosis affecting medium and large size venous and/or arterial vessels, while small vessels thrombosis occur in CAPS, relapses are very rare and only few cases of relapsing CAPS have been reported [3–5]. Mortality rate is nearly 50 % despite early and aggressive treatment with anticoagulants, steroids, immunosuppressive drugs, intravenous immunoglobulin (IVIG), and plasma exchange [6, 7]. Herein, we report a case of a patient who suffered from ultimately fatal relapses of catastrophic APS with hemorrhagic pulmonary alveolitis.
Keywords Antiphospholipid syndrome . Asherson's syndrome . Pulmonary hemorrhage
A 29-year-old man was admitted to our medical unit on March 13, 2011 for progressive dyspnea and hemoptysis. He reported three episodes of self-limiting hemoptysis in the past 2 months, but he did not seek medical attention. His medical history was remarkable for APS diagnosed 10 years earlier when he was admitted to this hospital for an episode of transient ischemic attack. Since that time, he was on anticoagulant treatment with warfarin maintaining satisfactory anticoagulation over the time. In the following years, he developed obesity, hypertension treated with losartan, carvedilol, and amlodipine, chronic renal failure (serum creatinine levels of 1.7 mg/dl, creatinine clearance of 60 ml/min), and recurrent bilateral ankle ulcers due to chronic venous stasis. He had a six pack-year smoking history and in the past indulged in recreational cocaine and alcohol use. He reported cocaine use cessation some years earlier, soon after the diagnosis of APS. He worked as a clerk in a general store. Physical examination at hospital admission showed obesity (BMI, 38.5), bilateral ankle pitting edema, and sparse bilateral
Introduction Catastrophic antiphospholipid antibodies syndrome (CAPS) was firstly described by Asherson in 1992 [1], and for that reason, it is also known with the eponym of Asherson's syndrome. CAPS is a rare variant of antiphospholipid F. Pieralli : M. Grazzini (*) : V. Vannucchi : A. Mancini : C. Nozzoli Internal and Emergency Medicine Unit, Careggi University Hospital, Largo Brambilla 3, 50134 Florence, Italy e-mail: [email protected] D. Cammelli Clinical Rheumatology Unit, Careggi University Hospital, Florence, Italy
Case report
430
Clin Rheumatol (2014) 33:429–433
crackles on both lung bases. Cardiac, abdominal, and neurological examination was normal. Blood gas analysis on room air showed hypoxic respiratory failure (pH 7.52, pO2 of 44 mmHg, pCO2 of 23 mmHg, SatO2 of 81 %, HCO3 of 24 mmol/L), and blood tests revealed hemolytic anemia with three schistocytes per field in the blood smear, thrombocytopenia, and worsening renal failure; a toxicological screening test was negative for the presence of cocaine (Table 1). A contrast-enhanced thoracic–abdominal CT scan showed bilateral diffuse ground-glass lesions suggestive of alveolar hemorrhages (Fig. 1, panel a), multiple thoracic and abdominal lymphadenopathies (maximal diameter, 3.5 cm), and splenomegaly (18 cm). There were neither signs of pulmonary embolism nor signs of active bronchial artery bleeding on the chest imaging. An echocardiogram showed diffuse hypokinesia and ventricular dilatation with moderate systolic dysfunction (ejection fraction, 45 %) and moderate mitral regurgitation. The history of APS along with recurrent episodes of hemorrhagic alveolitis and worsening renal failure suggested a diagnosis of associated systemic vasculitis or CAPS; therefore, IVIG (0.4 g−1kg−1day−1 for 5 days) and pulsed high-dose
methylprednisolone boluses (1 g/day for 3 days) were started. He was transfused with four units of packed red blood cells. During inhospital course, clinical condition improved as well as radiologic findings on the chest CT scan. On the 15th day, after resolution of respiratory failure and restoring of preadmission renal function, the patient was discharged on warfarin and prednisone therapy (50 mg/day) along with antihypertensive medications. Six weeks after discharge, the patient had a recurrence of hemoptysis with respiratory failure needing urgent hospital admission. Blood tests revealed worsening anemia and renal failure (Table 1). A thoracic CT scan showed significant increase of diffuse alveolar hemorrhage and diffuse lymphadenopathy (Fig. 1, panel b). High-dose pulsed methylprednisolone boluses and IVIG were then repeated. A bronchoscopy confirmed the presence of blood within both lungs. Microbiologic tests and cultures for bacteria, fungi, pneumocystis, herpes virus, and mycobacteria and search for neoplastic cells from bronchoalveolar lavage were negative. Due to the presence of widespread large lymphadenopathy and splenomegaly, differential diagnostic procedures were performed. Bone marrow biopsy and
Table 1 Relevant laboratory findings and their time course Variables
Blood and urine chemistry Hemoglobin (g/dL) Reticulocytes (%) Platelets (109/L) Haptoglobin (g/L) LDH (UI/L) Direct and indirect Coombs' test Schistocytes (per field) INR PT (%) aPTT (s) Serum Creatinine (mg/dL) Urea (g/L) Urinary RBC (n/microL) Proteinuria (mg/dL) Toxicological cocaine urine test Immunological profile ANA, anti-ENA antibodies, ANCA, anti-GBM antibodies, crioglubuline, ACCP antibodies, rheumatoid factor Anticardiolipin antibodies IgG (GPLU/mL) Anti-beta 2 GP1 antibodies IgG (GPLU/mL) Lupus anticoagulant
First hospital After 15 days After 8 weeks After 11 weeks Reference admission (hospital discharge) (first recurrence) (hospital discharge) values
5 3 50.000
