Hindawi

Case Reports in Medicine

Volume 2018, Article ID 5979386, 5 pages
https://doi.org/10.1155/2018/5979386

Case Report
Macrophage Activation Syndrome, Glomerulonephritis,
Pericarditis, and Retinal Vasculitis as Initial Presentation of
Systemic Lupus Erythematosus

Yiming Luo , Yumeng Wen, Ana Belen Arevalo Molina, Punya Dahal,
Lorenz Leuprecht, and Makda Bsrat
Department of Medicine, Mount Sinai St Luke’s and Mount Sinai West, Icahn School of Medicine at Mount Sinai, New York,
NY, USA

Correspondence should be addressed to Yiming Luo; [email protected]

Received 2 June 2018; Accepted 17 September 2018; Published 26 September 2018

Academic Editor: Fabrizio Conti

Copyright © 2018 Yiming Luo et al. This is an open access article distributed under the Creative Commons Attribution License,
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Macrophage activation syndrome (MAS) is a rare manifestation of systemic lupus erythematosus (SLE) with potentially life-
threatening consequences. To the best of our knowledge, this is the first case reported in literature for a constellation of MAS,
glomerulonephritis, pericarditis, and retinal vasculitis as initial presentation of SLE. Despite extensive multisystem involvement of
his disease, the patient responded well to initial steroid treatment, with mycophenolate mofetil successfully added as a steroid-
sparing agent. Our case highlights the importance of multispecialty collaboration in the diagnosis and management of SLE with
multisystem involvement.

1. Introduction initial presentation of systemic lupus erythematosus. Despite

the extensive involvement of his initial disease, the patient
Systemic lupus erythematosus (SLE) is a systemic auto- responded well to initial steroid treatment followed with
immune disorder which can involve almost all vital organs, mycophenolate mofetil.
including brain, eyes, heart, blood, and kidney [1]. The
clinical heterogeneity of the disease presents a consistent 2. Case Presentation
challenge to clinicians. The reported prevalence of sys-
temic lupus erythematosus (SLE) in the United States is A 37-year-old Caucasian male with a past medical history of
20 to 150 cases per 100,000, and the risk is higher among alcohol abuse was referred for inpatient admission after
Asians, African Americans, African Caribbean, and His- being found to have pancytopenia. He had subjective fever
panic Americans compared with Caucasian [2]. and productive cough with yellow sputum a few weeks ago,
Macrophage activation syndrome (MAS), also known as which resolved after a few days without treatment. He visited
hemophagocytic lymphohistiocytosis (HLH), is a rare and his primary care physician and laboratory exam showed
potentially fatal complication of several autoimmune dis- pancytopenia, thus leading to the referral. He also endorsed
eases, including juvenile idiopathic arthritis and SLE. The generalized weakness, progressive right eye blurry vision,
incidence of MAS associated with SLE is about 0.9–4.6% [3]. and chest tightness for the past few weeks. There was no skin
Excessive T-cell and macrophage activation and pro- rash, joint pain, hair loss, heartburn, and Raynaud’s phe-
liferation leads to hypercytokinemia and hemophagocytosis nomenon. Physical exam was only remarkable for cervical
and can result in overwhelming multisystem inflammatory nontender lymphadenopathy.
response [4]. Upon admission, he was febrile with a maximum
We report a rare case of a combination of MAS, glo- temperature of 101.2 F. Laboratory exam was notable for
merulonephritis, pericarditis, and retinal vasculitis as the white blood cell 1,900 counts/μL, hemoglobin 7.2 g/dL,
2 Case Reports in Medicine

hematocrit 21.2%, platelet 19,000 counts/μL, sodium underlying hematoimmunological response given his
126 mmol/L, and creatinine 1.44 mg/dL. Urinalysis showed overall clinical picture. And his grossly normal liver
elevated white blood cells, dysmorphic red blood cells, transaminase and bilirubin also make alcoholic hepatitis
and proteinuria. Further work up showed that he had ele- highly unlikely.
vated ferritin 6542 ng/mL, high triglycerides 327 mg/dL, The diagnosis of MAS in SLE can be challenging, as the
marked decreased complement levels (C3 14 mg/dL and presentation can mimic the clinical features of SLE or an
C4 3 mg/dL), elevated ESR 137 mm/hr, strongly positive for infectious complication. One recent study analyzed 89
antinuclear antibody (ANA, 1 : 640), and anti-double- adult SLE patients with MAS and found that MAS was the
stranded DNA antibody (anti-dsDNA, >1 : 1280). Anti- initial presentation of SLE in 46% [5], thus highlighting the
cardiolipin antibody (IgM and IgG) and beta-2 glycoprotein potentially crucial role of general internists or hospitalists
I antibody (IgG) were also positive. Direct antiglobulin test as they may first encounter such patients before rheuma-
(Coomb’s) was positive. Urine studies showed micro- tologists being involved. Hemophagocytosis is a late feature
albumin to creatinine ratio of 1958 mg/g and protein cre- of HLH, and a negative bone marrow biopsy does not
atinine ratio of 7.04 mg/mg consistent with nephrotic-range exclude the diagnosis of HLH/MAS [6]. Specific diagnostic
proteinuria. Transthoracic echocardiogram showed normal criteria for MAS in SLE are only proposed in pediatric
ventricular function but moderate circumferential pericar- population [7], but not in adult population. The well-
dial effusion. Abdominal ultrasonography showed hep- accepted HLH 2004 diagnostic criteria [8] and the pro-
atosplenomegaly with evidence of cirrhosis. Based on the posed 2009 diagnostic criteria [9] can be used, but they
above findings, he was diagnosed with systemic lupus were primarily developed for primary HLH. To aid the
erythematosus, pericarditis, and lupus nephritis. Pulse ste- diagnosis of secondary HLH in adult population, Fardet
roid with methylprednisolone 1000 mg daily was started for et al. developed the HScore [10], whose performance in
3 days, followed by oral prednisone 60 mg daily. His fever adult SLE population is unknown. Gavand recently ana-
and chest pain resolved, and his blood cell counts and lyzed 103 MAS episodes in 89 SLE adult populations and
creatinine improved after the treatment. He subsequently found that hyperferritinemia >500 µg/L had the best sen-
underwent bone marrow biopsy which showed increased sitivity (96.2%) and the strongest indicator to separate MAS
histiocytes with focal evidence of hemophagocytic cells from active SLE [5]. Interestingly, the study also demon-
consistent with macrophage activation syndrome considering strated significantly elevated procalcitonin in MAS epi-
his clinical presentation. Renal biopsy was also performed and sodes and could be considered as “red flag” for early
confirmed diffuse proliferative and membranous lupus ne- diagnosis in adult SLE patients without concomitant in-
phritis (Class IV/V) along with focal segmental glomerulo- fections [5]. Our patient fits into both HLH 2004 and 2009
sclerosis NOS type. He also underwent ophthalmology diagnostic criteria (fever, hepatosplenomegaly, pancyto-
evaluation, and funduscopic exam with fluorescein angio- penia, hyperferritinemia, hypertriglyceridemia, hypona-
gram showed cotton-wool spots with retinal hemorrhage tremia, and presence of hemophagocytosis on bone
consistent with retinal vasculitis. His laboratory examination marrow biopsy) and also with an HScore of 253, which
continued to improve, and he was subsequently discharged translates into a 99.5% probability of having HLH/MAS.
from hospital one week after admission. Mycophenolate The pathogenesis of MAS is not completely understood.
mofetil was started in addition to steroid upon discharge. The hallmark of the syndrome is characterized by excessive
Repeat transthoracic echocardiogram three weeks after activation and proliferation of macrophage and T-lym-
treatment showed marked decrease in pericardial effusions. phocytes, with massive release of proinflammatory cytokines
His disease remained stable while on mycophenolate mofetil [11]. Shimizu et al. [12] revealed a unique cytokine profile of
with prednisone gradually tapered from 60 mg to 10 mg SLE-MAS compared to systemic JIA-associated MAS and
twelfth week after discharge. His vision acuity remained EBV-induced HLH, with a pattern of a TNF-α dominant
stable, and repeat funduscopic examination showed im- increase and IgM-type antilymphocyte antibody detected on
provement of his retinal lesions. Detailed laboratory exami- the surface of lymphocytes during the acute phase and
nation in the hospital and on follow-up visit is presented in disappeared upon remission. Recent studies also suggested
Table 1. that increased serum-free IL-18 levels are causatively in-
volved in the MAS development [13].
3. Discussion There is no randomized controlled trial-based guideline
for managing MAS in patients with SLE. Steroid is the
We present a case of an adult male SLE patient with cornerstone of treatment [14]. Second immunosuppressive
multisystem involvement as initial presentation, including can be added in severe or refractory cases, including cy-
two rare and serious complications, MAS, and retinal clophosphamide [15], mycophenolate mofetil [16], ritux-
vasculitis. The diagnosis of SLE was confirmed by the imab [17], infliximab [18], anakinra [19], intravenous
presence of lupus nephritis on biopsy together with typical immunoglobulin [20], and plasma exchange [21]. HLH-2004
biochemical finding, including positive ANA, anti-dsDNA, treatment protocol with dexamethasone, cyclosporine, and
antiphospholipid antibodies, and low complement levels. etoposide can also be considered in selected cases [4]. Al-
Although a concomitant alcoholic hepatitis is essentially though MAS is considered a lethal complication of SLE,
difficult to exclude given his known history of alcohol recent studies showed that MAS in adult SLE popula-
abuse, his hepatosplenomegaly is more likely from his tion carried a better prognosis with mortality below 5%
Case Reports in Medicine 3

Table 1: Laboratory examination in the hospital and during follow-up visit.

6 weeks after 12 weeks after
Admission Discharge
discharge discharge
Blood count
Leukocyte (K/μL) 1.9 5.2 9.9 5.9
Hemoglobin (g/dL) 6.5 8 8.3 10.9
Hematocrit 19.2 23.7 26.3 32.5
Platelets (K/μL) 14 38 130 236
Chemistry
Sodium (mmol/L) 127 135 135 141
Potassium (mmol/L) 4.6 5.2 4.1 4.2
Chloride (mEq/L) 104 109 106 106
Bicarbonate (mmol/L) 21 22 22
Blood urea nitrogen (mg/mL) 23 43 29 16
Creatinine (mg/mL) 1.42 1.11 1.03 1.05
Glomerular filtration rate 56 75 81 79
Calcium (mg/mL) 5.8 7 7.6 8.4
Glucose (mg/mL) 100 88 130 76
Aspartate aminotransferase (U/L) 19 17 18
Alanine aminotransferase (U/L) 33 21 10
Alkaline phosphatase (U/L) 47 53 44
Total bilirubin (mg/dL) 0.2 0.2 0.2
Total protein (g/dL) 4.4 4.8 4.3 4.6
Albumin (g/dL) 1.4 1.5 2.3 2.4
Ferritin (ng/mL) 6542 1027 527 330
Lactate dehydrogenase (U/L) 336 252 275 187
Haptoglobin (mg/dL) <8 20 <8 52
Thyroid-stimulating hormone (uIU/mL) 7.5
Creatine kinase (U/L) 105
C-reactive protein (mg/L) 0.67
Vitamin B12 (pg/mL) 414
Triglycerides 327
Coagulation
Activated partial thromboplastin time (seconds) 31.5
Prothrombin time (seconds) 14.2
International normalized ratio 1.1
Dilute Russell’s viper venom time (seconds) 40.5
Others
Erythrocyte sedimentation rate (mm/hr) 137
Complement 3 (mg/dL) 14
Complement 4 (mg/dL) 3
Direct antiglobulin test, broad-spectrum Coomb’s
Positive
serum
Direct antiglobulin test, anti-IgG Coomb’s serum Positive
Direct antiglobulin test, anti-C3 Coomb’s serum Negative
Antibody identification Cold autoantibody
Urine study
Protein 3+ 3+ 1+ 1+
Protein/creatinine ratio 7.04
Blood 3+ 3+ 2+ 2+
Red blood cell (/HPF) 60 11–25 11–25
White blood cell (/HPF) 7 0–4 0–4
Autoimmune serology
Antinuclear antibody 1 : 640 (homogeneous pattern)
Anti-dsDNA antibody (IU/ml) 195
Anti-Ro antibody (AU/mL) 12
Anti-ribonucleoprotein antibody (AI) 0.5
Anti-Smith antibody (AI) 0.4
Anti-Scl 70 antibody (AI) 0.2
Rheumatoid factor (IU/mL) <15
Anti-cyclic citrullinated peptide antibody (units) 19
Anticardiolipin antibody, IgM (U/mL) 22
4 Case Reports in Medicine

Table 1: Continued.
6 weeks after 12 weeks after
Admission Discharge
discharge discharge
Anticardiolipin antibody, IgG (U/mL) 48
Anticardiolipin antibody, IgA (U/mL) <9
Beta-2 glycoprotein I antibody, IgM (GPI IgM units) <9
Beta-2 glycoprotein I antibody, IgG (GPI IgG units) 55
Beta-2 glycoprotein I antibody, IgA (GPI IgA units) 9

compared to other secondary HLH in historic cohort, and population and also the importance of multispecialty col-
steroid alone was sufficient in majority of the cases [5]. laboration in the diagnosis and management of SLE with
Retinal vasculitis in SLE, or lupus retinopathy, has been multisystem involvement.
found in 3 to 29% of patients with SLE. It often presents as
bilateral visual loss, correlates with SLE disease activity, and
is commonly associated with nephritis, central nervous
Conflicts of Interest
system involvement, and antiphospholipid antibodies [22]. All the authors declare that there are no conflicts of interest
Typical findings of lupus retinopathy in the fluorescein regarding the publication of this article.
angiography are tortuous retinal vessels, edema of papilla,
hemorrhagic, or cotton-wool spots. One recent study has
shown decreased survival in SLE patients with retinopathy References
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