Reactive Macrophage Activation Syndrome Research Articles

Clinical spectrum and therapeutic management of systemic lupus erythematosus-associated macrophage activation syndrome: a study of 20 Moroccan adult patients.

The objective of this study was to describe the clinical and laboratory manifestations, triggers factors, treatment, and outcome of MAS complicating SLE. We retrospectively analyzed the medical records of adult patients with SLE for a period of 8years (2009-2016) and identified patients who had developed MAS. We conducted statistical analysis to identify factors associated with MAS. Among 208 consecutive lupus patients, 20 patients (19 women) were identified having MAS. The mean age of patients was 35.4 ± 10years. MAS revealed lupus in 7 patients. In the others, the delay between diagnosis of SLE and MAS was 33,3months. All cases required hospital admission, and 2 patients were admitted to the intensive care unit. An anemia (hemoglobin < 10g/dL) was found in all patients. A thrombopenia was observed in 19 (95%) cases. Hypertriglyceridemia and hyperferritinemia were present in all patients. All patients had anti-nuclear antibodies and anti-double-stranded DNA antibodies. Bone marrow aspiration showed hemophagocytosis in 15 (94%) cases. The mean SLEDAI was 20.95 corresponding to an SLE of a very high activity. The mean H-Score was 233.85. MAS was associated with a lupus flare in 13 patients. Documented bacterial infections, viral infections, and a breast cancer were respectively diagnosed in 4, 3, and 1 cases respectively. The corticosteroids were administered in all patients. Intravenous cyclophosphamide was used together with corticosteroids in 6 patients, mycophenolate mofetil in 2 cases and azathioprine in 2 cases. Intravenous immunoglobulin was given in 4 cases, etoposide in one case and rituximab was used as the third line treatment in one patient. All infectious episodes were also treated by broad spectrum antibiotics. All patients had a good outcome without any mortality at the management, with a mean follow-up of 24months. The clinical parameters significantly associated with MAS were fever (p = 0,001), splenomegaly (p < 0.0001), lymphadenopathy (p < 0.0001), oral and/or nasopharyngeal ulceration (p = 0.04), arthritis (p = 0.017), and pulmonary signs (p = 0.003). Laboratory parameters associated with MAS were anemia (p < 0.0001), thrombopenia (p < 0.0001), hyperferritinemia (p < 0.0001), hypertriglyceridemia (p < 0.0001), SLEDAI (p < 0.0001), and H-Score (p < 0.0001). Receiver operating characteristic (ROC) analysis identified optimal cutoff values of ferritin (> 695ng/mL) and SLEDAI (> 13.5) to predict the occurrence of MAS in SLE. MAS was observed in 9.62% Moroccan adult patients with SLE. SLE flare and infection were the common triggers of MAS in our study. Our study indicates that the occurrence of unexplained fever, splenomegaly, lymphadenopathy, profound cytopenia, hyperferritinemia, hypertriglyceridemia, high SLEDAI, and H-Score should raises the possibility of the diagnosis of MAS in SLE patients. Early diagnosis and urgent therapeutic management improves the overall prognosis. Key Points • Macrophage activation syndrome (MAS) is an underdiagnosed complication of systemic lupus erythematosus (SLE). The prevalence of this complication in this study is nearly 10%. • The diagnosis of MAS represents a major challenge for clinicians, as it could mimic a SLE flare up or be confused with infections. Validated diagnostic criteria for MAS in adults secondary to SLE are urgently needed. • In this study, the H-score calculate the individual risk of adult patients having reactive MAS. The cut-off value for the H-score was 190.5 (sensitivity 96.7%, specificity 97.6%). • The prognosis of MAS with SLE is good in our study. However, in the literature MAS may be a fatal condition in SLE patients. Prospective studies are necessary to confirm these results.

Macrophage activation syndrome complicating adult-onset still's disease: A diagnostic challenge

We report the case of a young man who presented with high-spiking fever, erosive arthritis, and generalized lymphadenopathy. He was diagnosed as adult-onset Still's disease (AOSD), and his clinical course was complicated by reactive macrophage activation syndrome (MAS). The sudden precipitous drop in leukocyte and platelet counts proved a valuable clue to the diagnosis of MAS in the setting of AOSD. The new American College of Rheumatology/European League Against Rheumatism classification criteria for reactive MAS complicating systemic juvenile idiopathic arthritis were applied in this patient. When MAS is associated with AOSD, treatment could be challenging. We managed this patient successfully with a combination of systemic corticosteroids and cyclosporine in the acute phase.

Reactive macrophage activation syndrome possibly triggered by canakinumab in a patient with adult-onset Still's disease

Macrophage activation syndrome (MAS) is a rare and serious complication of adult-onset Still's disease. We describe a case in a 49-year-old woman with Still's disease refractory to glucocorticoids, methotrexate, and infliximab. Anakinra provided satisfactory disease control for 1year, after which escape phenomenon occurred. After four tocilizumab injections, cutaneous melanoma developed. The persistent systemic manifestations prompted treatment with two canakinumab injections. Ten days later, she had a spiking fever, dyspnea, low back pain, abdominal pain, odynophagia, and hepatomegaly. Laboratory tests showed liver cytolysis (180IU/L; N: 10–35), acute renal failure (creatinine, 407μmol/L; N:50–100), thrombocytopenia (60G/L; N: 150–400), leukocytosis (12,200/mm3; N: 4000–10,000), hypertriglyceridemia (5070mmol/L; N: 0.4–1.6), lactate dehydrogenase elevation (4824IU/L; N: 135–250), and hyperferritinemia (97 761μg/L; N:15–150). Examination of a bone marrow biopsy showed phagocytosis. Tests were negative for viruses and other infectious agents. Glucocorticoid therapy (1.5mg/Kg/d) and intravenous polyvalent immunoglobulins (0.5g/Kg/d) were given. Her condition improved despite the many factors of adverse prognostic significance (thrombocytopenia, absence of lymphadenopathy, and glucocorticoid therapy at diagnosis). This is the first reported case of MAS after canakinumab therapy in a patient with adult-onset Still's disease.

Macrophage activation syndrome triggered by primary disseminated toxoplasmosis

We report the case of a patient with disseminated toxoplasmosis who presented with cervical lymphadenopathies and pneumonia. Although the infection was successfully treated with co-trimoxazole, the patient developed reactive macrophage activation syndrome (rMAS). To our knowledge, this is the first reported case of rMAS triggered by toxoplasmosis in the medical literature.

RE: Reactive macrophage activation syndrome (MAS) in a patient with parvovirus B19 infection, lymphocytic lichenoid vasculitis, urticaria and angioedema

lettersRE: Reactive macrophage activation syndrome (MAS) in a patient with parvovirus B19 infection, lymphocytic lichenoid vasculitis, urticaria and angioedema Luis Gonzalez-Granado Luis Gonzalez-Granado Search for more papers by this author Published Online:3 Jun 2010https://doi.org/10.4103/0256-4947.62827SectionsPDF ToolsAdd to favoritesDownload citationTrack citations ShareShare onFacebookTwitterLinked InRedditEmail AboutIntroductionTo the Editor: I read with keen interest the article published by Soldo-Juresa et al in the last issue of the journal.1 I would like to make some comments: First, Still disease should be kept in mind whenever macrophage activation syndrome is considered in a patient with the clinical picture shown. In fact the patient's condition fulfills the criteria published by Yamagushi for Still disease.2 I would like to remark that the measurement of soluble IL-2R (also known as CD25s) could be helpful in distinguishing between Still disease and MAS.3 Furthermore, the development of MAS in Still disease is not infrequent and intravenous gamma globulins have shown promising results in treatment.4,5 Second, as the authors rule out a C1q-linked vasculitis, C4 and alternative complement pathway activity should be measured. It is well known that in esterase inhibitor type II levels of C1-inhibitor esterase are normal although C4 is decreased due to low functional C1-inhibitor levels.6 Hypocomplementemic vasculitis has been also described in patients with factor I deficiency.7 I have attended recently a patient with vasculitis secondary to factor I deficiency. This factor was not measured by the author in this patient. Third, the authors recognize that DNA of parvovirus B-19 can persist in bone marrow for years. This is why we should distinguish between MAS secondary to viral infection or underlying Still disease that needs long-term treatment and follow-up.ARTICLE REFERENCES:1. Soldo-Juresa D, Radman M, Pejsa V, Bozikov V. "Reactive macrophage activation syndrome in a patient with parvovirus B19 infection, lymphocytic lichenoid vasculitis, urticaria and angioedema" . Ann Saudi Med. 2010; 30:88-9. Google Scholar2. Yamaguchi M, Ohta A, Tsunematsu T, Kasukawa R, Mizushima Y, Kashiwagi H, Kashiwazaki S, Tanimoto K, Matsumoto Y, Ota T. "Preliminary criteria for classification of adult Stills disease" . J Rheumatol. 1992; 19:424-430. Google Scholar3. Bleesing J, Prada A, Siegel DM, Villanueva J, Olson J, Ilowite NT, Brunner HI, Griffin T, Graham TB, Sherry DD, Passo MH, Ramanan AV, Filipovich A, Grom AA. "The diagnostic significance of soluble CD163 and soluble interleukine-2 receptor a -chain in macrophage activation syndrome and untreated new-onset systemic juvenile idiopathic arthritis" . Arthritis Rheum. 2007; 56:965-71. Google Scholar4. García-Consuegra Molina J, Merino Muñoz R, de Inocencio Arocena J. "Grupo de Estudio del Síndrome de Activación Macrofágica y Artritis Idiopática Juvenil de la Sociedad Española de Reumatología Pediátrica. Macrophage activation syndrome and juvenile idiopathic arthritis. A multicenter study" . An Pediatr (Barc). 2008; 68:110-6. Google Scholar5. Vignes S, Wechsler B, Amoura Z, Papo T, Francès C, Huong DL, Veyssier P, Godeau P, Piette JC. "Intravenous immunoglobulin in adult Still's disease refractory to non-steroidal anti-inflammatory drugs" . Clin Exp Rheumatol. 1998; 16:295-8. Google Scholar6. Zuraw BL, Christiansen SC. "Pathogenesis and laboratory diagnosis of hereditary angioedema" . Allergy Asthma Proc. 2009; 30:487-92. Google Scholar7. Sadallah S, Gudat F, Laissue JA, Spath PJ, Schifferli JA. "Glomerulonephritis in a patient with complement factor I deficiency" . Am J Kidney Dis. 199906 33(6):1153-7. Google Scholar Previous article Next article FiguresReferencesRelatedDetails Volume 30, Issue 3May–Jun 2010 Metrics History Published online3 June 2010 InformationCopyright © 2010, Annals of Saudi MedicineThis is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.PDF download

Increased serum vitamin B 12 levels are associated with adult-onset Still's disease with reactive macrophage activation syndrome

Background Adult-onset Still's disease (AOSD) can be complicated by reactive macrophage activation syndrome (rMAS). The objective of this study was to evaluate vitamin B 12 values in AOSD with and without rMAS. Methods All patients’ files with AOSD in one center were retrospectively reviewed. Hemophagocytosis was defined as phagocytosis of various hematopoietic cells by macrophages. Clinical data including fever, rash, sore throat, arthritis, lymphadenopathy were recorded. Laboratory tests included complete blood count, serum ferritin, transaminases, serum triglyceride and vitamin B 12 level. The control group was selected from our AOSD pool who had AOSD without rMAS. Results Seven patients (5 female) had AOSD with rMAS. Median age at the diagnosis of rMAS was 32 (range, 27–37) and median follow-up duration after rMAS diagnosis was 18 months (range, 2–60). All of the patients with rMAS had fever, sore throat, rash, arthritis, anemia and hyperferritenemia. Five of seven patients had hepatosplenomegaly and lymphadenopathy. Four of seven patients had normal or low leucocyte count, three of seven patients had increased triglyceride level. The patients with AOSD and rMAS mean ± standard deviation (S.D.) vitamin B 12 levels were significantly higher than without rMAS (1903 ± 960 vs 542 ± 328 pg/ml, p = 0.001). The specificity (75%) of increased vitamin B 12 level was high and sensitivity (100%) was excellent. Conclusion Elevated vitamin B 12 levels seems to be a good marker for diagnostic marker in AOSD when complicated with rMAS.

Reactive macrophage activation syndrome in a patient with parvovirus B19 infection, lymphocytic lichenoid vasculitis, urticaria and angioedema.

47-year-old woman had a history of episodic acute intermittent angioedema and urticaria with moderate pruritus for one month. She was on 10 mg of loratadine daily. She had a fever of 39oC, arthralgia, fatigue, and angioedema of the upper respiratory tract. Laboratory results are shown in [Table 1]. She had elevated IgE (206 kU/L). The immunoassay for C1-esterase inhibitor was normal. She was treated with H1- and H2-blocking antihistamines, and methylprednisolone intravenously (1 mg/kg/day). Culture results and viral titers were negative except for a high positive titer of specific IgG antibody to parvovirus B19 of 11.1 (positive titer >1). On the third week of hospitalization, she deteriorated rapidly and developed a macular rash on the trunk and extremities with generalised lymphadenpathy, liver dysfunction and disseminated intravascular coagulopathy (DIC) [Figure 1]. A skin biopsy specimen was compatible with lymphocytic lichenoid vasculitis. An inflammatory pattern centered on the basal layer of the epidermis and upper dermis in a dense band-like distribution. Direct immunofluorescence showed no IgG, IgA, IgM, C3, C1q and fibrinogen deposits. A bone marrow aspirate showed hemophagocytosis [Figure 2]. Parvovirus B19 DNA was detected by the polymerase chain reaction (PCR) in bone marrow [Figure 3]. Macrophage activation syndrome was confirmed. The patient was treated with methylprednisolone 250 mg/day intravenously and intravenous immunoglobulin (IVIG) 0.55 g/kg BW/day for five consecutive days, followed by methylprednisolone 1 mg/kg daily. Fresh frozen plasma and enoxaparin were administered. Two days after treatment, she improved. Monthly infusions of IVIG were continued for 6 months. Corticosteroids were tapered gradually to 8 mg of methylprednisolone daily. On periodic follow-up, the patient was quite well without episodes of angioedema and no new skin lesions were seen. Our patient met all criteria for reactive macrophage activation syndrome (rMAS) outlined by Imashuku. [1] Acute parvovirus B19 infection can be diagnosed by demonstrating a four-fold rise in serum B19-specific IgG antibody titers, as in our case. B19 specific DNA or antigens can be detected for months or even years after infection. [2], [3] We speculate that the presence of acute parvovirus B19 infection was a trigger for rMAS. [4] Lymphocytic vasculitis is a reactive process. [5], [6] Purpura pigmentosa chronica, fixed drug eruption, urticarial vasculitis, allergic vasculitis, and the vasculitis of Sjogren syndrome are known to have lymphocytic vasculitis. We conclude that rMAS might represent a subgroup of patients with systemic inflammatory response amenable to IVIG treatment. Given early, IVIG may interrupt the processes that lead to macrophage overactivation.

Reactive macrophage activation syndrome in a patient with parvovirus B19 infection, lymphocytic lichenoid vasculitis, urticaria and angioedema

Reactive macrophage activation syndrome in a patient with parvovirus B19 infection, lymphocytic lichenoid vasculitis, urticaria and angioedema