Macrophage Activation Syndrome 

Updated: Nov 21, 2018
Author: Angelo Ravelli, MD; Chief Editor: Lawrence K Jung, MD 

Overview

Background

Macrophage activation syndrome (MAS) is a life-threatening complication of rheumatic disease that, for unknown reasons, occurs much more frequently in individuals with systemic juvenile idiopathic arthritis (SJIA) and in those with adult-onset Still disease.[1] Macrophage activation syndrome is characterized by pancytopenia, liver insufficiency, coagulopathy, and neurologic symptoms and is thought to be caused by the activation and uncontrolled proliferation of T lymphocytes and well-differentiated macrophages, leading to widespread hemophagocytosis and cytokine overproduction.[2, 3, 4, 5]

Pathophysiology

Macrophage activation syndrome is characterized by a highly stimulated but ineffective immune response. However, its pathogenesis is still poorly understood and has many similarities with that of the other forms of hemophagocytic lymphohistiocytosis (HLH). HLH is not a single disease but is a hyperinflammatory syndrome that can occur in association with various underlying genetic and acquired conditions. The best known form is familial HLH (FHLH), which is characterized by a severe impairment of lymphocyte cytotoxicity. Recent studies have shown that MUNC 13-4 polymorphisms are associated with macrophage activation syndrome in some patients with SJIA.[6]  A study by Weiss et al described a connection between MAS risk and interleukin-18 and suggests an interleukin-18 pathway and potential distinguishing biomarker and target of therapy.[7, 8]

 

The cytotoxic activity of natural killer (NK) and CD8+ T lymphocytes is mediated by the release of cytolytic granules, which contain perforin, granzymes, and other serinelike proteases, to the target cells. Several independent genetic loci related to the release of cytolytic granules have been associated with FHLH, and mutations at this level cause a severe impairment of cytotoxic function of NK cells and cytotoxic T lymphocytes (CTLs) in patients with FHLH. Through mechanisms that have not yet been well elucidated, this impairment in cytotoxic function leads to an excessive expansion and activation of cytotoxic cells, with hypersecretion of proinflammatory cytokines such as interferon (IFN)-γ, tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-10, and macrophage-colony-stimulating factor (M-CSF). These cytokines are produced by activated T cells and histiocytes that infiltrate all tissue and lead to tissue necrosis and organ failure.

In perforin-deficient mice, the animal model of HLH, infection with microorganisms such as lymphocytic choriomeningitis virus (LCMV) initiates a similar uncontrolled immune response. This immune response results in death and is characterized by fever, splenomegaly, hemophagocytosis, hypertriglyceridemia, and hypofibrinogenemia. Multiple cytokines, including IL-6, IL-18, IL-10, M-CSF, IFN-α and IFN-γ, are elevated; however, only the antibody to IFN-γ, and not the antibodies to other cytokines, prolongs survival and prevents the development of histiocytic infiltrates and cytopenia. Elevated IFN-γ is thought to be secondary to the increased antigen stimulation of CD8+ cells; neutralizing antibodies against LCMV lowers IFN-γ levels and prolongs survival.

These findings were supported by a recent study of hepatic biopsy samples in patients with various types of HLH, including macrophage activation syndrome.[9] The study revealed extensive infiltration of the liver by IFN-γ–producing CD8+ T lymphocytes and hemophagocytic macrophages secreting TNF-α and IL-6. The hyperproduction of IL-18, which strongly induces T helper cell 1 (Th-1) responses and IFN-γ production and enhances NK cells cytotoxicity, and an imbalance between levels of biologically active free IL-18 and levels of the IL-18–binding protein may also play a role in secondary hemophagocytic syndromes, including macrophage activation syndrome.[10]

Moreover, very high levels of IL-18 have been reported in 2 patients with SJIA and macrophage activation syndrome.[11] In a study of autopsy specimens of a child with SJIA–associated macrophage activation syndrome, the bone marrow was identified as the origin of increased serum IL-18.[12]

The mechanisms that lead to cytolytic defects in immunocompetent patients with acquired HLH are less clear. Patients with virus-associated HLH also have very low or absent cytolytic NK cell activity. However, in contrast to FHLH, this phenomenon appears to be related to a profoundly decreased number of NK cells rather than to impaired perforin expression. Notably, NK function has been found to completely recover in some patients after the resolution of the acute phase.[13]

Some evidence suggests that depressed NK activity, with or without abnormal perforin expression, may also be involved in the pathogenesis of SJIA–associated macrophage activation syndrome. Patients with active SJIA were found to have reduced perforin expression in NK cells and in cytotoxic CD8+ T lymphocytes compared with patients who had other subtypes of juvenile idiopathic arthritis and healthy control subjects.[14]

In some patients, decreased NK activity was associated with very low number of NK cells but mildly increased levels of perforin expression in NK cells and cytotoxic CD8+ T lymphocytes; this pattern was somewhat similar to that seen in virus-associated HLH. In other patients, very low NK activity was associated with only mildly decreased numbers of NK cells but very low levels of perforin expression in all cytotoxic cell types; this pattern was indistinguishable from that seen in primary HLH. Remarkably, most patients with low perforin expression had a history of multiple episodes of macrophage activation syndrome.

Decreased absolute numbers of NK cells, depressed NK cell cytolytic activity, or both may be a feature that distinguishes patients with SJIA from those with other forms of juvenile idiopathic arthritis.[15, 16] Whether these abnormalities will help identify the disease early in the course in patients who are more prone to the occurrence of this harmful complication remains to be seen.

Epidemiology

Frequency

United States

The exact incidence of macrophage activation syndrome in childhood rheumatic disorders is unknown.

International

Although considered a rare complication, macrophage activation syndrome is probably more common than previously thought. In a retrospective study from a tertiary care center, 7 of the 103 children (6.7%) diagnosed with SJIA over a 20-year period developed macrophage activation syndrome.[4] Approximately 100 cases have been reported in the literature.[2, 4, 17, 18]

Mortality/Morbidity

Macrophage activation syndrome is a complication of rheumatic disease that can follow a rapidly fatal course.

A study by Gormezano et al demonstrated that MAS occur in the majority of childhood systemic lupus erythematosus patients with acute pancreatitis with a higher mortality compared to adult systemic lupus erythematosus patients.[19]

Age

Macrophage activation syndrome generally develops in the earlier phases of the underlying disease or may be the presenting manifestation of SJIA; however, onset has been reported as long as 14 years after the initial diagnosis.[17] In most patients, primary disease is clinically active at the onset of macrophage activation syndrome; however, the syndrome may occasionally occur in a quiescent phase.

 

Presentation

History

The clinical presentation of macrophage activation syndrome (MAS) is generally acute and occasionally dramatic. Typically, patients become acutely ill with the sudden onset of nonremitting high fever, profound depression in all 3 blood cell lines (ie, leukopenia, anemia, and thrombocytopenia), hepatosplenomegaly, lymphadenopathy, and elevated serum liver enzyme levels. High levels of triglycerides and lactic dehydrogenase and low sodium levels are consistently observed.

The coagulation profile is often abnormal, with prolongation of prothrombin time (PT) and partial thromboplastin time (aPTT), hypofibrinogenemia, and detectable fibrin degradation products. In children with systemic juvenile idiopathic arthritis, the clinical picture may mimic sepsis or an exacerbation of the underlying disease. However, the pattern of nonremitting fever is different from the remitting high-spiking fever seen in systemic juvenile idiopathic arthritis. Moreover, patients may show a paradoxical improvement in the underlying inflammatory disease at the onset of macrophage activation syndrome, with disappearance of signs and symptoms of arthritis and a precipitous fall in the erythrocyte sedimentation rate. The latter phenomenon probably reflects the degree of hypofibrinogenemia secondary to fibrinogen consumption and liver dysfunction.[20]

Physical

Physical findings include the following:

  • Mucocutaneous findings

    • Purpura

    • Easy bruising

    • Mucosal bleeding

  • Hepatomegaly

  • Splenomegaly

  • Lymphadenopathy

  • CNS dysfunction

    • Lethargy

    • Irritability

    • Disorientation

    • Headache

    • Seizures

    • Coma

  • Other findings: Renal, pulmonary, and cardiac involvement have been reported in some patients.

Causes

Macrophage activation syndrome affects most commonly children with systemic juvenile idiopathic arthritis (SJIA) but has been observed in other rheumatic diseases, such as juvenile systemic lupus erythematosus (SLE)[21, 22] and Kawasaki disease[23] and, occasionally, polyarticular juvenile idiopathic arthritis.[17]

Although an identifiable precipitating factor is often not identified, macrophage activation syndrome has been related to numerous triggers, including a flare of the underlying disease, toxicity of aspirin or other nonsteroidal anti-inflammatory drugs (NSAIDs), viral infections, a second injection of gold salts, and sulfasalazine therapy.[5] One report described a young girl with SJIA who developed macrophage activation syndrome shortly after the first methotrexate (MTX) administration without any other apparent inciting factor; this suggests that macrophage activation syndrome could have been a direct consequence of MTX toxicity.[24]

The shortness of the time interval between MTX dosing and onset of macrophage activation syndrome (24 h) and the characteristics of clinical symptoms, particularly the intense and generalized itching, suggested hypersensitivity or an idiosyncratic reaction, a mechanism similar to that hypothesized in the pathogenesis of macrophage activation syndrome secondary to gold salt injections.

Recently, instances of macrophage activation syndrome in patients with SJIA during treatment with biologic medications, including tumor necrosis factor (TNF)-α inhibitors and interleukin (IL)-1 receptor antagonists, have been described. However, whether these drugs are responsible for the induction of macrophage activation syndrome is controversial.

Serious episodes of macrophage activation syndrome have been observed in patients who underwent autologous bone marrow transplantation for SJIA refractory to conventional therapy.[25, 26, 27, 28] In most of these cases, an infectious trigger for macrophage activation syndrome was identified; however, the complication was believed to be favored by stringent T-cell depletion, with resultant inadequate control of macrophage activation.[27, 29] After an adaptation of a protocol consisting of less profound T-cell depletion, better control of systemic disease before transplantation, and slow tapering of corticosteroids after the procedure, no further cases of macrophage activation syndrome have occurred.[27] The development of hemophagocytosis in 3 patients with SJIA who received fludarabine as part of the conditioning regimen has been reported.[26]

 

DDx

Diagnostic Considerations

Because macrophage activation syndrome (MAS) is a serious condition that can follow a rapidly fatal course, prompt recognition of its clinical and laboratory features and immediate therapeutic intervention are critical. However, because it lacks a single distinguishing characteristic and is clinically heterogeneous, early diagnosis can be difficult. Differential diagnosis between macrophage activation syndrome and a lupus flare or between macrophage activation syndrome and infections[30] , such as leishmaniasis may be particularly challenging.

Differential Diagnoses

  • Flare of underlying disease (eg, systemic juvenile idiopathic arthritis [SJIA], systemic lupus erythematosus [SLE])

  • Infection (eg, visceral leishmaniasis, brucellosis)

  • Sepsis

  • Side effects of medications

 

Workup

Laboratory Studies

The recognition that macrophage activation syndrome (MAS) is clinically similar to HLH has led many clinicians to use the diagnostic guidelines for hemophagocytic lymphohistiocytosis (HLH) in the diagnosis of macrophage activation syndrome.[31] However, the use of HLH criteria in patients with macrophage activation syndrome is associated with several problems; the chief problem is the requirement for tissue confirmation. A 2014 retrospective analysis concluded that HLH-2004 guidelines are likely not appropriate for identification of MAS in children with systemic juvenile idiopathic arthritis (SJIA), and that preliminary MAS guidelines showed the strongest ability to identify MAS in SJIA.[32]

The pathognomonic feature of the syndrome is bone marrow examination that reveals numerous well-differentiated macrophages actively phagocytosing hematopoietic cells. Such cells may be found in various other organs as well and may account for many of the systemic manifestations. However, in patients with HLH and macrophage activation syndrome, the bone marrow aspirate sample does not always reveal hemophagocytosis.[33] Furthermore, hemophagocytosis is not always demonstrable at onset. In HLH, hemophagocytosis may be detected more frequently in liver, lymph node, or splenic biopsy samples than in bone marrow samples. However, performing a biopsy of these organs is contraindicated in children with macrophage activation syndrome in the presence of intravascular coagulopathy. Moreover, the failure to document hemophagocytosis does not exclude the diagnosis of HLH. A 2014 study concluded that hyperinflammation, rather than hemophagocytosis, is the common link between macrophage activation syndrome andhemophagocytic lymphohistiocytosis.[34] These problems emphasize the need to identify criteria that obviate the need for tissue diagnosis.

To identify criteria for macrophage activation syndrome complicating systemic juvenile idiopathic arthritis (SJIA), the diagnostic sensitivity and specificity of the clinical and laboratory features of the syndrome were recently scrutinized.[18, 35, 36] Based on these results, preliminary diagnostic guidelines for macrophage activation syndrome complicating SJIA were established.

The diagnosis of macrophage activation syndrome requires the presence of any 2 or more the following laboratory criteria or 2 or more of the following clinical criteria:

  • Laboratory criteria

    • Decreased platelet count (< 262 x 109/L)

    • Elevated aspartate aminotransferase levels (>59 U/L)

    • Decreased WBC count (< 4 x 109/L)

    • Hypofibrinogenemia (≤2.5 g/L)

  • Clinical criteria

    • CNS dysfunction (eg, irritability, disorientation, lethargy, headache, seizures, coma)

    • Hemorrhages (eg, purpura, easy bruising, mucosal bleeding)

    • Hepatomegaly (≥3 cm below the costal margin)

  • Histopathologic criterion: Evidence of macrophage hemophagocytosis is found in the bone marrow aspirate sample. The demonstration of hemophagocytosis in bone marrow samples may be required in doubtful cases.

The above criteria are of value only in patients with active SJIA. The thresholds of laboratory criteria are provided only as an example. The clinical criteria are probably more useful as classification criteria rather than as diagnostic criteria because they often occur late in the course of macrophage activation syndrome and, therefore, may be of limited value in the early diagnosis of the syndrome.

Other abnormal clinical features in macrophage activation syndrome associated with SJIA not listed above include nonremitting high fever, splenomegaly, generalized lymphadenopathy, and paradoxical improvement of signs and symptoms of arthritis.

Other abnormal laboratory findings in macrophage activation syndrome associated with SJIA not listed above include anemia, a lowered erythrocyte sedimentation rate, elevated alanine aminotransferase levels, increased bilirubin levels, presence of fibrin degradation products, elevated lactate dehydrogenase levels, hypertriglyceridemia, low sodium levels, decreased albumin, and hyperferritinemia.

Because universally agreed on diagnostic criteria for macrophage activation syndrome complicating SJIA are not available, a multinational collaborative effort aimed to generate new criteria for diagnosing macrophage activation syndrome as a complication of SJIA is currently underway. The first step of the project has led to the identification of, by means of a Delphi survey, the clinical, laboratory and histopathologic features of macrophage activation syndrome that were felt to be most important by a large sample of international pediatric rheumatologists with experience with macrophage activation syndrome in children with SJIA.[37]

The diagnostic performance of potential criteria will be scrutinized further in the second phase of the study, through the analysis (ongoing) of real patient data. The final set of criteria is meant to be established in a consensus conference of experts using a combination of statistical and consensus formation techniques. The ultimate goal of the project is to develop a core set of criteria that is both highly sensitive and specific. These criteria will assist physicians in macrophage activation syndrome diagnosis in children with SJIA and enable quick institution of appropriate therapy.

As previously reported, diagnosis of macrophage activation syndrome may be particularly challenging in patients with systemic lupus erythematosus (SLE) because it may mimic the clinical and laboratory features of the underlying disease. Recently, preliminary diagnostic guidelines for macrophage activation syndrome complicating juvenile SLE were developed.[38]

The main laboratory findings of macrophage activation syndrome include the following:

  • Cytopenias

  • Abnormal serum hepatic enzyme levels

  • Coagulopathy

  • Decreased erythrocyte sedimentation rate

  • Hypertriglyceridemia

  • Hyponatremia

  • Hypoalbuminemia

  • Hyperferritinemia

The initial laboratory evaluation should include the following:

  • CBC count with platelets and reticulocyte count

  • Acute phase reactants (ie, erythrocyte sedimentation rate and C-reactive protein [CRP] levels)

  • Markers of liver and kidney function

  • Ferritin levels: Hyperferritinemia is an important laboratory hallmark of macrophage activation syndrome that has received increasing attention; elevated ferritin levels (often >10,000 ng/mL) have been reported in the acute phase of macrophage activation syndrome. Furthermore, a good correlation between ferritin levels and response to therapy has been observed; a decrease in ferritin levels is associated with a favorable course of macrophage activation syndrome. Recent studies have shown that low levels of glycosylated ferritin, in the presence of high level of total serum ferritin, may be another helpful marker for diagnosis.[39, 40]  A retrospective analysis by Ruscitti et al that included 50 Still’s disease patients (21 pediatric and 29 adult) reported that at diagnosis, high levels of serum ferritin and an elevated systemic score were associated with MAS.[41]  

Other Tests

Recently, gene expression profiling and determination of sIL-2R alpha and sCD163 concentration in peripheral blood have been suggested as useful tools for identifying early macrophage activation syndrome in patients with SJIA.[42, 43] However, the routine use of these diagnostic techniques outside of a research context is still unavailable in most laboratories worldwide.

Histologic Findings

The pathognomonic feature of the syndrome is bone marrow examination that reveals numerous well-differentiated macrophages actively phagocytosing hematopoietic cells. Such cells may be found in various other organs, as well, and may account for many of the systemic manifestations. However, in patients with macrophage activation syndrome, the bone marrow aspirate does not always show hemophagocytosis. Moreover, failure to reveal hemophagocytosis does not exclude the diagnosis of macrophage activation syndrome.

 

Treatment

Medical Care

The treatment of macrophage activation syndrome (MAS) is traditionally based on the parenteral administration of high doses of corticosteroids. However, some fatalities have been reported, even among patients treated with massive doses of corticosteroids.[2, 4, 17] The administration of high-dose intravenous immunoglobulins, cyclophosphamide, plasma exchange, and etoposide has provided conflicting results.

The use of cyclosporin A (CyA) was considered based on its proven benefit in the management of familial hemophagocytic lymphohistiocytosis (FHLH). CyA was found to be effective in severe or corticosteroid-resistant macrophage activation syndrome.[21, 44, 45] In some patients, this drug exerted a “switch-off” effect on the disease process, leading to quick disappearance of fever and improvement of laboratory abnormalities within 12-24 hours.[21] Because of the distinctive efficacy of CyA, some authors have proposed using this drug as the first-line treatment for macrophage activation syndrome occurring in childhood systemic inflammatory disorders.[21, 44]

Increased production of tumor necrosis factor (TNF) in the acute phase of macrophage activation syndrome has suggested the use of TNF-α inhibitors as potential therapeutic agents. However, although Prahalad et al reported the efficacy of etanercept in a boy who developed macrophage activation syndrome,[46] other investigators have observed the onset of macrophage activation syndrome in patients with systemic juvenile idiopathic arthritis (SJIA) who were treated with etanercept.[46, 47] Similarly, Lurati et al reported the onset of macrophage activation syndrome in a patient with systemic juvenile idiopathic arthritis during treatment with the recombinant interleukin (IL)-1 receptor–antagonist anakinra.[48] Macrophage activation syndrome has also been reported in a patient with adult-onset Still disease who was receiving anakinra.[49]

Although the association between macrophage activation syndrome onset and treatment with etanercept or anakinra may be coincidental and not causal, the above-mentioned observations suggest that inhibition of tumor necrosis factor (TNF) or IL-1 does not prevent macrophage activation syndrome. Moreover, although macrophage activation syndrome–like symptoms are almost completely prevented by elimination of CD8+ T cells or by neutralization of INF-λ in perforin-deficient mice, the animal model of hemophagocytic lymphohistiocytosis (HLH), inhibition of IL-1 or TNF provides only mild alleviation of the symptoms.

Despite these observations, several cases of SJIA-associated macrophage activation syndrome dramatically benefiting from anakinra after inadequate response to corticosteroids and cyclosporin have now been reported.[50, 51, 52, 53, 54, 55] For those severely ill children, IL-1 blockade has been remarkably effective in a relative brief time frame.

Other forms of HLH not associated with rheumatic diseases usually require more aggressive treatment: for instance, children younger than 1 year in whom FHLH is suspected and all patients with severe signs and symptoms are candidates for combination therapy with dexamethasone, cyclosporin A, and etoposide. Etoposide has been shown to improve prognosis for Epstein-Barr virus (EBV)–related HLH; its effectiveness may be explained by inhibition of synthesis of EBV nuclear antigen. Whether HLH therapeutic protocols are suitable for use in children with macrophage activation syndrome associated with rheumatic diseases is unclear.

Despite aggressive treatment, long-term disease-free survival in patients with FHLH can be reached only after stem cell transplantation.[56]

Consultations

Multiple subspecialists are often needed to manage a patient with macrophage activation syndrome and may include rheumatologist, hematologist/oncologist, infectious disease specialist, intensivist, and others.

A study looked for insights into the heterogeneity of macrophage activation syndrome (MAS) complicating systemic juvenile idiopathic arthritis (sJIA) through the analysis of a large patient sample collected in a multinational survey. The study found that patients seen in North America were given biologics more frequently. Patients entered by pediatric hemato-oncologists were treated more commonly with biologics and etoposide, whereas patients seen by pediatric rheumatologists more frequently received cyclosporine. The study underscores the need to establish uniform therapeutic protocols.[57]

 

Medication

Corticosteroids

Class Summary

These agents decrease inflammatory response.

Prednisone (Deltasone, Meticorten, Orasone)

Immunosuppressant for treatment of autoimmune disorders; may decrease inflammation by reversing increased capillary permeability and suppressing PMN activity. Stabilizes lysosomal membranes and also suppresses lymphocyte and antibody production.

Methylprednisolone (Solu-Medrol)

Decreases inflammation by suppressing migration of PMN leukocytes and reversing increased capillary permeability.

Immunomodulator

Class Summary

Calcineurin inhibitors (eg, cyclosporine) inhibit IL-2, which is essential for T-cell proliferation.

Cyclosporine (Neoral)

An 11-amino acid cyclic peptide and natural product of fungi. Acts on T-cell replication and activity. Specific modulator of T-cell function and an agent that depresses cell-mediated immune responses by inhibiting helper T-cell function. Preferential and reversible inhibition of T lymphocytes in G0 or G1 phase of cell cycle suggested.

Binds to cyclophilin, an intracellular protein, which, in turn, prevents formation of IL-2 and the subsequent recruitment of activated T cells. Has approximately 30% bioavailability, but widely varies on an individual level. Specifically inhibits T-lymphocyte function with minimal activity against B cells. Maximum suppression of T-lymphocyte proliferation requires that drug be present during first 24 h of antigenic exposure.

Suppresses some humoral immunity and, to a greater extent, cell-mediated immune reactions (eg, delayed hypersensitivity, allograft rejection, experimental allergic encephalomyelitis, and graft-vs-host disease) in various organs.

 

Follow-up

Further Outpatient Care

After the resolution of macrophage activation syndrome, the underlying disease should be monitored at follow-up periodic visits.

Further Inpatient Care

Because macrophage activation syndrome (MAS) may be a life-threatening complication, care in an ICU may be warranted.

Transfer

Transfer should be considered if appropriate level of care is not available locally.

Complications

Sepsis is an important complication due to the profound depression of WBCs. The abnormal coagulation profile may lead to hemorrhagic manifestations like purpura, easy bruising and mucosal bleeding.

Prognosis

The prognosis is related to the severity of CNS, renal, pulmonary or cardiac involvement.

 

Questions & Answers

Overview

What is macrophage activation syndrome (MAS)?

What is the pathophysiology of macrophage activation syndrome (MAS)?

What is the US prevalence of macrophage activation syndrome (MAS)?

What is the global prevalence of macrophage activation syndrome (MAS)?

What is the mortality and morbidity associated with macrophage activation syndrome (MAS)?

Which age groups have the highest prevalence of macrophage activation syndrome (MAS)?

Presentation

Which clinical history findings are characteristic of macrophage activation syndrome (MAS)?

Which physical findings are characteristic of macrophage activation syndrome (MAS)?

What causes macrophage activation syndrome (MAS)?

DDX

Which conditions are included in the differential diagnoses of

What are the differential diagnoses for Macrophage Activation Syndrome?

Workup

How is macrophage activation syndrome (MAS) diagnosed?

How is macrophage activation syndrome (MAS) complicating systemic juvenile idiopathic arthritis (SJIA) diagnosed?

How is macrophage activation syndrome (MAS) diagnosed in patients with systemic lupus erythematosus (SLE)?

What is the role of genetic analysis in the workup of macrophage activation syndrome (MAS)?

Which histologic findings are characteristic of macrophage activation syndrome (MAS)?

Treatment

How is macrophage activation syndrome (MAS) treated?

Which specialist consultations are beneficial to patients with macrophage activation syndrome (MAS)?

Follow-up

What is included in the long-term monitoring of macrophage activation syndrome (MAS)?

When is inpatient care indicated for macrophage activation syndrome (MAS)?

When is patient transfer required for the treatment of macrophage activation syndrome (MAS)?

What are the possible complications of macrophage activation syndrome (MAS)?

What is the prognosis of macrophage activation syndrome (MAS)?

Medications

Which medications in the drug class Immunomodulator are used in the treatment of Macrophage Activation Syndrome?

Which medications in the drug class Corticosteroids are used in the treatment of Macrophage Activation Syndrome?