Diagnosis Of Macrophage Activation Syndrome Research Articles

Macrophagic activation syndrome complicating miliary tuberculosis: A case report

Macrophage activation syndrome (MAS), also known as hemophagocytic syndrome or lymphohistiocytic activation syndrome, is a rare but potentially fatal disease. It results from inappropriate stimulation of macrophages in the bone marrow and lymphoid organs. The diagnosis of MAS is based on a combination of clinical, biological, and histological or cytological signs. MAS is categorized into primary forms, which mainly affect newborns and infants with a family history, and secondary forms, which occur in the context of neoplastic, autoimmune, or infectious diseases. Treatment involves addressing the specific causative agent of MAS and, in certain cases, early administration of corticosteroids and immunoglobulins. MAS is rarely associated with tuberculosis. We report the case of an immunocompetent patient presenting with miliary tuberculosis complicated by macrophage activation syndrome.

Macrophage activation syndrome with acute hepatitis in a patient with adult-onset immunodeficiency with anti-interferon gamma antibodies: a case report

BackgroundMacrophage activation syndrome is a rare disorder leading to unregulated immune activity manifesting with nonspecific constitutional symptoms, laboratory abnormalities, and multiorgan involvement. We report the case of a patient who presented with acute hepatitis secondary to macrophage activation syndrome diagnosed by liver biopsy and successfully treated with intravenous immune globulin, anakinra, and rituximab.Case presentationA 42-year-old Laotian woman with adult-onset immunodeficiency with anti-interferon gamma antibodies presented with a fever, headache, generalized myalgia, dark urine, and reduced appetite in the setting of family members at home with similar symptoms. Her laboratory workup was notable for evidence of acute hepatitis without acute liver failure. After an unrevealing comprehensive infectious and noninvasive rheumatologic workup was completed, a liver biopsy was performed ultimately revealing the diagnosis of macrophage activation syndrome. She was successfully treated with intravenous immune globulin, anakinra, and rituximab.ConclusionThis case highlights the importance of maintaining macrophage activation syndrome on the differential of a patient with acute hepatitis of unknown etiology in the correct clinical context and the value of a liver biopsy in making a diagnosis when noninvasive testing is unrevealing.

Systemic Lupus Erythematosus and Cytokine Storm.

Systemic lupus erythematosus (SLE) is the prototype of autoimmune diseases and can manifest with a plethora of clinical signs and symptoms associated with a myriad of laboratory abnormalities. An infrequent but potentially lethal complication of SLE is macrophage activation syndrome (MAS). The diagnosis of MAS in SLE can be very challenging due to similarities in presentation of both flares and infections, such as fever, lymphadenopathy, splenomegaly, and cytopenias. These aggravating factors contribute to the increased risk of poor outcomes in SLE-associated MAS. Indeed, at the moment MAS remains invariably lethal if untreated and still has a high mortality rate with treatment. In this chapter, we discuss several aspects of MAS in the context of SLE and in particular, the pathogenesis of MAS in SLE, how MAS presents in pediatric versus adult SLE, and, finally, MAS treatment in SLE and future directions.

MACROPHAGIC ACTIVATION SYNDROME IN POST KIDNEY TRANSPLANTATION REVEALED BY PERITONITIS: CASE REPORT

Objective: Macrophage activation syndrome is a rare but potentially fatal condition. The diagnosis is often difficult, because the symptoms are not very specific and can mimic those of sepsis, however, its diagnosis is based on the association of clinical and biological, non-specific signs, coupled with cytological or histological research of hemophagocytosis and an exhaustive etiological investigation. Design and method: We report the case of a 40-year-old man with a history of chronic renal failure of undetermined origin, who received a kidney transplant in 2011 from a living related donor. The clinical objective shows signs of dehydration associated with non-fetid diarrhea with the presence of a tense and sensitive abdomen on palpation evoking a surgical abdomen, all evolving in a febrile context; Haematological involvement such as bicytopenia and a positive CMV PCR. Our patient was operated on urgently for peritonitis, after performing peritoneal cleansing, the surgeon took biopsy samples from the various mesenteric lymph nodes. Results: The diagnosis of Macrophage activation syndrome is made in the face of clinical and biological arguments in favor, the histological study of the mesenteric lymph nodes revealing non-Langerhancan lymph node histiocytosis CD 68 + CD 10 evoking a syndrome of macrophage activation and confirmed by the myelogram Conclusions: Much progress remains to be made in the field of SAM in adults, the severity of its prognosis, essentially in a kidney transplant patient, requires an aggressive diagnostic approach and multidisciplinary therapeutic management.

P19 A case of pyrexia of unknown origin - wrong way round!

P19 A case of pyrexia of unknown origin - wrong way round!

33372 A case of systemic lupus erythematous presenting with macrophage activation syndrome

A 36-year-old male with no significant medical history presented with at least 1 month of intermittent fevers, diffuse arthralgias, malaise, and weakness. During this timeframe, he was treated for possible infectious etiologies without clinical improvement. Ultimately, he was admitted after his wife found him unable to converse normally. Initial workup revealed hyperferritinemia (>40,000), elevated anti-dsDNA serologies, and other diagnostic criteria consistent with acute systemic lupus erythematous (SLE). Dermatology was consulted as well as Rheumatology and Nephrology. On examination, there were scaly, red/violaceous papules and plaques in a photodistribution most prominent over the malar cheeks, forehead, and ears. In addition, there were numerous follicularly-based vesicles over all four extremities and tender erythematous macules involving the palms and soles. Two punch biopsies were obtained (one for H&E and one for immunofluorescence (IF)) which illustrated an intense vacuolar interface dermatitis with dyskeratotic epidermal cells, but a negative IF study. Nephrology performed a renal biopsy which revealed a “full house” staining (IgM, IgG, IgA, C3, and C1q all positive) on IF confirming the diagnosis of lupus. The patient was started on high-dose steroids, hydroxychloroquine, and mycophenolate mofetil with minimal improvement. After discussion with Hematology, a bone marrow biopsy was performed which revealed evidence of hemophagocytosis confirming a diagnosis of macrophage activation syndrome. After prolonged high-dose corticosteroids coupled with other therapies, the patient’s clinical picture improved. We present this patient to highlight a rare complication of SLE as well as underscore the importance of collaborative efforts between different specialties in improving patient outcomes.

Assessment of MS-Score and HScore in timeliness of diagnosis of macrophage activation syndrome associated with adult-onset Still's disease

The data of 33 patients with adult-onset still's disease (AOSD)-associated macrophage activation syndrome (MAS) were retrospectively collected from January 2013 to December 2020 in Peking Union Medical College Hospital. Hemophagocytic lymphohistiocytosis (HLH)-2004 criteria, macrophage activation syndrome/juvenile idiopathic arthritis (MS-Score) and hemophagocytic syndrome diagnostic score (HScore) were used to diagnose AOSD-associated MAS, respectively. The time of diagnosis of AOSD-associated MAS by MS-Score was 19.0 (4.5, 31.0) days [M (Q1,Q3)] earlier than by HLH-2004 criteria, and 13.5 (0.5, 21.5) days earlier than by HScore (both P<0.05). The difference was not statistically significant between the time of diagnosis of AOSD-associated MAS by Hscore and by HLH-2004 criteria (P>0.05). There was significant difference among the three criteria (P<0.001). MS-Score can be used to diagnose AOSD-associated MAS earlier than HLH-2004 criteria, while the timeliness of HScore is not certain.

Necrotising sinusitis with orbital complication in patient with macrophage activation syndrome (MAS)

Background: Macrophage activation syndrome (MAC) is a potentially fatal clinical-laboratory syndrome of uncontrolled hyperinflammation arising as a result of hereditary or acquired immune-mediated processes of cellular overactivation and nonmalignant proliferation of tissue macrophages/histiocytes, which can cause multiorgan failure. Case report: We present a clinical case of 15-years old child, who was diagnosed with juvenile idiopathic arthritis in 2019. The disease started with macrophage activation syndrome. In the next years the child had multiple hospitalizations in the Pediatrics clinic, but in the course of the disease it developed the picture of severe necrotic pansinuitis with an orbital complication, which required an immediate surgical intervention. Ever since the child had an ongoing necrotizing process in the area of the nasal passages, sinuses, upper jaw and hard palate. Other complications were breakthrough of the hard palate, loss of healthy teeth from the upper dentition and creation of direct communication between the oral cavity and the left maxillary sinus. Conclusions: The diagnosis of MAS is difficult to make, but increased awareness of this disease is an essential for its recognition. The struggle with autoimmune diseases often lasts for years with periods of exacerbation and remission of symptoms. Complications related to them can affect different organs and systems and require interdisciplinary approach.

Clinical Spectrum and Therapeutic Management of Systemic Lupus Erythematosus-Associated Macrophage Activation Syndrome

Macrophage activation syndrome can be primary with a genetic etiology, or secondary, associated with malignancies, infections or systemic diseases. Its a severe and potentially life-threatening complication of autoimmune diseases. The incidence of MAS among patients with systemic lupus erythematosus is not well known, as most of the previous studies were limited to a small number of case series or case reports. In recent years it has been suggested that macrophage activation syndrome in systemic lupus erythemaosus may be underrecognized because it can mimic the clinical features of the underlying disease or be confused with an infectious complication. The diagnosis of macrophage activation sydrome in adults is supported by hyperferritinemia (higher than 2000 ng/ml), and/or splenomegaly, pronounced cytopenias, hypofibrinogenemia, characteristic cytokine profile and hypertriglyceridemia. In the case of systemic lupus erythematosus flare, hyerferritinemia is the strongest indicator to differentiate them from MAS. So far, no validated and universally embraced diagnostic criteria for macrophage activation syndrome in adult secondary to systemic lupus erythematosus are available. It is important to know the parameters that can guide the clinician towards the diagnosis of macrophage activation syndrome in adult with systemic lupus. Early diagnosis and intensive therapy are essential in improving clinical outcomes. Hence, we decided to write this mini- review to focus on the demographic data, on the pathophysiological mechanisms, clinical and laboratory manifestations, treatments, and outcomes of patients with systemic lupus erythematosus associated macrophage activation syndrome.

Experience with macrophage activation syndrome associated with systemic lupus erythematosus: A single-center study from Pakistan

Objective: The objective of the study was to evaluate the clinical, laboratory manifestations, and associations of macrophage activation syndrome (MAS) in a cohort of Pakistani patients with systemic lupus erythematous and to compare it with a well-characterized cohort of active systemic lupus erythematosus (SLE) without MAS.Materials and Methods: Patients with a diagnosis of SLE admitted from January 2017 to July 2019 were retrospectively reviewed. MAS ascertained by either clinical criteria or bone marrow biopsy were studied. Demographics, clinical, and laboratory parameters of MAS patients were evaluated and compared with a cohort of non-MAS active SLE.Results: A total of 305 patients of SLE were evaluated, out of these 18 patients had a diagnosis of MAS, making a MAS prevalence of 5.9%. Mean age of the patients was 27.25 ± 10.16 years. Female comprised 13 (72%) of MAS group. Fever was the most common clinical presentation (100%), followed by splenomegaly (38.9%) and lymphadenopathy (33.3%). At least 5 (27.8%0 patients had MAS as their initial manifestation. Anemia (88.9%), thrombocytopenia (88.9%), leukopenia (72%), and pancytopenia (55.6%) were prominent laboratory parameters. Mean serum ferritin of 1584 ng/ml and mean triglyceride of 270 mg/dl were reported. On comparing with non-MAS cohort; younger age, fever, lymphadenopathy, splenomegaly, mucocutaneous features, any type of cytopenia, high aspartate aminotransferase (AST), low albumin, and lactate dehydrogenase, all showed significant association with MAS (P < 0.05).Conclusion: Fever and associated cytopenias coupled with raised AST are strong predictors of MAS in patients with SLE.

Anti-melanoma differentiation-associated gene 5 antibody-positive dermatomyositis complicated with macrophage activation syndrome.

Background:Anti-melanoma differentiation-associated gene 5 (anti-MDA5) antibody-positive dermatomyositis (DM) has low survival rate, whereas macrophage activation syndrome (MAS) is a severe and life-threatening syndrome associated with autoimmune diseases. Their coexistence is very rare. This study aimed to describe the prevalence, clinical characteristics, and outcomes of anti-MDA5 antibodies-positive DM patients complicated with MAS.Methods:In this retrospective study, we enrolled DM patients with anti-MDA5 antibodies, who were hospitalized between 2016 and 2020 and included patients diagnosed with MAS.Results:We identified four (2%) DM patients with anti-MDA5 antibodies. They were females with interstitial lung disease (ILD). The level of aspartate aminotransferase (AST), lactate dehydrogenase (LDH), and ferritin were significantly higher in the MAS group than those without MAS (p < 0.05). Patients with MAS were significantly more likely to develop a dysphagia (p = 0.012). Literature review revealed eight similar cases. Together with the present study, we identified 12 patients complicated with ILD. The median age of disease onset was 52 years with a male to female ratio of 1:6. The median duration between DM onset and MAS diagnosis was 3 months. The mortality of MAS in anti-MDA5 antibody-positive DM was 50%. Patients who died were older than those who survived (56.7 years versus 35.5 years; p = 0.015).Conclusions:MAS was rare in anti-MDA5 antibody-positive DM. The higher the level of AST, LDH, and ferritin, the greater the risk of MAS. They were associated with high mortality rates, particularly in older patients.

Macrophage activation syndrome in patients with adult-onset Still's disease under tocilizumab treatment: A single-center observational study.

Macrophage activation syndrome (MAS) developed under tocilizumab treatment poses a diagnostic challenge. This study aims to demonstrate the frequency and the clinical features of MAS developed in patients with adult-onset Still's disease (AOSD) receiving tocilizumab. The consecutive AOSD patients treated with tocilizumab in our institution from April 2008 to March 2020 were studied. The frequency of clinically diagnosed MAS during tocilizumab treatment, their conformity to the several criteria relevant for MAS, and laboratory characteristics compared to AOSD flare were investigated. Of the 20 AOSD patients treated with tocilizumab, six developed clinically diagnosed MAS, four immediately after starting tocilizumab and two after long-term treatment. Some of them had already met the MAS criteria before starting tocilizumab. At MAS diagnosis, although some did not meet the MAS criteria due to lack of fever and/or the lower ferritin levels, all consistently showed sharp increases in ferritin along with marked abnormal changes in two or more different markers of organ damage, unlike the AOSD flares. MAS is not a rare complication in AOSD patients receiving tocilizumab. The clinical similarities between systemic AOSD and MAS, and substantial alterations in MAS features by inhibition of interleukin-6 signaling may limit the utility of the existing diagnostic/classification criteria in diagnosing MAS under tocilizumab treatment. The emergence of abnormalities in MAS-related organ damage markers with a rapid elevation of ferritin should be considered as MAS development in AOSD patients receiving tocilizumab even if the patients are afebrile or have relatively low ferritin levels.

Pediatric macrophage activation syndrome, recognizing the tip of the Iceberg.

Macrophage activation syndrome (MAS) is the name given to secondary hemophagocytic lymphohistiocytosis (sHLH) associated with rheumatic diseases. Previously, MAS has been best studied in children with systemic juvenile idiopathic arthritis (sJIA), who are at high risk of developing MAS. MAS/sHLH is a cytokine storm that results in multi-organ system failure and is frequently fatal. Early diagnosis and treatment is critical for improving survival. Various diagnostic tools have been developed for identifying MAS in the setting of sJIA, as well as for all forms of MAS/sHLH. These are largely based on clinical (e.g., fever) and laboratory features (e.g., cytopenias). None are perfectly sensitive and specific, however, increasing awareness of this condition is also paramount in making the diagnosis. Rare familial forms of HLH can also be diagnosed based on homozygous mutation in genes largely involved in perforin-mediated cytolytic function of lymphocytes (natural killer cells and CD8 T cells). Intriguingly, heterozygous defects in these same genes are frequently identified in patients with sHLH and MAS. Decreased cytolytic function results in prolonged interaction of the lytic lymphocytes and their target antigen presenting cells, thus resulting in the pro-inflammatory cytokine storm believed responsible for the multi-organ failure. Novel cytokine-targeted therapies are currently being explored for a less toxic yet effective alternative to chemotherapeutic approaches to treating children with sHLH/MAS. As increased recognition and diagnosis of MAS is on the rise, an earlier and cytokine-targeted approach to therapy will likely save many lives of children with this disorder.

Macrophage activation syndrome, a rare complication of primary Sj\xf6gren\u2019s syndrome: a case report

BackgroundThe association of macrophage activation syndrome and primary Sjögren’s syndrome has been rarely reported in the literature. We report the first observation of this association in Africa, south of the Sahara, and we discuss the diagnosis and therapeutic challenge.Case presentationA 26-year-old Mauritanian and Berber woman was followed for primary Sjögren’s syndrome. After a voluntary cessation of her usual background treatment, she was admitted to our department for an outbreak of her illness. A clinical examination revealed anemic syndrome, peripheral polyarthritis, coughing rales at both pulmonary bases, and fever at 39.5 °C. On biologic examination, there was bicytopenia with anemia at 5.70 g/dl, lymphopenia at 796/mm3, a biological inflammatory syndrome with a sedimentation rate at 137 mm in the first hour, C-reactive protein at 97 mg/l, hyperferritinemia at 1778 mg/l (9 normal value), and hypergammaglobulinemia at 20.7 g/l of polyclonal appearance. The triglycerides were 1.95 g/l (1.4 normal value) and the lactate dehydrogenase level was 491 IU/l (1.5 normal value). Cytological examination of a medullary puncture revealed an image of hemophagocytosis. An infectious screening was negative. Thoracic computed tomography showed non-specific interstitial lung disease. A diagnosis of macrophage activation syndrome complicating primary Sjögren’s syndrome was selected with a probability of 97.2%, according to H-Score. The evolution was favorable under a treatment including etoposide (VP-16).ConclusionMacrophage activation syndrome is a rare entity, rarely reported during primary Sjögren’s syndrome. Its spontaneous evolution is invariably fatal. There is no consensus on therapeutic treatment. Etoposide is a therapeutic option especially in forms refractory to corticosteroid therapy.

Clinical and laboratory features, treatment, and outcomes of macrophage activation syndrome in 80 children: a multi-center study in China.

Macrophage activation syndrome (MAS) is a major cause of morbidity and mortality in pediatric rheumatology. We aimed to further understand the clinical features, treatment, and outcome of MAS in China. A multi-center cohort study was performed in seven hospitals in China from 2012 to 2018. Eighty patients with MAS were enrolled, including 53 cases with systemic juvenile idiopathic arthritis (SJIA-MAS), 10 cases of Kawasaki disease (KD-MAS), and 17 cases of connective tissue disease (CTD-MAS). The clinical and laboratory data were collected before (pre-), at onset, and during full-blown stages of MAS. We compared the data among the SJIA-MAS, KD-MAS, and CTD-MAS subjects. 51.2% of patients developed MAS when the underlying disease was first diagnosed. In patients with SJIA, 22.6% (12/53) were found to have hypotension before the onset of SJIA-MAS. These patients were also found to have significantly increased aspartate aminotransferase (AST) and lactate dehydrogenase (LDH), as well as decreased albumin (P < 0.05), but no difference in alanine aminotransferase, ferritin, and ratio of ferritin/erythrocyte sedimentation rate (ESR) at onset of MAS when compared to pre-MAS stages of the disease. In addition, ferritin and ratio of ferritin/ESR were significantly elevated in patients at full-blown stages of SJIA-MAS compared to pre-MAS stage. Significantly increased ferritin and ratio of ferritin/ESR were also observed in patients with SJIA compared to in KD and CTD. Receiver-operating characteristic analysis showed that 12,217.5μg/L of ferritin and 267.5 of ferritin/ESR ratio had sensitivity (80.0% and 90.5%) and specificity (88.2% and 86.7%), respectively, for predicting full-blown SJIA-MAS. The majority of the patients received corticosteroids (79/80), while biologic agents were used in 12.5% (10/80) of cases. Tocilizumab was the most commonly selected biologic agent. The overall mortality rate was 7.5%. About half of MAS occurred when the underlying autoimmune diseases (SJIA, KD, and CTD) were first diagnosed. Hypotension could be an important manifestation before MAS diagnosis. Decreased albumin and increased AST, LDH, ferritin, and ratio of ferritin/ESR could predict the onset or full blown of MAS in patient with SJIA.

Development and initial validation of the MS score for diagnosis of macrophage activation syndrome in systemic juvenile idiopathic arthritis

ObjectiveTo develop and validate a diagnostic score that aids in identifying macrophage activation syndrome (MAS) in patients with systemic juvenile idiopathic arthritis (sJIA).MethodsThe clinical and laboratory features of 362 patients...

Comparison of serum biomarkers for the diagnosis of macrophage activation syndrome complicating systemic juvenile idiopathic arthritis

Our study aimed to compare the accuracy of serum biomarkers for the diagnosis of macrophage activation syndrome (MAS) complicating systemic juvenile idiopathic arthritis (s-JIA). Serum cytokine levels (neopterin, IL-18, and CXCL9 and soluble tumor necrosis factor receptor type I (sTNFR-I) and II) were determined by enzyme-linked immunosorbent assay in 78 patients with s-JIA, including 21 with MAS. Receiver operating characteristic curve analysis revealed area under the curve values and cut off values of neopterin, IL-18, CXCL9, sTNFR-II/I ratio and ferritin were 0.9465/19.5 nmol/l, 0.8895/69250 ng/ml, 0.9333/3130 pg/ml, 0.9395/3.796 and 0.8671/2560 ng/ml, respectively. Serum neopterin levels were significantly elevated in patients with MAS and those were correlated positively with disease activity. In conclusion, serum neopterin levels may be used as a promising indicator of disease activity in s-JIA and MAS and for evaluating it. It may also be a useful marker to diagnose the transition to MAS from active-phase s-JIA.

Cytokine profile of macrophage activation syndrome associated with Kawasaki disease

The present study aimed to assess the kinetics of cytokine release and compare the accuracy of serum biomarkers for the diagnosis of macrophage activation syndrome (MAS) associated with Kawasaki disease (KD). Serum neopterin, interleukin (IL)-18, IL-6 and soluble tumour necrosis factor receptor type I (sTNFR-I) and sTNFR-II levels were determined using enzyme-linked immunosorbent assay in 78 patients with KD, including five with MAS. Results were compared to the clinical features of MAS. Serum neopterin, IL-18, sTNFR-II levels and sTNFR-II/I ratio were significantly elevated in KD patients with MAS compared to those in the acute phase. Receiver operating characteristic curve analysis revealed areas under the curve and cutoff values of neopterin, IL-18, sTNFR-II levels and sTNFR-II/I ratio were 0.9750/30.0 nmol/L, 0.9813/1165 ng/mL, 0.9969/16,600 pg/mL and 0.9875/4.475, respectively. Serum sTNFR-II levels correlated positively with disease activity. These findings indicate that overproduction of interferon (IFN)–γ and TNF-α reflected by increased serum levels of neopterin and sTNFR-II are closely associated with the pathogenesis of MAS associated with KD. Serum sTNFR-II levels might be a useful marker to diagnose the transition to MAS.

Therapeutic Plasma Exchange as a rescue therapy in three patients of severe Dengue with Hyperferritinemia and acute hepatic failure : A Case Series

Severe Dengue Infection unresponsive to standard therapy carries a very high mortality with limited therapeutic options. Ferritin levels have been evaluated recently for its role as a diagnostic tool in dengue fever. It has also been shown to correlate with severity of dengue. Hyperferritinemia is an important marker for diagnosis of macrophage activation syndrome which is commonly seen in severe dengue. Immunomodulation has been attempted using steroids and IVIG therapy. Both are not recommended therapy for dengue patients of any severity. Treatment guidelines have been developed by World Health Organization(WHO) but there are variations between these guidelines. There are no robust trials and studies about use of plasmapheresis in Severe Dengue. High Volume Plasma Exchange(HVP) in acute hepatic failure have been well studied in recent randomized controlled trial by Larsen et al with improvement in outcome by increasing liver transplant-free survival further suggesting that the effect is mediated by dampening of innate immune response with Therapeutic plasma exchange(TPE). TPE has been attempted in patients of dengue with Hyperferritinemia associated multiorgan failure with variable success.WHO SEARO (World Health Organization in South-East Asia) guidelines recommends considering plasma exchange as a therapeutic option for management of severe dengue patients with hepatic encephalopathy who are clinically deteriorating with standard treatment. Based on the data by Larsen and WHO SEARO guidelines we instituted Plasmapheresis in severe dengue patients who were clinically unresponsive to standard therapies and were deteriorating.

The rheumatology/hematology interface: CAPS and MAS diagnosis and management.

Catastrophic antiphospholipid antibody syndrome (CAPS) and macrophage activation syndrome (MAS) are both life-threatening hematologic disorders that infrequently afflict patients with rheumatologic disease. CAPS is characterized by fulminant multiorgan damage related to small vessel thrombosis in the setting of persistent antiphospholipid antibodies. It can occur in patients with rheumatologic diseases such as systemic lupus erythematosus but can also affect patients who do not have rheumatologic disease. By contrast, the term MAS is applied when patients with rheumatologic disease develop hemophagocytic lymphohistiocytosis (HLH); therefore, patients with MAS have an underlying rheumatologic disease by definition. Similar to CAPS, HLH/MAS can have a fulminant presentation, but the pathogenesis and manifestations are different. In both CAPS and MAS, management generally includes but is not limited to immunosuppression with steroids. Fatalities are relatively common and morbidity is often significant. Early recognition of these disorders and initiation of timely treatment are important. More effective therapies for both syndromes are urgently needed.