New Recommendations for the Diagnosis and Treatment of MAS, HLH, Interferonopathies

We still don’t fully understand a number of rare diseases. A lack of awareness, lack of interest, and lack of funding all play a role, and medical professionals simply can’t figure some conditions out yet. When this happens, it’s difficult to create a standard of care and establish recommendations for diagnosis and treatment. Luckily, this just changed for a number of rare, autoinflammatory diseases. Recommendations for the treatment of macrophage activation syndrome (MAS), hemophagocytic lymphohistiocytosis (HLH), and Type 1 and interleukin (IL)-1-mediated interferonopathies were recently released at the European Congress of Rheumatology.

Recommendations for Autoinflammatory Diseases

The recommendations were created by the American College of Rheumatology (ACR) and the European Alliance of Associations for Rheumatology (EULAR). In fact, this is the first guidance given by EULAR in regard to these autoinflammatory conditions. They come to address the need to standardize care for rare conditions, which becomes possible as we gain a deeper understanding of them.

In order to provide the best outcomes for patients, there must be a standard for diagnosis and treatment. Doctors must know how to recognize and manage HLH, MAS, and interferonopathies if they want to successfully treat their patients. Now that research has provided clarity on the inner workings of autoinflammatory diseases, they can begin to construct this standard of care.

Two presenters noted that recent research has linked these conditions to “the pathologic production of major proinflammatory cytokines.” Armed with this information, doctors utilized anticytokine treatments. These have proven to be very successful treatments, changing the lives of patients.

To craft their recommendations, EULAR and ACR divided each disease into three working groups. They then created clinical questions before conducting systematic literature reviews of materials published between 1970 and 2020 on PubMed, EMBASE, and Cochrane Library. Materials were excluded if they were non-English studies, basic science studies, case studies, or utilized animal models. After finishing the reviews, they regrouped to create their final recommendations.

IL-1-Mediated Conditions

The guidelines for IL-1-mediated conditions focused specifically on tumor necrosis factor receptor-associated periodic syndrome (TRAPS), deficiency of the IL-1 receptor antagonist (DIRA), cryopyrinopathies (CAPS), and mevalonate kinase deficiency (MKD). In terms of symptoms, these conditions present with intermittent flares or chronic inflammation. This raises the risk of mortality, as it can cause organ damage and morbidity.

In terms of diagnosis, a team of specialists across multiple disciplines will be necessary. Not only should they provide an accurate diagnosis, but they should keep any possible longer-term care or complications in mind as well. In addition, genetic testing should become standard, alongside a clinical workup.

Turning to treatment, goals include managing symptoms and returning inflammatory biomarkers to normal levels. For long-term care, doctors should focus on helping the patient self-manage and learn to make their own medical decisions as children are typically impacted by these conditions. Other goals should include a smooth transition from child to adult care and treatment that adjusts to changing needs.

Type 1 Interferonopathies

Like the recommendations for IL-1-mediated conditions, these guidelines focused on specific types of type 1 interferonopathies:

These conditions all share one thing in common: they trigger chronic, organ-specific inflammation. Without the proper management, patients can experience progressive organ damage, morbidity, and a higher risk of mortality.

EULAR and ACR’s recommendations state that genetic testing should be used to confirm a diagnosis for these conditions. This way, doctors can target their treatments, look for possible complications, discern a prognosis, and provide genetic counseling. Moving onto treatment, therapy should aim to fight inflammation in order to protect the organs from damage while improving quality of life. This will require a multidisciplinary team.


The two organizations recognize that early diagnosis and treatment for HLH and MAS is often difficult. Symptoms and lab findings are non-specific, making a definitive diagnosis challenging. To fight this problem, the recommendations state that rapid diagnostic evaluation should begin even if not all of the diagnostic criteria are met. They point out that systemic hyperinflammation holds the potential to progress to HLH or MAS, so if it is present, doctors should immediately begin the diagnostic and treatment process.

Early, urgent intervention is best for the treatment of these conditions. After evaluating the extent of inflammation and organ dysfunction, therapy should aim to preserve the diagnostic workup’s integrity and limit immunopathology while limiting any therapy-related toxicities.

Looking Forward

It is extremely important to produce a standard of care for all conditions. Doctors are able to reference these standards to best treat their patients. Now that HLH, MAS, IL-1-mediated conditions, and type 1 interferonopathies all have recommendations, patients will hopefully experience an improved quality of life.

Find the source article here.

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