In a letter to the editor of the journal Nefrologia, a recent case report focused on a single patient with a diagnosis of simultaneous systemic lupus erythematosus (SLE) and Gaucher disease (GD), two unrelated medical conditions.
The study, “Gaucher disease and Lupus: A rare association?” aims to present and characterize a possible association between the two diseases.
Unlike SLE, which acts rather systemically and is the end product of a combination of genetic and environmental factors, Gaucher disease is an inherited genetic disorder that is characterized by an accumulation of specific lipids – due to an enzyme’s inability to break them down – in specific organs, such as the spleen and the liver, causing those organs to become enlarged.
But just like SLE, Gaucher disease can manifest clinically in different ways, some of which can be observed in body regions such as the bone marrow. Literature indicates that Gaucher disease patients may have increased susceptibility to other conditions, including certain cancers and diseases, such as Parkinson’s disease.
The exact relationship between Gaucher disease and lupus has not been investigated, a knowledge gap which, if filled, can have critical ramifications for the diagnosis and treatment of patients with autoimmune diseases in general, and not just those with the two conditions.
In the letter, researchers report the case of a 32-year-old woman with Gaucher disease who also had a grandmother with GD, an uncle with SLE and a cousin with rheumatoid arthritis.
When she was 30 years old, the woman began noticing a host of symptoms associated with sun exposure, like malar-rash and chest eczema, and soon after she experienced a loss of appetite, nausea, oral ulcers, and a significantly elevated blood pressure.
A blood analysis revealed proteinuria (an abnormal amount of proteins in urine) and elevated creatinine, two warning signs of SLE. The patient also had a positive ANA assay (a test for lupus), and follow-up tests revealed liver enlargement, a thickening in the heart membranes, bone alterations, and joint effusion.
The woman was then officially diagnosed with lupus nephritis, and started adequate treatment for the condition. However, she appeared to be intolerant to hydroxycloroquine, the chosen drug treatment. Six months after the patient’s discharge, her clinical phenotype was significantly improved.
Researchers suggest that the link between Gaucher disease and SLE, and their “immunologic proximity,” could be lipid accumulation – and all metabolic dysregulations that accompany it – triggering a chronic stimulation of the immune system. This means that the varied GD manifestations are the driving forces fueling a lupus flare.
“Increasing clinical evidence suggests that the pathophysiology of classic GD is more complex and involves system-wide dysfunction of cell types other than macrophages. Therefore, the immunological disturbances that occur in GD may function as a trigger to the development of SLE, bringing up the already existing doubt that the defects in lipid metabolism could contribute to the development of autoimmunity,” the team wrote in their report.
The poor diagnostic criteria for SLE, in combination with the rich symptomatology of both SLE and GD, makes the diagnosis difficult, noted the research team, concluding that “the relationship between GD and SLE is not yet established. The involvement of immune cells has been implicated, but the underlying molecular defect is poorly understood. Further studies are necessary to highlight the possible immunologic proximity between these two rare conditions.”