Glucocorticoid therapy falls short in rare cases of IgG4-RD, per report
Man, 67, with clots in brain blood vessels failed to respond to standard treatment
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Glucocorticoid therapy alone is often not enough to manage rare cases of IgG4-related disease (IgG4-RD) that manifest with thickening of the membrane around the brain and recurrent blood clots blocking the brain’s blood vessels, according to a team of researchers in China who detailed the treatment of an older man with IgG4-RD with this presentation, for whom the standard strategy was ineffective.
The man was initially given glucocorticoids — IgG4-RD’s first-line treatment — which provided temporary relief. However, using just those immunosuppressive medications failed to adequately manage his disease over the long term, the researchers noted.
Ultimately, per the team, this patient was successfully treated with a combination of rituximab and blood-thinning medications, used to help reduce blood clots.
This case, along with others in the literature, suggests that glucocorticoids alone are often not sufficient to manage this rare manifestation of IgG4-RD, the team reported.
The study, “Recurrent cerebral venous thrombosis associated with IgG4-related hypertrophic pachymeningitis: Case report and literature review,” was published in the journal BMC Neurology.
An inflammatory disease, IgG4-RD is marked by abnormal clumps of immune cells, particularly B-cells producing a type of antibody called IgG4. These atypical immune clumps can cause inflammation and scarring in many different parts of the body, leading to a wide range of symptoms and clinical profiles.
First-line treatment for IgG4-RD usually involves glucocorticoids, which are powerful anti-inflammatory medications that also suppress the immunosuppressive system. If glucocorticoids aren’t sufficient to control the disease, other immunosuppressive medicines may be used.
Rituximab, marketed as Rituxan in the U.S. and Mabthera in Europe (with biosimilars available), is an antibody-based therapy that works by killing B-cells. While it is not approved for IgG4-RD, it is often used off-label for this indication.
Rare case marked by ‘complex interplay’ of underlying issues
In some cases, IgG4-RD can affect the central nervous system, comprising the brain and spinal cord, and lead to hypertrophic pachymeningitis (HP). This condition is marked by abnormal thickening of the membrane that surrounds the brain. IgG4-RD that results in HP is abbreviated as IgG4-RHP.
In a limited but growing number of published cases, IgG4-RHP has been associated with cerebral venous thrombosis (CVT), or the blockage of brain blood vessels due to blood clots.
“This suggests a complex interplay between chronic inflammation, [scarring], and [blood vessel] obstruction, warranting further investigation into the underlying mechanisms,” the researchers wrote.
Now, a team from Peking University International Hospital in Beijing described the case of a 67-year-old man who sought medical attention for persistent headaches that had occurred for about a year. In the months before he sought care, he started to also experience nausea, vomiting, and hearing loss in his left ear.
A battery of diagnostic tests was performed. Blood tests showed high levels of IgG4 and an elevated erythrocyte sedimentation rate, a marker of inflammation. A biopsy of the membrane that surrounds the brain revealed abnormal clumps of IgG4-producing B-cells, consistent with IgG4-RHP. At the same time, a brain MRI scan showed evidence of CVT.
The man was given high-dose, intravenous, or into-the-vein, glucocorticoids, which rapidly relieved his headaches and resulted in a partial reopening of the affected blood vessels, according to the researchers.
However, as soon as he started tapering off these medications, his symptoms recurred, and the blood vessels were again found to be blocked. He restarted high-dose glucocorticoids, which again resulted in pronounced clinical benefits.
Still, switching to a lower oral dose of glucocorticoids, even in combination with the immunosuppressive treatment cyclophosphamide, was found to be insufficient to effectively control the man’s condition. He also started to experience glucocorticoid-related side effects, including weight gain and bone damage.
After consulting with a specialist in inflammatory and autoimmune diseases, the man was started on treatment with rituximab. This markedly eased his headaches, though brain imaging revealed the blood vessels were still blocked. He was therefore also given blood thinners, which effectively reopened the blood vessels.
Glucocorticoid therapy works, but not enough for maintenance
The case prompted the researchers to conduct a literature review, which revealed eight previously reported cases of IgG4-RHP associated with CVT. Data from those cases and the current case showed that patients’ ages ranged from 26 to 67, with a roughly even distribution of men and women.
“This reflects that IgG4-RHP with CVT can occur across a wide demographic,” the researchers wrote. The team noted that disease duration among the patients also varied “significantly, from acute presentations to chronic cases extending over several years.”
the cases reviewed here suggest that, while [glucocorticoids] are effective in the initial management, additional immunosuppressive agents like rituximab may be necessary for long-term stabilization.
Importantly, the researchers found that, in many of these cases, glucocorticoid therapy alone was not sufficient to manage the disease. Rituximab resulted in clinical benefits in cases with recurrent disease or that were resistant to glucocorticoids, the team noted.
“IgG4-RHP with CVT represents a rare but challenging clinical entity,” the scientists concluded, noting that “the cases reviewed here suggest that, while [glucocorticoids] are effective in the initial management, additional immunosuppressive agents like rituximab may be necessary for long-term stabilization.”
Still, because there are only a few published cases of this rare manifestation of IgG4-RD, the scientists highlighted a need for more research on how best to manage patients with IgG4-RHP that causes CVT.
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