Drug-induced aseptic meningitis

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Drug-Induced Aseptic Meningitis (DIAM) is a type of aseptic meningitis related to the use of medications such as nonsteroidal anti-inflammatory drugs (NSAIDs) or biologic drugs such as intravenous immunoglobulin (IVIG). [1] Additionally, this condition generally shows clinical improvement after cessation of the medication, as well as a tendency to relapse with resumption of the medication. [2]

Contents

Signs and Symptoms


The signs and symptoms of DIAM are similar to infectious meningitis including but not limited to headache, fever, neck stiffness, altered mental status and other neurological deficits such as numbness, paresthesias, seizure or weakness. Notably, the patient will have had recent exposure to one of the causative medications. [2] [3]

Causes

The following is a list of medications associated with DIAM.

Pathophysiology

Meningitis, whether acute or chronic, is by definition an inflammation of the meninges. This can be due to both infectious or non-infectious reasons. DIAM is a noninfectious meningitis that is associated with the use of certain medications listed above. The pathogenesis of DIAM is poorly understood and may be related to autoimmune hypersensitivity reactions, although it may vary depending on the inciting medication. For instance, DIAM caused by OKT3 antibodies may be mediated by cytokine release rather than hypersensitivity reactions. [3] There is an association with certain underlying conditions such as Systemic Lupus Erythematosus (SLE), and other underlying conditions that were present in a small amount of patients included Sjögren syndrome, Idiopathic thrombocytopenic purpura, rheumatoid arthritis, HIV, Crohn's disease. [3]

Diagnosis

Historically, the process of diagnosis involved attempting to identify any infectious causes as these may be treatable with antibiotics or other medications. Lumbar puncture would be performed to collect cerebral spinal fluid (CSF) to culture for bacterial growth. Growth indicated a bacterial meningitis, while no growth indicated another cause denoted "aseptic" meningitis. [1] The most common form of this is viral meningitis. [1] Recent medical advances allows rapid polymerase chain reaction (PCR) testing that analyzes the CSF for DNA or RNA. This can quickly determine if there are bacterial or viral species present in the CSF. If these are ruled out, as well as other causes such as parasitic or fungal causes, then the cause of the meningitis is likely noninfectious in nature. [2] DIAM is among these noninfectious causes of aseptic meningitis.[ citation needed ]

Once infectious causes ruled out, noninfectious causes should be investigated. These include a history of chemical irritation from recent surgery or chemicals injected into the subarachnoid space such as spinal anesthesia, other inflammatory or vascular conditions such as sarcoidosis or vasculitis, as well as Neoplastic conditions such as lymphoma. [1]

CSF analysis tends to show inflammatory changes in DIAM such as elevated white blood cells and elevated protein levels. Glucose was either normal or low. [3] MRI and CT imaging of the brain has shown changes consistent with Blood-brain barrier disruption or cerebral edema including T2-weighted changes that were normalized after resolution of the condition. [3]

In patients with SLE, DIAM should be distinguished from lupus aseptic meningitis (LAM). This can be done by CSF analysis (DIAM has a neutrophilic predominance while LAM has a lymphocytic predominance), as well as assessment of relevant labs such as complement levels and signs of Lupus flareup. [3]

Treatment

Immediate cessation of offending medications. [3]

Prognosis

Generally, excellent prognosis with complete recovery if the offending medication is ceased. [3]

Epidemiology

The occurrence of aseptic meningitis in general is approximately 20 per 100,000, but the most common cause of aseptic meningitis is viral. [1]

Related Research Articles

<span class="mw-page-title-main">Nonsteroidal anti-inflammatory drug</span> Class of therapeutic drug for relieving pain and inflammation

Non-steroidal anti-inflammatory drugs (NSAID) are members of a therapeutic drug class which reduces pain, decreases inflammation, decreases fever, and prevents blood clots. Side effects depend on the specific drug, its dose and duration of use, but largely include an increased risk of gastrointestinal ulcers and bleeds, heart attack, and kidney disease.

<span class="mw-page-title-main">Encephalitis</span> Inflammation of the brain

Encephalitis is inflammation of the brain. The severity can be variable with symptoms including reduction or alteration in consciousness, headache, fever, confusion, a stiff neck, and vomiting. Complications may include seizures, hallucinations, trouble speaking, memory problems, and problems with hearing.

<span class="mw-page-title-main">Viral meningitis</span> Medical condition

Viral meningitis, also known as aseptic meningitis, is a type of meningitis due to a viral infection. It results in inflammation of the meninges. Symptoms commonly include headache, fever, sensitivity to light and neck stiffness.

<span class="mw-page-title-main">Hypersensitivity</span> Medical condition

Hypersensitivity refers to undesirable reactions produced by the normal immune system, including allergies and autoimmunity. They are usually referred to as an over-reaction of the immune system and these reactions may be damaging and uncomfortable. This is an immunologic term and is not to be confused with the psychiatric term of being hypersensitive which implies to an individual who may be overly sensitive to physical and/or emotional stimuli. Although there is a relation between the two – studies have shown that those individuals that have ADHD are more likely to have hypersensitivity reactions such as allergies, asthma, eczema than those who do not have ADHD. Hypersensitivity reactions can be classified into four types.

<span class="mw-page-title-main">Kikuchi disease</span> Medical condition

Kikuchi disease was described in 1972 in Japan. It is also known as histiocytic necrotizing lymphadenitis, Kikuchi necrotizing lymphadenitis, phagocytic necrotizing lymphadenitis, subacute necrotizing lymphadenitis, and necrotizing lymphadenitis. Kikuchi disease occurs sporadically in people with no family history of the condition.

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<span class="mw-page-title-main">Aseptic meningitis</span> Medical condition

Aseptic meningitis is the inflammation of the meninges, a membrane covering the brain and spinal cord, in patients whose cerebral spinal fluid test result is negative with routine bacterial cultures. Aseptic meningitis is caused by viruses, mycobacteria, spirochetes, fungi, medications, and cancer malignancies. The testing for both meningitis and aseptic meningitis is mostly the same. A cerebrospinal fluid sample is taken by lumbar puncture and is tested for leukocyte levels to determine if there is an infection and goes on to further testing to see what the actual cause is. The symptoms are the same for both meningitis and aseptic meningitis but the severity of the symptoms and the treatment can depend on the certain cause.

Warm antibody autoimmune hemolytic anemia (WAIHA) is the most common form of autoimmune haemolytic anemia. About half of the cases are of unknown cause, with the other half attributable to a predisposing condition or medications being taken. Contrary to cold autoimmune hemolytic anemia which happens in cold temperature (28–31 °C), WAIHA happens at body temperature.

Common variable immunodeficiency (CVID) is an immune disorder characterized by recurrent infections and low antibody levels, specifically in immunoglobulin (Ig) types IgG, IgM and IgA. Symptoms generally include high susceptibility to foreign invaders, chronic lung disease, and inflammation and infection of the gastrointestinal tract. CVID affects males and females equally. The condition can be found in children or teens but is generally not diagnosed or recognized until adulthood. The average age of diagnosis is between 20 and 50. However, symptoms vary greatly between people. "Variable" refers to the heterogeneous clinical manifestations of this disorder, which include recurrent bacterial infections, increased risk for autoimmune disease and lymphoma, as well as gastrointestinal disease. CVID is a lifelong disease.

<span class="mw-page-title-main">Myositis</span> Medical condition

Myositis is a rare disease that involves inflammation of the muscles. This can present with a variety of symptoms such as skin involvement, muscle weakness, and other organ involvement. Systemic symptoms such as weight loss, fatigue, and low fever can also present.

Granulomatous meningoencephalitis (GME) is an inflammatory disease of the central nervous system (CNS) of dogs and, rarely, cats. It is a form of meningoencephalitis. GME is likely second only to encephalitis caused by canine distemper virus as the most common cause of inflammatory disease of the canine CNS. The disease is more common in female dogs of young and middle age. It has a rapid onset. The lesions of GME exist mainly in the white matter of the cerebrum, brainstem, cerebellum, and spinal cord. The cause is only known to be noninfectious and is considered at this time to be idiopathic. Because lesions resemble those seen in allergic meningoencephalitis, GME is thought to have an immune-mediated cause, but it is also thought that the disease may be based on an abnormal response to an infectious agent. One study searched for viral DNA from canine herpesvirus, canine adenovirus, and canine parvovirus in brain tissue from dogs with GME, necrotizing meningoencephalitis, and necrotizing leukoencephalitis, but failed to find any.

<span class="mw-page-title-main">Drug-induced lupus erythematosus</span> Medical condition

Drug-induced lupus erythematosus is an autoimmune disorder caused by chronic use of certain drugs. These drugs cause an autoimmune response producing symptoms similar to those of systemic lupus erythematosus (SLE). There are 38 known medications to cause DIL but there are three that report the highest number of cases: hydralazine, procainamide, and quinidine. While the criteria for diagnosing DIL has not been thoroughly established, symptoms of DIL typically present as muscle pain and joint pain. Generally, the symptoms recede after discontinuing use of the drugs.

<span class="mw-page-title-main">Deracoxib</span> Chemical compound

Deracoxib is a nonsteroidal anti-inflammatory drug (NSAID) of the coxib class, used in dogs to treat pain associated with osteoarthritis, or to prevent pain following orthopedic or dental surgery. It is available as beef-flavored tablets.

Cerebritis is the inflammation of the cerebrum, which performs a number of important functions, such as memory and speech. It is also defined as a purulent nonencapsulated parenchymal infection of brain which is characterized by nonspecific features on CT scans and cannot reliably be distinguished from neoplasms.

<span class="mw-page-title-main">Lupus erythematosus</span> Human disease

Lupus erythematosus is a collection of autoimmune diseases in which the human immune system becomes hyperactive and attacks healthy tissues. Symptoms of these diseases can affect many different body systems, including joints, skin, kidneys, blood cells, heart, and lungs. The most common and most severe form is systemic lupus erythematosus.

The Central Nervous System controls most of the functions of the body and mind. It comprises the brain, spinal cord and the nerve fibers that branch off to all parts of the body. The Central Nervous System viral diseases are caused by viruses that attack the CNS. Existing and emerging viral CNS infections are major sources of human morbidity and mortality. Virus infections usually begin in the peripheral tissues, and can invade the mammalian system by spreading into the peripheral nervous system and more rarely the CNS. CNS is protected by effective immune responses and multi-layer barriers, but some viruses enter with high-efficiency through the bloodstream and some by directly infecting the nerves that innervate the tissues. Most viruses that enter can be opportunistic and accidental pathogens, but some like herpes viruses and rabies virus have evolved in time to enter the nervous system efficiently, by exploiting the neuronal cell biology. While acute viral diseases come on quickly, chronic viral conditions have long incubation periods inside the body. Their symptoms develop slowly and follow a progressive, fatal course.

<span class="mw-page-title-main">Lupus</span> Human autoimmune disease

Lupus, technically known as systemic lupus erythematosus (SLE), is an autoimmune disease in which the body's immune system mistakenly attacks healthy tissue in many parts of the body. Symptoms vary among people and may be mild to severe. Common symptoms include painful and swollen joints, fever, chest pain, hair loss, mouth ulcers, swollen lymph nodes, feeling tired, and a red rash which is most commonly on the face. Often there are periods of illness, called flares, and periods of remission during which there are few symptoms.

<span class="mw-page-title-main">Meningitis</span> Inflammation of the membranes around the brain and spinal cord

Meningitis is acute or chronic inflammation of the protective membranes covering the brain and spinal cord, collectively called the meninges. The most common symptoms are fever, headache, and neck stiffness. Other symptoms include confusion or altered consciousness, nausea, vomiting, and an inability to tolerate light or loud noises. Young children often exhibit only nonspecific symptoms, such as irritability, drowsiness, or poor feeding. A non-blanching rash may also be present.

Drug-induced autoimmune hemolytic anemia is a form of hemolytic anemia.

Immunoglobulin therapy is the use of a mixture of antibodies to treat several health conditions. These conditions include primary immunodeficiency, immune thrombocytopenic purpura, chronic inflammatory demyelinating polyneuropathy, Kawasaki disease, certain cases of HIV/AIDS and measles, Guillain-Barré syndrome, and certain other infections when a more specific immunoglobulin is not available. Depending on the formulation it can be given by injection into muscle, a vein, or under the skin. The effects last a few weeks.

References

  1. 1 2 3 4 5 6 7 Ropper, Allan H. (22 May 2019). Adams and Victor's principles of neurology. Samuels, Martin A., Klein, Joshua. (Eleventh ed.). New York. ISBN   978-0-07-184262-4. OCLC   1083701139.
  2. 1 2 3 4 5 6 Koroshetz, Walter (2018). Harrison's principles of internal medicine. New York, NY: McGraw-Hill. pp. Chapter 134. ISBN   978-1259644030.
  3. 1 2 3 4 5 6 7 8 9 10 Garcia-Monco, JC (June 14, 1999). "The challenge of drug-induced aseptic meningitis". JAMA Internal Medicine. 159 (11): 1185–1194. doi: 10.1001/archinte.159.11.1185 . PMID   10371226.
  4. 1 2 Morís, German; Garcia-Monco, Juan Carlos (September 2014). "The challenge of drug-induced aseptic meningitis revisited". JAMA Internal Medicine. 174 (9): 1511–1512. doi: 10.1001/jamainternmed.2014.2918 . ISSN   2168-6114. PMID   25003798.
  5. ↑ Durand JM, Suchet L, Morange S, Michel B (1996). "Ranitidine and aseptic meningitis". BMJ. 312 (7035): 886. doi:10.1136/bmj.312.7035.886a. PMC   2350562 . PMID   8611881.
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