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The cornerstone of therapy is reduction in immunosuppression. A recent surge in BKVAN correlates with use of potent immunosuppressant drugs, such as tacrolimus and mycophenolate mofetil (MMF). Studies have not shown any correlation between BKVAN and a single immunosuppressive agent but rather the overall immunosuppressive load.
- No guidelines or drug levels and doses exist for proper reduction of immunosuppressants in BKVAN
- Most common methods:
1. Withdrawal of MMF or tacrolimus
2. Replacement of tacrolimus by cyclosporine
3. Overall reduction of immunosuppressive load
4. Some cyclosporine trough levels reported to be reduced to 100–150 ng/ml and tacrolimus levels reduced to 3–5 ng/ml
- Retrospective analysis of 67 patients concluded graft survival was similar between reduction and discontinuation of agents.
- Single center study showed renal allografts were preserved in 8/8 individuals managed with reduction in immunosuppression while graft loss occurred in 8/12 patients treated with an increase in therapy for what was thought to be organ rejection.
Other therapeutic options include Leflunomide, Cidofovir, IVIG, and the fluoroquinolones. Leflunomide, a pyrimidine synthesis inhibitor is now generally accepted as the second treatment option behind reduction of immunosuppression.
The rationale behind using leflunomide in BKVAN comes from its combined immunosuppressive and antiviral properties. Two studies consisting of 26 and 17 patients who developed BKVAN on a three-drug regimen of tacrolimus, MMF, and steroids had their MMF replaced with leflunomide 20–60 mg daily. 84 and 88% of patients, respectively had clearance or a progressive reduction in viral load and a stabilization or improvement of graft function (7). In a study conducted by Teschner et al. in 2009, 12/13 patients who had their MMF exchanged with leflunomide cleared the virus by 109 days. In a case series, there was improvement or stabilization in 23/26 patients with BKVAN after switching MMF to leflunomide.
There are no dosing guidelines for leflunomide in BKVAN. Patient to patient variability has made dosing and monitoring of leflunomide extremely difficult.
- Study of 26 and 17 patients were dosed between 20 mg/day and 60 mg/day with trough levels of 50—100 µg/ml. Failure was seen in patients with leflunomide plasma levels < 40 µg/ml.
- One study of 21 patients found that low levels ( 40 µg/ml) had similar effects on the rate of viral clearance. Those with higher levels had more adverse events (hematologic, hepatic).
- In the study by Teschner et al., dosages and drug concentration showed no correlation with substantial variation from person to person.
- In the Teschner study, low drug concentrations were associated with decrease in viral load. This makes it difficult to determine whether or not reduction of viral load or addition of leflunomide was the cause for viral clearance.
Once a diagnosis of JDMS is made, the treatment is often a 3-day course of Intravenous ("pulse") steroids (methylprednisolone, Solu-Medrol), followed by a high dose of oral prednisone (usually 1–2 mg/kg of body weight) for several weeks. This action usually brings the disease under control, lowering most lab tests to or near normal values. Some minor improvement in muscle symptoms may also be seen in this time, but normally it takes a long time for full muscle strength to be regained.
Once the disease process is under control, oral steroids are tapered gradually to minimize their side effects. Often, steroid-sparing drugs, such as methotrexate (a chemotherapy drug) or other DMARDs, are given to compensate for the reduction in oral steroids. Once the oral steroids are reduced to a less toxic level, the sparing agents can also be gradually withdrawn. Lab results are closely monitored during the tapering process to ensure that the disease does not recur.
In the cases where steroids or second-line drugs are not tolerated or are ineffective, there are other treatments that can be tried. These include other chemotherapy drugs, such as ciclosporin, infliximab, or other DMARDs. Another is intravenous immunoglobulin (IVIg), a blood product that has been shown to be very effective against JDMS.
To treat the skin rash, anti-malarial drugs, such as hydroxychloroquine (Plaquenil) are usually given. Topical steroid creams (hydrocortisone) may help some patients, and anti-inflammatory creams (such as tacrolimus) are proving to be very effective. Dry skin caused by the rash can be combated by regular application of sunscreen or any moisturizing cream. Most JDM patients are very sensitive to sun exposure, and sunburn may be a disease activity trigger in some, so daily application of high-SPF sunscreen is often recommended.
The first line treatment for polymyositis is corticosteroids. Specialized exercise therapy may supplement treatment to enhance quality of life.
Treatment usually involves high doses of steroids such as dexamethasone. While high doses of steroids may risk laminitis, low doses are associated with refractory cases. Antibiotics are used to treat any residual nidus of "S. equi". Non-steroidal anti-inflammatory drugs (NSAIDs), such as phenylbutazone or flunixin, may be useful to reduce fever and relieve pain. Intravenous DMSO is sometimes used as a free-radical scavenger and anti-inflammatory. Additionally, wrapping the legs may reduce edema and skin sloughing. Supportive care with oral or IV fluids may also be required.
Antibiotics are commonly used to prevent secondary bacterial infection. There are no specific antiviral drugs in common use at this time for FVR, although one study has shown that ganciclovir, PMEDAP, and cidofovir hold promise for treatment. More recent research has indicated that systemic famciclovir is effective at treating this infection in cats without the side effects reported with other anti-viral agents. More severe cases may require supportive care such as intravenous fluid therapy, oxygen therapy, or even a feeding tube. Conjunctivitis and corneal ulcers are treated with topical antibiotics for secondary bacterial infection.
Lysine is commonly used as a treatment, however in a 2015 systematic review, where the authors investigated all clinical trials with cats as well as "in vitro" studies, concluded that lysine supplementation is not effective for the treatment or prevention of feline herpesvirus 1 infection.
In severe cases of PM and DM with systemic signs, an initial three to five days on intravenous corticosteroid (methylprednisolone) may be used; but normally treatment begins with a single daily (after breakfast) high dose of oral corticosteroid (prednisone). After a month or so the strength of every second day's dose is very gradually reduced over three to four months, to minimize the negative effects of the prednisone. When a high dose of prednisone cannot be reduced without losing muscle strength, or when prednisone is effective but it is producing significant complications, "steroid sparing" oral immunosuppressants such as azathioprine, mycophenolate mofetil, methotrexate and cyclosporine, may be used in combination with reduced prednisone. Some of these steroid sparing drugs can take several months to demonstrate an effect.
To minimize side effects, patients on corticosteroids should follow a strict high-protein, low-carbohydrate, low-salt diet; and with long-term corticosteroid use a daily calcium supplement and weekly vitamin D supplement (and a weekly dose of Fosamax for postmenopausal women) should be considered.
For patients not responding to this approach there is weak evidence supporting the use of intravenous immunoglobulin, ciclosporin, tacrolimus, mycophenolate mofetil and other agents; and trials of rituximab have indicated a potential therapeutic effect.
A wide variety of treatment modalities are currently recommended including Immunosuppressive agents, intravenous immunoglobulins (IVIG), and antiviral agents although the effectiveness of these treatments are not well established and no specific treatment is available.
Polymyositis and dermatomyositis are first treated with high doses of a corticosteroids
Ribavirin is one medication which has shown good potential for the treatment of HPIV-3 given recent in-vitro tests (in-vivo tests show mixed results). Ribavirin is a broadscale anti-viral and is currently being administered to those who are severely immuno-compromised, despite the lack of conclusive evidence for its use. Protein inhibitors and novel forms of medication have also been proposed to relieve the symptoms of infection.
Furthermore, antibiotics may be used if a secondary bacterial infection develops. Corticosteroid treatment and nebulizers are also a first line choice against croup if breathing difficulties ensue.
Treatments of proven efficacy are currently limited mostly to herpes viruses and human immunodeficiency virus. The herpes virus is of two types: herpes type 1 (HSV-1, or oral herpes) and herpes type 2 (HSV-2, or genital herpes). Although there is no particular cure; there are treatments that can relieve the symptoms. Drugs like Famvir, Zovirax, and Valtrex are among the drugs used, but these medications can only decrease pain and shorten the healing time. They can also decrease the total number of outbreaks in the surrounding. Warm baths also may relive the pain of genital herpes.
Human Immunodeficiency Virus Infection (HIV) is treated by using a combination of medications to fight against the HIV infection in the body. This is called antiretroviral therapy (ART). ART is not a cure, but it can control the virus so that a person can live a longer, healthier life and reduce the risk of transmitting HIV to others around him. ART involves taking a combination of HIV medicines (called an HIV regimen) every day, exactly as prescribed by the doctor. These HIV medicines prevent HIV Virus from multiplying (making copies of itself in the body), which reduces the amount of HIV in the body. Having less HIV in the body gives the immune system a chance to recover and fight off infections and cancers. Even though there is still some HIV in the body, the immune system is strong enough to fight off infections and cancers. By reducing the amount of HIV in the body, HIV medicines also reduce the risk of transmitting the virus to others. ART is recommended for all people with HIV, regardless of how long they’ve had the virus or how healthy they are. If left untreated, HIV will attack the immune system and eventually progress to AIDS.
There is no cure for dermatomyositis, but the symptoms can be treated. Options include medication, physical therapy, exercise, heat therapy (including microwave and ultrasound), orthotics and assistive devices, and rest. The standard treatment for dermatomyositis is a corticosteroid drug, given either in pill form or intravenously. Immunosuppressant drugs, such as azathioprine and methotrexate, may reduce inflammation in people who do not respond well to prednisone. Periodic treatment using intravenous immunoglobulin can also improve recovery. Other immunosuppressive agents used to treat the inflammation associated with dermatomyositis include cyclosporine A, cyclophosphamide, and tacrolimus. Physical therapy is usually recommended to prevent muscle atrophy and to regain muscle strength and range of motion. Many individuals with dermatomyositis may need a topical ointment, such as topical corticosteroids, for their skin disorder. They should wear a high-protection sunscreen and protective clothing. Surgery may be required to remove calcium deposits that cause nerve pain and recurrent infections.
Antimalarial medications, especially hydroxychloroquine and chloroquine, are used to treat the rashes, as they are in similar conditions.
Rituximab is used when people don't respond to other treatments.
As of 2016, treatments for amyopathic dermatomyositis in adults did not have a strong evidence base; published treatments included antimalarial medications, steroids, taken or orally or applied to the skin, calcineurin inhibitors applied to the skin, dapsone, Intravenous immunoglobulin (IVIG), methotrexate, azathioprine, and mycophenolate mofetil. None appear to be very effective but among them, IVIG has had the best outcomes.
Despite its very similar clinical presentation to PM, IBM does not respond to the drugs that effectively treat PM, and there is no proven effective therapy for IBM. Alemtuzumab is being studied but as of May 2013 it had not demonstrated clinical effectiveness in IBM. Dysphagia (difficulty swallowing) may be improved by intravenous immunoglobulin, though more trials are needed. Non-fatiguing, systematic strength-building exercise has demonstrated benefit. Occupational and rehabilitation therapists can offer good advice on walking without falling and performing fine motor tasks, and can provide appropriate canes, braces and wheelchairs. Speech pathologists can provide advice on preventing choking episodes and reducing the anxiety of an immanent aspiration for both patients and carers.
Prognosis is good with early, aggressive treatment (92% survival in one study).
Development of new therapies has been hindered by the lack of appropriate animal model systems for some important viruses and also because of the difficulty in conducting human clinical trials for diseases that are rare. Nonetheless, numerous innovative approaches to antiviral therapy are available including candidate thiazolide and purazinecarboxamide derivatives with potential broad-spectrum antiviral efficacy. New herpes virus drugs include viral helicase-primase and terminase inhibitors. A promising new area of research involves therapies based on enhanced understanding of host antiviral immune responses.
There is a vaccine for FHV-1 available (ATCvet code: , plus various combination vaccines), but although it limits or weakens the severity of the disease and may reduce viral shedding, it does not prevent infection with FVR. Studies have shown a duration of immunity of this vaccine to be at least three years. The use of serology to demonstrate circulating antibodies to FHV-1 has been shown to have a positive predictive value for indicating protection from this disease.
There is no standard course of treatment to slow or stop the progression of the disease. sIBM patients do not reliably respond to the anti-inflammatory, immunosuppressant, or immunomodulatory medications. Management is symptomatic. Prevention of falls is an important consideration. Specialized exercise therapy may supplement treatment to enhance quality of life. Physical therapy is recommended to teach the patient a home exercise program, to teach how to compensate during mobility-gait training with an assistive device, transfers and bed mobility.
Treatment is generally supportive. Rest, hydration, antipyretics, and pain or anti-inflammatory medications may be given as needed.
Herpes simplex virus, varicella zoster virus and cytomegalovirus have a specific antiviral therapy. For herpes the treatment of choice is aciclovir.
Surgical management is indicated where there is extremely increased intracranial pressure, infection of an adjacent bony structure (e.g. mastoiditis), skull fracture, or abscess formation.
The majority of people that have viral meningitis get better within 7-10 days.
Treatment is directed toward the underlying cause. However, in primary eosinophilia, or if the eosinophil count must be lowered, corticosteroids such as prednisone may be used. However, immune suppression, the mechanism of action of corticosteroids, can be fatal in patients with parasitosis.
In cases of viral pneumonia where influenza A or B are thought to be causative agents, patients who are seen within 48 hours of symptom onset may benefit from treatment with oseltamivir or zanamivir. Respiratory syncytial virus (RSV) has no direct acting treatments, but ribavirin in indicated for severe cases. Herpes simplex virus and varicella-zoster virus infections are usually treated with aciclovir, whilst ganciclovir is used to treat cytomegalovirus. There is no known efficacious treatment for pneumonia caused by SARS coronavirus, MERS coronavirus, adenovirus, hantavirus, or parainfluenza. Care is largely supportive.
In women with SS, vaginal dryness, vulvodynia and dyspareunia (painful sexual intercourse) are often reported; personal lubricants are recommended to help lessen irritation or pain that may result from dryness in the vaginal and vulva areas.
Nonsteroidal anti-inflammatory drugs (NSAIDs) may be used to treat musculoskeletal symptoms. For individuals with severe complications, corticosteroids or immunosuppressive drugs may be prescribed, and sometimes IVIG (intravenous immunoglobulin). Also, disease-modifying antirheumatic drugs (DMARDs) such as methotrexate may be helpful. Hydroxychloroquine (Plaquenil) is another option and is generally considered safer than methotrexate. However, these prescribed drugs have a range of side effects such as nausea, loss of appetite, dizziness, hair loss, stomach aches/cramps, headache, liver toxicity, and increased risk of infections. Also, people who take drugs to suppress the immune system are more likely to develop cancer later.
No treatment exists for the viral infection. Antibiotics may help prevent secondary infections.
Vaccination is available in different forms, usually for naive flocks.
Good biosecurity measures should be maintained including adequate quarantine, isolation, separation of different age groups and disinfection.
Antivirals such as acyclovir, famciclovir, or valacyclovir may be used. Intravenous acyclovir is reserved for individuals who cannot swallow due to the pain, individuals with other systemic manifestations of herpes or severely immunocompromised individuals.
There is no current cure. The only way to treat this disease is by treating symptoms. Commonly patients are prescribed immunosuppressive drugs. Another route would be to take collagen regulation drugs.