TREATMENTS
- General (Last update 29 June 2010)
- Click here to view a Physician's view of autoimmune (lupus) treatment.
- Infection - Most treatments used tend increase the chances of opportunistic infection.
- Crisis - Click here to see "Crisis Treatments".
- Before 1973, there was no really satisfactory treatment for most AVs.
- Glucocorticoids such as Prednisone were used, but with serious side effects.
- Prognoses were dismal at best.
- The purpose of treatments is to reduce inflammation and reduce the number errant immune system white blood cells (WBC).
- Now, most AV cases today are at least controllable, and can usually be put into remission.
- Fauci regimen was introduced in 1973 and greatly increased survival and reduced morbidity (damage).
- Treatment as originated Dr. Fauci at the National Institutes of Health (NIH) used an immunosuppressive (IS) such as cyclophosphamide such as Cytoxan (CTX) and a glucocorticoid (often Prednisone).
- Both were continued for about one year after the disease went into remission., but not less than two years in toto.
- The Fauci regimen or modifications of it have proven successful in treating a number of AVs.
- The purpose of the immunosuppressive is to reduce the white blood cell count (WBC).
- For some AVs, it is the eosinophil count that needs to be suppressed.
- For WG, it is usually the neutrophils that need to be reduced, but rarely, eosinophils may also be involved.
- Children and adults below age 22 probably require a modified medication regimen considering their stage of growth.
- Cytoxan can be administered in daily oral doses or intravenously in periodic treatments. A Sept. 2007 article announced a study showed periodic IV to be at least as successful in getting vasculitis into remission and daily oral.
- To help prevent cystitis, some physicians prefer intravenous injection of Cytoxan periodically, rather than daily oral doses.
- The effectiveness of daily oral versus periodic intravenous administration of Cytoxan is a matter of medical discussion. There are studies both supporting and denying the equivalent effectiveness of the two methods.
- To help prevent cystitis, some physicians prefer intravenous injection of Cytoxan periodically, rather than daily oral doses.
- Unless the patient has restrictions on fluids due to poor kidney function, the patient should drink 64 ounces of water daily.
- Sometimes Mesna is prescribed when taking oral or pulsed Cytoxan to help avoid bladder cystitis and irritation.
- Lupron (Leuprolide) may be prescribed to prevent loss of fertility for women by preventing ovulation while on Cytoxan.
- Cytoxan or other non-biological immunosuppressive may require some 4-6 weeks to reach full effectiveness by suppressing white blood cell counts.
- There are risks and side effects. See Side effects below.
- Exercise done moderately can be an important part of therapy as long as done with the physician's approval.
- Prednisone and similar weaken tendons and muscles, so excessive stress must be avoided while on prednisone.
Adjusted Dose of Cyclophosphamide for Renal Dysfunction Creatinine clearance rate (ml/min) # Cyclophosphamide dose(mg/kg/day) >100 2.0 50-99 1.5 25-49 1.2 15-24 1.0 <=15 or on dialysis 0.8 # Creatinine clearance rate (CCR) is calculated by the Cockgroft-Gault equation:
In men: CCR= (140 - patient's age) - weight (in kg)/(72 x serum creatinine)
In women CCR = [(140 - patient's age) - weight (in kg)/(72 x serum creatinine)] x 0.85 - Glucocorticoids
WARNING - Persons on glucocorticoids such as prednisone should have their medical condition clearly noted in purse or wallet. It is rather dangerous for a person on steroids to miss a scheduled dosage.- Prednisone is a common glucocorticoid in use to treat AVs. It is the most common way to quickly reduce inflammation regardless of cause
- A wide variety of glucocorticoids are available with perhaps somewhat differing effects.
- There are perhaps no ways (other then "rescue therapies") to so quickly counter inflammation and stop damage as immunosuppressives and biological meds can be slow to take effect.
- Both intravenous and oral forms are available under a variety of trade names.
- Note that in subsequent sections, the term "prednisone" is used to indicate a variety of glucocorticoid formulations such as prednisone and prednisolone, etc.
- Prednisone is often started at 1 mg/kg of body weight, or about 60 mg for a person weighing about 130 lbs.
- For serious conditions, the usual dosage may be doubled for a time.
- For crises, as much as 1000 mg of prednisone (or equivalent) may be given for a brief period (1-3 days).
- Side effects are considerable, both short and long term.
- Go to "TREATMENT EFFECTS" in the navigation bar to view information on side effects of prednisone and similar glucocorticoids.
- Entocort is a "nonsystemic corticosteroid that is released into the intestine andworks to reduce inflammation. Because 90% of the drug is released in the intestine and not into the bloodstream, it causes fewer side effects than other corticosteroids.
- Prednisone dosage must be tapered slowly to avoid relapse, perhaps no more than 10% per month below 20 mg/day.
- Massive use of prednisone is common for controlling relapse of vasculitides, but this increases the risk of intestinal perforation. A prompt switching to alternative drugs when intestinal tract is involved should be considered in order to prevent surgery.
- Prolonged use of prednisone can temporarily or permanently reduce adrenal gland functions, and secondarily, thyroid functions.
- Replacement therapy may be required if the thyroid function is depressed.
- Persons who have become prednisone dependent will experience many symptoms while lowering the prednsone dosage.
- Click here to view a table of glucocorticoid equivalent dosages.
- Prednisone is a common glucocorticoid in use to treat AVs. It is the most common way to quickly reduce inflammation regardless of cause
- Clinical Studies
- For persons with no or limited medical insurance, the National Institutes of Health had on-going clinical studies.
- If an AV patient qualifies, it's usual for most medical expenses associated with the clinical trial to be paid while in the study.
- As of 31 December 2004, the NIAID has dropped some of their vasculitis clinical trials, but continue research through funding of the Vasculitis Clinical Research Consortium (VCRC).
- The VCRC will serve physicians with the latest treatment options. See the VCRC web page at http://rarediseasesnetwork.epi.usf.edu/vcrc/ While there, be sure to register, as AV patients are or will be able to get information on their disease, treatments, and clinical trials.
- The VCRC is a resource for researchers of six different vasculitides including:
- Churg-Strauss Syndrome (CSS)
- Giant Cell Arteritis (GCA/TA)
- Microscopic polyangiitis (MPA)
- Polyarteritis nodosa (PAN)
- Takyasu's arteritis (TAK)
- Wegener's granulomatosis (WG
- Precautions
- WARNING - Persons on Prednisone and similar should have their medical condition clearly noted in purse or wallet. It can be life-threatening for a person on steroids to miss the required dosages.
- WARNING - When traveling, always have several extra days of medications with you so you won't be short of medications should something keep you from returning home.
- WARNING - Glucocorticoids such as Prednisone are contraindicated in the presence of diabetes that is out of control, when there is active gastrointestinal bleeding, in the presence of psychoses induced by steroid use, and in uncontrolled hypertension.
- WARNING - Frequent measurements of blood cell counts must be ordered regardless of the immunosuppressive used to treat the patient. This is to assure the patient doesn't become highly susceptible to infection due to excessive suppression of lymphocytes (white blood cells).
- Check with both physicians and pharmacists before changing medications or dosages, or when adding or stopping supplements.
- Click here to read about avoiding infection.
- Click here to view a page on vaccinations for immunocompromised adults.
- Some AV patients find it sensible to register with MedicAlert where a single phone call by emergency personnel can access the patient's medical history, diseases, and medications before treating the patient.
- Emergency personnel are trained to look for bracelets or necklaces and in wallets and purses to find the needed contact information.
- One's "Advance Directive" regarding resuscitation can also be registered for an added fee.
- In case a patient is unconscious or unable to communicate, one can help the paramedics contact to designated person(s) happen more quickly by using "ICE" method.
- ICE stands for "In Case of Emergency". Put an entry in the contacts list in the patient's cell phone under ICE, with the name and phone number(s) of the person(s) that the emergency services should notify.
- Paramedics will examine a victim's cell phone for the ICE listing and for information on who should be contacted.
- Using ICE, paramedics can contact the appropriate party quickly. Using ICE may save future grief and possibly lives.
- One can even put in ICE1 and ICE2 for paramedics to reach two different parties.
- Emergency personnel are trained to look for bracelets or necklaces and in wallets and purses to find the needed contact information.
- Side effects
- Cytoxan can and often does have serious side effects, including female and at times male sterility.
- Glucocorticoids such as Prednisone have serious short and long term side effects.
- Long term use of a Prednisone and similar can have serious side effects, both short and long term.
- It will cause bones to weaken, inducing osteopenia or osteoporosis.
- Long term use will also weaken muscles and tendons, making injuries more likely.
- Long term use predisposes one to avascular necrosis (death of tissues due to poor blood flow)
- Click here to view a patient prepared file of information on avascular necrosis (AVN), that is, bone destruction due to glucocorticoids such as Prednisone or similar use
- The head of the femur is particularly subject to AVN
- Long term use of a Prednisone and similar can have serious side effects, both short and long term.
- Periodically, have your pharmacist review a complete list of your medications and supplements to identify any possible incompatible ones.
- Infection
- Persons with active infections of any kind should receive appropriate antibiotics and care, preferably before starting an immunosuppressive (including prednisone).
- Most of the treatments for AVs are effective by reducing either all, or specific kinds of white blood cells. That makes patients liable for opportunistic infections.
- To avoid infections, some of the recommendations are:
- Wash hands frequently
- Avoid touching face, nose, eyes, mouth
- Carry and use hand-sterilizing lotions
- Consider wearing a surgical mask if one must endure crowded situations such as airplane travel
- Avoid crowded indoor places
- Avoid obviously ill people
- Avoid cuts and abrasions.
- Use an electric razor rather than the usual blade type
- Don't share towels or bedding
- Use hot water in preference to warm or cold when washing clothes and other fabrics
- To avoid infections, some of the recommendations are:
- Persons taking immunosuppressives should take special care to guard against dental infections.
- Many physicians and dentists prescribe 2000 mg of amoxicillin one hour before any dental work, including routine cleaning for persons on immunosuppressives.
- Alternatively, for those allergic to penicillin, clindamycin can be prescribed.
- See the latest recommendations at
- All persons taking immunosuppressive medications should have a TB test prior to starting the medication if they've never been tested for TB exposure.
- Persons who have tested positive in the past for TB by means of a skin test should probably NOT repeat the test.
- Immunosuppressed persons should report any infections whether existing or newly acquired to their physician for treatment as soon as possible.
- An outbreak of shingles must be treated within 24-48 hours with the appropriate anti-viral medication to avoid what can be excruciating pain..
- Persons taking long-term immunosuppressives should perhaps request an annual purified protein derivative (PPD) testing to detect latent infections.
- Bactrim DS (Septra/Septrin) is frequently used to prevent opportunistic bacterial and protozoan infections such as pneumocystis carnii pneumonia (PCP) in other AV patients.
- Significant hypersensitivity is a known frequent side effect.
- For persons allergic to sulfa compounds, it may be possible to desensitize by following a protocol such as the one at http://depts.washington.edu/madclin/providers/protocols/bactrim.htm
- It is important to monitor blood counts closely if using the combination of Methotrexate and Bactrim, as this may lead to severe bone marrow depression.
- For patients who are unable to take Bactrim or similar formulations for prevention of PCP, or for strains resistant to Bactrim, there are alternatives:
- Dapsone
- Pyrimethamine
- Pentamidine
- Atovaquon
- Antibiotic research is on-going so there may be newer antibiotics from time to time.
- Unfortunately, none of the alternative antibiotics listed are as effective as TMP-SMX for the prevention of PCP, but do offer a significant benefit.
- Persons using Bactrim, Mepron (Atovaquone) or Dapsone to prevent PCP should know these may not always be effective against some strains of Staphylococcus aureus, the bacteria that has been identified as being associated with relapses of WG.
- Paradoxically, corticosteroids have been found to improve the ability of TMPSMX or pentamidine to treat PCP.
- Bactrim is effective with most strains of S. aureus but not MRSA or XRSA.
- A newer antibiotic for treating MRSA might be the Linezolid (Zyvox).
- New antibiotics in development may prove effective as a prophylactic for PCP and other common bacterial diseases.
- Platensimycin is a new class antibiotic for use against MRSA and some other infectious bacteria. It is still in development, and not currently available.
- Telavancin is a lipoglycopeptide antimicrobial agent in Phase III clinical trial for use in the treatment of multidrug-resistant gram-positive infections including staphylococcus aureus.
- Fungal infections
- Treatment regimens leave patients subject to opportunisitc fungal infections. For some information on fungal treatments, click here to download an Adobe Acrobat pdf file for some information on anti-fungal treatments.
- A 2009 case combined use of two antifungal agents (micafangin and itraconazole) was effective against severe aspergillosis of the bilateral pleural cavities in a 48-year old male patient diagnosed with Wegener's granulomatosis.
- Modified Regimens
- Current medical practice (2010) seems to be to prefer pulsed monthly intravenous injections of cyclophosphamide rather than daily oral as this minimizes the cumulative dosage so minimizing the long term damage. Click here to view a table on calculating intravenous dosages.
- Due to deleterious side effects of immunosuppressives and Prednisone and similar, physicians usually try to minimize the exposures to the more harsh immunosuppressive such as cytoxan and also to limit use of Prednisone and similar to that minimally required.
- Their caution sometimes causes physicians unfamiliar with AVs to not be sufficiently aggressive enough in treatment.
- A 2005 study suggested that Prednisone or similar along with intravenous cyclophosphamide (Cytoxan) followed by maintenance with azathioprine (Imuran) or methotrexate (MTX) is an effective therapeutic strategy for ANCA autoimmune systemic vasculitides and seems worthy of consideration for other AVs.
- Methotrexate use as initial immunosuppressive is perhaps generally restricted to induction of remission in patients without kidney impairment but some physicians will use methotrexate if kidney damage isn't severe.
- Another study showed that for ANCA vasculitis patients receiving MTX as a primary immunosuppressive, relapses were more frequent even though the rate of initial remission was about the same.
- Methotrexate appears to be a folic acid antagonist, so physicians usually prescribe folic or folinic acid for patients on methotrexate.
- The study further noted that, although not statistically significant, MTX appeared to be associated with more frequent adverse events than azathioprine.
- MTX (Methotrexate) has a long history with rhumatological diseases including joint diseases lke Rhumatoid Arthritis etc.. MTX can be taken by pill or by injection. Injectons can be done at home.
- WARNING - Definitely report any new or worsening symptoms to your physician. No alcohol can be taken while on MTX. MTX is processed in the liver and mixed with alcohol it can be deadly.
- Recent studies suggest that for patients with PR3-ANCA associated vasculitis who are still ANCA positive at the moment of treatment switch, the change from cyclophosphamide to azathioprine after 3 months of in remission may result in increased possibility of relapse, although this conclusion is perhaps premature.
- A November 2008 report suggested guidelines for use of MTX (in treatment of Rheumatoid Diseases.
- For patients starting MTX therapy, work-up should include clinical evaluation of risk factors for MTX toxicity, including alcohol intake; patient education; levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), albumin, complete blood count (CBC), creatinine; and chest radiographic examination obtained within the previous year. Serology for HIV, hepatitis B and hepatitis C, blood fasting glucose levels, lipid profile, and pregnancy test should also be considered.
- Oral MTX should be initiated at 10 to 15 mg/week. Depending on clinical response and tolerability, the dose should be escalated by 5 mg every 2 to 4 weeks up to 20 to 30 mg/week. For patients with inadequate clinical response or intolerance, parenteral administration should be considered.
- Prescription of at least 5 mg/week of folic acid given with MTX treatment is strongly recommended.
- When MTX is started or the dose is increased, ALT levels with or without AST, creatinine, and CBC should be checked every 1 to 1.5 months until a stable dose is reached, and every 1 to 3 months thereafter. At each visit, clinical evaluation should determine adverse effects and risk factors.
- If there is a confirmed increase in ALT/AST levels at more than 3 times the upper limit of normal (ULN), MTX should be stopped. After normalization, MTX may be reinstituted at a lower dose. If the ALT/AST levels are persistently elevated up to 3 times the ULN, the MTX dose should be adjusted. If ALT/AST levels are persistently elevated more than 3 times the ULN after discontinuation of MTX, diagnostic procedures should be considered.
- MTX is appropriate for long-term use because of its acceptable safety profile.
- In DMARD-naive patients, the balance of efficacy or toxicity favors MTX monotherapy vs combination with other conventional DMARDs. When MTX monotherapy does not control the disease, MTX should be considered as the foundation for combination therapy.
- MTX is a steroid-sparing agent that is recommended in giant-cell arteritis and polymyalgia rheumatica. It may also be considered for treatment of patients with systemic lupus erythematosus or (juvenile) dermatomyositis.
- In patients with RA who are undergoing elective orthopaedic surgery, MTX can be safely continued in the perioperative period.
- For at least 3 months before planned pregnancy, MTX should not be used for both men and women. MTX should not be used during pregnancy or breast-feeding.
- Other Immunosuppressives
- There are alternative immunosuppressives available for autoimmune vasculitis patients who can't tolerate Cytoxan or Methotrexate.
- Click here to view a document with some brief information on the mechanisms of immunosuppressives.
- A late 2006 study showed azathioprine (Imuran) to be effective in getting the disease into remission in some WG patients.
- The study showed that patients who had earlier been on cyclophosphamide found their disease responded better than those who had never been on cyclophosphamide.
- There were significant numbers of relapses even in the group that had received cyclophosphamide previously.
- Renal toxicity has been reported in renal patients.
- Studies in 2003 and 2005 reported limited successful treatment of refractory ANCA positive vasculitis with 15-Deoxyspergualin.
- A derivative (LF-0195) has been considered but whether actually used is doubtful.
- In 2007, a prospective clinical trial was announced using DSG to treat refractory WG.
- Apparently the medication isn't available outside Japan excepting for research.
- The manufacturer is the Japanese company, Euro Nippon Kayaku's trade name is Gusperimus.
- In February 2008, the Vasculitis Clinical Research Consortium announced study #5522 - A Multi-Center, Open-label Pilot Study of Abatacept (CTLA4-lg, Orencia) in the Treatment of Mild Relapsing Wegener's Granulomatosis (WG).
- In a Lund University study, the finding of low IL-10 levels are associated with relapse tendency and evokes interest in exploring its therapeutic potential.
- Click here for Table 9, a table of various medications in development that might be useful to treat AVs.
- The table was compile by a non-medically trained person and only occasional updates and corrections were made since mid-2005.
- Undoubtedly development has stopped on some, and some that get approved may not be useful to treat AVs.
- Other Glucocorticoids
- There are alternative glucocorticoids available for patients who can't tolerate prednisone.
- Both intravenous and oral forms are available under a variety of trade names.
- Equivalent dosages vary among the various formulations.
- Click here to view Table 7 of prednisone side effects from a believed reliable source.
- The designations as "common"ť and "serious"ť were assigned by a person with NO medical training based on personal and others experiences..
- In Europe where prednisolone is often used, a particular brand of prednisolone called Deltacortril is often used, because it has a special coating that reduces the possibility of stomach upset.
- A 2005 article reported on newer steroids being developed that may have fewer side effects than the common glucocorticoids. Currently under development are:
- Selective glucocorticoid receptor agonists (SEGRA or dissociating glucocorticoids)
- Nitrosteroids
- Long-circulating liposomal glucocorticoids
- Membrane-bound glucocorticoid receptors as possible further targets for specific glucocorticoid actions.
- Lodotra may be approved by the FDA as a slow-release form of prednisone that maintains more even blood levels.
- Prednisone rather quickly reduces inflammation, within days.
- In serious cases of G/I damage due to prednisone, an intravenous form may be used.
- A preventative for stomach pain due to prednisone might be carafate which is very easy to tolerate and few side effects.
- Adolescents using a glucocorticoid may be subject to restricted growth.
- Supplementation with human growth hormone (HGH) may be required.
- Membrane-bound glucocorticoid receptors as possible further targets for specific glucocorticoid actions.
- Researchers are pursuing development of a medication that will selectively provide inhibition of inflammation without the serious side effects of the glucocorticoids.
- There are alternative glucocorticoids available for patients who can't tolerate prednisone.
| #### Cellcept (Mycophenolate Mofetil) | ### Cyclosporin (Sandimmune,Neoral, SangCya) | ## Imuran (Azathioprine) | ##### Mizoribine (Bredinin). |
| # Arava (Leflunomide) | Etoposide (VP-16, VePesid) | Leukeran (Chlorambucil) |
# The Federal Drug Administration has warned of liver damage using Arava. Arava is an inhibitor of pyrimidine synthesis.
## TPMT Liver functions should be checked before starting Imuran. TPMT stands for thiopurine S-methyltransferase and is the primary enzyme responsible for thiopurine drug-based metabolism (Imuran/azathioprine is a thiopurine drug). If a patient has low TPMT enzyme activity they are at high risk for dosage-related side effects. The test is TPMT Mutation Analysis.
### The FDA warns a small percentage of patients on cyclosporin will develop kidney damage. The early formulation was named Sandimmune. Later versions are Neoral and SangCya.
#### A June 2008 FDA bulletin warned of progressive multifocal leukoencephalopthy(PML) in one patient treated with Cellcept.
##### An immunosuppressive isolated in Japan from a mould Eupenicillium brefeldianum (requires dialysis).
| Mercaptopurine (Purinethol) | Tacolimus ### (Prograf, FK-506 | Sirolimus (Rapamune) | Anti-IL-10 | Azulfidine (questionable) | Certican (Everolimus) |
### If Tacrolimus or Cyclosporine are used, a small percentage of patients will suffer kidney damage.
THIS SITE
- Intent
- To assist vasculitis patients in getting early diagnoses, effective treatments, and to advise of patient, organization, and scientific resources concerning vasculitis.
- Sources Used
- The following information is derived from a variety of sources over some ten+ years and is not to be considered as medical advice, but merely the opinions or experiences or findings of the writer who is not a physician and has no medical training.
- Much comes from Medline abstracts and medical journal articles on vasculitis. Some is from autoimmune vasculitis patients and carers, some from newsgroups, internet web pages, etc. that also deal with vasculitis.
- The compiler has attempted to use only recent valid medical information regarding vasculitis, but cannot guarantee the validity nor the currency in every case
- Limitations
- No medical decisions should be made on the basis of information on this web page or on associated linked documents and web pages unless those are from a recognized medical professional or professional medical publication.
- Limits to this web page concerning vasculitis:
- The author/compiler/editor of this web page and related pages has had NO medical training.
- Only autoimmune vasculitides will be considered, not hypersensitivity vasculitis nor vasculitis as a result of an allergic reaction to medication or vaccine..
- Most sections apply to most autoimmune vasculitides.
- One refers specifically to Wegener’s granulomatosis.
- Terminology
- Some abbreviations and equivalencies are:
- Hereafter, “autoimmune vasculitis” may be abbreviated “AV” or “AVs” for plural.
- The term “Prednisone” is sometimes used where it or a similar glucocorticoid might be prescribed to treat vasculitis.
- “Immunosuppressives” used to treat vasculitis are sometimes abbreviated “ISs”.
- Some abbreviations and equivalencies are:
- Updates
- This update was on June 1, 2009 and is a complete rewrite of the former web page at http://www.wegenersgranulomatosis.net that also dealt with vasculitis.
- Files & links – Vasculitis related.
- Tables & Figures – Vasculitis related
- Disclaimer
- ALL MEDICAL QUESTIONS, SYMPTOMS, CONCERNS AND PROBLEMS SHOULD BE DIRECTED TO APROPRIATE LICENSED MEDICAL PROFESSIONALS.
- The writer/editor/compiler does not vouch for the accuracy, completeness, nor applicability of the information included on this site to any person, whether a vasculitis patient or otherwise.Â
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