TREATMENT EFFECTS 

Numerous body changes are caused by disease and medications. (Last update 07/02/10)

• Glucocorticoid-induced
  • Prednisone or similar glucocorticoids are usually used at the time of diagnosis to quickly reduce inflammation.  There is perhaps no ways (other then some "rescue" therapies) to quickly counter inflammation and stop damage as some immunosuppressives are slow to take effect.
  • Many body changes occur when one is on prednisone for any extended time.
    • Some changes are temporary; some are permanent.
    • Some changes can be countered by medications, exercise, and life style changes.
  • Typical and common body changes that aren't very serious in themselves or can be treated effectively are:
    • acne, appetite increase, arthralgia, cataracts, constipation, Cushing's syndrome (swollen face, upper back hump), fluid retention, euphoria, hyperactivity, impaired wound healing, insomnia, muscle pain (myalgia), myopathies (muscle wasting and weakness), Petechiae (minute hemorrhages into the skin), psychological dependence, shakiness, skin atrophy, yeast infection (thrush), weight gain.
  • Some bodily changes that are more serious and require medical attentions are:
    • Adrenal insufficiency, avascular necrosis (death of tissue, often bone, due to capillary damage), depletion (of calcium, magnesium,  nitrogen, potassium, protein), increase eye pressure (predisposes to glaucoma), peptic ulcers, steroid-induced diabetes, steroid-induced osteoporosis, stunted growth in children, tooth erosion.
  • Not all persons experience all the possible changes due to prednisone.
    • Click here to view a table of prednisone effects taken from a supposed reliable source, but edited by a person with no medical training to include information on seriousness and frequency.
  • Prolonged use of prednisone can temporarily or permanently reduce adrenal gland functions, and secondarily, thyroid functions.
    • Replacement therapy may be required for hypothyroidism to avoid serious, even fatal consequences.
  • Persons who have become prednisone dependent will experience many symptoms while lowering the prednisone dosage.
    • Roving joint pains are common but usually resolve in a week or two.
  • Adolescents may experience retarded growth and may require supplementation of human growth hormone (HGH).
  • A 2008 study found increased femoral fractures due to long term use of one biphospnonatee.
  • Loss of magnesium due to prednisone may require a magnesium supplement.
• Immunosuppressive-induced
  • Infections are always a danger when on immunosuppressives.  Any sign of infection should result in a visit to your physician.  Click here to see "Infection"� in "TREATMENTS"�.
  • Immune suppression makes a patient more susceptible to infection.
    • Prophylactic antibiotics may be used to prevent opportunisitic bacterial infection.
      • Elderly patients with significant lung damage and low hemoglobin are susceptible to invasive pulmonary aspergillosis (IPA).
      • Such patients should be monitored and may require preventative treatment with prophylactic antifungal therapy.
    • See http://www.rxlist.com for side effects of various immunosuppressives. And http://www.nlm.nih.gov/medlineplus/druginformation.html
  • Malignancy
    • An autoimmune disease predisposes the patient to malignancy.
    • Approximately 5% of patients with some form of vasculitis may have a pathogenetically related malignancy.
      • A Jan. 2008 study found exposure to Cytoxan increased risks for leukemia, lymphoma, and non-melanoma skin cancer, in addition to bladder cancer.
    • A small study of long-term experience in one center discovered 12 patients in whom malignancy and vasculitis were recognized within a 12-month period.
      • The most common form of vasculitis was cutaneous leukocytoclastic vasculitis with lymphoproliferative or myeloproliferative disorders being most common.
      • It is important to note failure of vasculitis to respond to effective conventional therapy as a major diagnostic clue that a neoplastic process may be involved.
    • Opiate/narcotic pain meds can cause constipation. Some medications can help defeat constipation: Talk with your dr. first, of course. Make sure that what you plan to take is safe for you.
    • This list of pain medications list is ascending order of effectiveness:  Codeine; Hydrocodone; Oxycodone; Hydromorphone; Morphine.
    • Other pain relievers are Fentanyl patch (e.g. Duragesic) for additional continuous coverage; Neurontin or Tegretol if you have nerve pain:  NSAIDs if you have inflammatory pain: Indomethacin (Indocin) suppositories
    • Tegretol is being replaced with Trileptal, much safer as Tegretol blocks the action of many painkillers, and Trileptal has no adverse effect on the liver.
    • Don't use over-the-counter NSAIDs without your physician's approval.
    • Click here to view a table of analgesics used for pain relief. Always check with your physician before starting or changing analgesics.
  • Nausea - A variety of medications are available to help reduced nausea due to immunosuppressives.
    • Some are Ondansetron (Zofran). Dolasetron(Anzemet), Granisetron (Kytril), Palonosetron (Aloxi), Dexamethasone (Decadron), Prochlorperazine, Metoclopramide (Reglan), Haloperidol, and Lorazepam (Ativan).
    • Some are best taken before eating, some with food, etc.  Ask your physician and try different ones until you find one effective for you.
• Osteoporosis
  • Description
    • Osteoporosis is a condition where a great deal of bone mass has been lost so the person is likely to easily suffer bone fractures due to simple stress such as coughing or minor falls. Osteopenia is the condition where some bone mass has been lost, but not excessively.
    • Bone mass deficiency is referred to as BMD.  The most common causes of BMD:
      • Therapeutic dosages of glucocorticoids such as Prednisone are associated with rapid bone loss and a high risk of fracture.
      • Hormone replacement therapy (HRT) for post-menopausal women.
      • Lack of weight bearing exercise, in childhood and throughout life.
    • Click here for a tutorial on osteoporosis.
    • Click here to view an update on osteoporosis treatment as of March 2004.
    • Click here for a paper on the "Osteoporosis Revolution", dated March 1997.
  • Prevention
    • Supplemental calcium and vitamin D or D3 or alfacalcidol are often ordered to prevent bone loss for older people and those on a glucocorticoid.
      • Calcium supplements are best taken between meals as a number of foods inhibit absorption.
    • Osteoporosis is more easily prevented than reversed.
    • Exercise that puts stress on bones is useful in maintaining or improving bone strength along with appropriate supplements and medications.
      • WARNING - Prednisone weakens tendons and muscles so exercise must be limited enough to avoid damaging those.  Check with your physician about the extent of exercise permitted.
    • As phosphoric acid and/or caffeine in many soft drinks may contribute to bone loss, it might be well to consider avoiding those so not to aggravate bone loss.
    • A Mar 2009 abstract indicated combination therapy with alendronate (one of a number of biphosphonates) and alfacalcidol increases bone density and improves the biochemical markers of bone turnover, without any substantial increase in the incidence of adverse effects.  Alfacalcidol is administered orally or intravenously.
    • A patient on long term Prednisone (or similar) probably should have a bone scan done initially and annually thereafter to check for possible osteopenia or osteoporosis.
  • Medications
    • Patients with an AV are usually put on medications to diminish bone loss, often a biphosphonate.
    • WARNING - Biphosphonates have been implicated in serious bone necrosis, often in high load joints such as jaw bones (1 in 100,000).
    • In 2007, one study found the use of a parathyroid hormone, PTH, such as Forteo (Teriparatide) to be more effective than other means
    • Adult patients on Prednisone (or similar) are usually put on calcium supplements (1200-1500 mg/day) and extra vitamin D (400-800 units/day) to minimize bone loss.  Sometimes magnesium supplement is ordered. Patients are frequently instructed to take vitamin and mineral supplements as well.
    • Bisphosphonates are widely used, though gastrointestinal tolerance can be a problem with daily oral administration and newer medications are now available.
      • Click here to view a partial table of biphosphonates (May 2004).
      • Once weekly regimen is available in selected biphosphonates and can reduce adverse G/I events.
        • Injection therapies may also avoid G/I problems but sometimes introduces the smaller problem of acute phase reactions.
    • Be sure the BMD medication you are on will decrease the probability of bone fractures, not merely maintain or improve BMD.
    • Generations of biphosphonates
      • One first generation biphosphonate is Idronel (Etidronate).
      • Some second generation biphosphonates are:  Fosamax (Alendronate), Tiludronate (Skelid), Risedronate (Actonel), Aredia (Palmidronate), Clondronate.
        • Actonel has been approved (May 2002) for weekly use to treat prednisone-induced osteoporosis, and may be available as injectable for use every three months.
        • Alendronate, risedronate, and in May 2003, ibandronate medications have been demonstrated to increase BMD and reduce risk for fractures.
        • A 2007 study evaluating an active D-hormone analog, Alfacalcidol found that the combination Alendronate and Alfacalcidol was superior to Aldronate alone in maintaining bone mass, and also superior in terms of falls, fractures and back pain.
      • There is a clinical development program to evaluate monthly oral and "quarterly intravenous dosage" regimens of Ibandronate in women with post menopausal osteoporosis.
      • Third generation biphosphonates (Milodronate, Ibandronate (Boniva) and Zoledronate (Zometa).
        • Boniva is approved as a once/month treatment to prevent BMD.
        • WARNING - At least one recent report showed that a small percentage of persons on second and third generation biphosphonates suffer severe jaw necrosis (bone death).
        • Some and perhaps all biphosphonates may increase the BMD, but not reduce the incidence of fractures
      • Newer treatments for BMD include:
        • Anabolic agents such as teriparatide (PTH) and strontium ranelate have marked effects on BMD and subsequent reduction on fracture risk.
          • Forteo (Teriparatide) is a synthetic form of parathyroid hormone (PTH).  It is an injectable medication that might be used when biphosphonates are not tolerated and has been suggested as a first choice over biphosphonates.
          • Note that Forteo users should be checked for Paget's disease so that osteosarcoma won't be risked.
          • Forteo increases normal growth of new bone.
        • Promising is an anti-receptor activator of nuclear factor-kappaB ligand (RANKL).
        • Raloxifene (Evista) appears to have a superior safety profile to hormone replacement therapy (HRT).
        • While Evista prevents bone loss, it may not increase the BMD.
        •  Stem cell transplant has been used experimentallyto treat osteonecrosisof the hip.  See http://www.dailyexpress.co.uk/posts/view/130629/My-surgery-free-hip-replacement/  
        • The experimental drug PTHrP, a protein made naturally by the body, also is an anabolic agent and appears to be unique in its ability to stimulate bone formation without simultaneously increasing bone breakdown. The drug is given as daily injections.
        • Various new selective estrogen receptor modulators (SERMs) are in development to treat post-menopausal women.
          • Miacalcin is a bone-enhancing medication in the form of a nasal spray.
          • Reclast, is administered annually in a 15-minute infusion for women with post-menopausal osteoporosis.
          • While none of the above options is suitable for everyone, the range of available therapies does mean that physicians can usually find an intervention that is effective and acceptable. Raloxifene (Evista) appears to have a superior safety profile to hormone replacement therapy (HRT).
  • Neuropathy
    • Peripheral neuropathy (PN) is often damage to nerves in limbs (legs, feet, arms, hands).  About 30% of systemic autoimmune disease patients will have PN.
      • It can involve motor nerves, sensory nerves, or autonomic system nerves.
      • It can be merely uncomfortable, or very painful or weaken muscle control
      • It is often experienced as tingling, cold, burning, severe pain or numbness in limbs
      • Peripheral neuropathy can damage the autonomic system that maintains stasis in the body.   Malfunctioning can cause a variety of symptoms such as:
        • Heart rate abnormalities
        • Sudden drops in blood pressure when rising.
        • Exercise intolerance
        • Sluggish pupil response to changes in light
        • Improper gastrointestinal function
          • Peripheral neuropathy can sometimes effect stomach nerves and muscles causing nausea and/or bloating.
          • Medications may be necessary to help the stomach entrance and exit work properly. Sometimes the condition improves over time.
        • No usual signs of low blood sugar
        • Heat intolerance
        • Sexual dysfunction.
        • Urinary tract problems
      • Click here for a write-up on PN originated by a D.O. and edited by a patient.
    • Treatment
      • The best treatment for PN is to promptly treat the underlying vasculitis.
      • The most immediate help are Prednisone or similar glucocorticoid to stop progression of the vasculitis.
        • Unfortunately, glucocorticoids can weaken capillaries, so damage may occur, sometimes impeding blood flow and aggravating PN
        • For this and many other reasons, Prednisone or similar should be used only when medically necessary.
      • Physical therapy and medications may be needed.
        • Weakness may require a foot brace, walker, etc., if only temporarily.
      • If numbness develops, special care must be taken to avoid injury.
      • A 2005 study showed IVIG effective in treating some patients with peripheral neuropathy due to a primary or secondary vasculitis.
      • Some research points to use of a vascular endothelial growth factor (VEGF) as possibly effective in treating P.N.
      • Recently Rush Medical Center in Chicago has found microsurgery to be helpful in relieving the pressure on nerves in patients with diabetic PN.
        • This procedure may not be useful for persons with PN due to vasculitis.
      • Intravenous administration of  Ilomedin  (Iloprost) has been effective in some cases of diabetic PN, but might not be effective for AV-caused PN., although one case has been reported of effectiveness in restoring blood flow to extremeties (2009).
      • Lamictal (Lamotrigine) is an anticonvulsant drug used in the treatment of epilepsy and bipolar disorder, but also has been used to treat peripheral neuropathy, despite the lack of understanding functional specific.
      • Australian researchers developed a pump to increase blood flow to peripheral tissues.
        • In 2007, a Peripheral Access Device (PAD™) was implanted into the femoral artery located in the thigh.
          • The device was connected to a blood pump outside the body. It allowed simple, repeatable access to the femoral artery. This, in turn, increased the pressure of the blood flow above the blockage caused by the clot.
            • The resulting increase in blood pressure caused a 250% increase in the blood flow to the foot.
            • This also stimulated growth of new vessels into the lower limb.
          • The device may be marketed by Advanced Surgical Design and Manufacture after review and approval by various national governments.
    • Relief
      • The first category of medications for pain due to neuropathy have included various antidepressants.
        • The older ones such as amitryptiline (Elavil), doxepin, etc., can be effective as can newer ones, such as Effexor, and Cymbalta (duloxetine).
          • The latter was basically developed specifically for neuropathy.
        • Antidepressants may help depression as well be effective in treating PN.
        • Antidepressants of the SSRI type such as Prozac, Zoloft, Paxil , and Lexapro, might help the depression but don't do much for the neuropathy.
      • A second category of drugs for treating neuropathy is anticonvulsants, or anti-epileptic drugs (AEDs).
        • Although they were developed to treat seizures, they are also useful for neuropathic pain.
        • Neurontin is one that seems reliable yet there are about 20 others that have been used.
          • They each have differing chemical pathways and targets in the nervous system.
          • If one AED doesn't work, or the side effects are intolerable, try an alternative one.
          • Lyrica (pregabalin) was developed specifically for neuropathy.
            • Preliminary results suggest that it seems to be effective with tolerable side effects.
        • The AEDs should be started at a low dosage and gradually increased to avoid creating intolerable si
        • Trental (marketed as Pentoxil (Upsher Smith), Pentoxin (Ratiopharm), and Artal (Leiras) may improve peripheral blood flow, but has not been widely used for peripheral neuropathy.
      • A 2004 report said evidence from clinical trials supports the use of amitriptyline (Elavil), capsaicin, tramadol (Ultracet, Ultram), gabapentin (Neurontin), bupropion (Wellbutrin, Zyban), venlafaxine ((Effexor)as preferred medications.
      • Aches and Pains Away' is an herbal spray (Ausralian?) containing capsaicum and it does give some relief.  The other thing that can give relief is to wrap the affected area (eg feet) in cling wrap (the type of thing you wrap food in).
      • Topical treatments
        • Ketamine is available as a cream that can sometimes have real benefit on neuropathic pain.
        • Other medications available for topical use include Lidocaine , a numbing medication, available commercially in patches (Lidoderm) which are often very helpful, or in combination with other medications often tried for neuropathic pain, such as clonidine, antidepressants, anticonvulsants, anti-inflammatory medicines, muscle relaxants, etc.)
        • The problem with topical medications is that have to applied on the painful area, so if large areas of the body are burning, they aren't feasible alternatives.  The side effects of using them externally are less than taking them by mouth.
          • Anecdotal reports say that Vicks VapoRub on feet and legs can bring some relief.
    • Research
      • Research is on-going for new medications, treatments, and ways of helping the nervous system repair itself.
        • New ideas using hormones, growth factors, cell building enzymes, stem cells, etc. are being explored.
        • It is important to keep a positive attitude as there will be better modes of treatment in the future.
        • More physicians have come to understand PN, and are better prepared to help their patients.  More psychologists and other therapists are becoming available to help use the mind's ability to make anti-pain chemicals.
        • A recent study (2005) showed that a combination of morphine and Neurontin allowed lower dosages of both and was more effective at reducing pain of peripheral neuropathy than either used alone at higher dosages.
        • Tramdol (Ultram & Ultracet) have also been recommended for PN pain though with perhaps unknown effectiveness.
          • Tramdol is a non-narcotic pain reliever, but dependence can occur.
        • Single or multiple mononeuropathy associated with CSS and MPA of vasculitis can often be painless.
    • Analgesics
      • Analgesics can help with pain but not inflammation.
      • Ask your physicians about using analgesics if you can to avoid NSAIDS if possible.
      • Click here for information on analgesics.
   
  • Ulcerations
    • Infected ulcerations must be treated aggressively as they constitute a serious danger to the peripheral limbs.
    • Patients with ulcerations might do well adding a wound specialist to their team of physicians.
    • Ulcerations aren't unusual with disease that impede blood flow to the periphery.
    • When ulcerations are slow to heal, use of hyperbaric oxygen may be helpful.
    • Some have found relief using silver nitrate sticks to coat the ulcer.  Check with your physician before using.
    • A slow-release formula of basic fibroblast growth factor incorporated in biodegradable gelatin hydrogel has been administered into calf muscles to induce vascular regeneration. The ulcer eventually healed with no recurrence.  [CSS patient]
    • An expensive cream, Regranex, may be effective.
    • An (experimental) drug that may help is Pletal (used for relief of claudication) but don't consider usage  without your physician's approval.
    • Sometimes mouth ulcers are a side effect of methotrexate.
      • Added folic or folinic acid in the diet or by supplement may help, but ask your physician.
  • Avascular necrosis
    • Avascular necrosis (AVN) is death of tissue due to poor circulation.
    • Autoimmune vasculitis patients sometime experience AVN in the femur head.
      • The head of the femur bone in the hip socket is the usual area to fail due to the high compressive stress at that location.
      • This occurs sometimes when persons are on a Prednisone or similar for extended periods as they make capillaries fragile due to the high pressures.
      • Vasculitis itself may cause AVN in other organs or tissues.
    • Core decompression of the bone may help at least for a time.
      • That involves drilling holes into the bone to allow the dead bone to cleaned out so the bone can heal by providing new blood supplies to the damaged area.
    • If AVN is in the early stages, free vascularized fibular grafting (FVFG) can be done.  In the FVFG process, blood rich bone harvested from the patient is grafted into the damaged area.  If successful, this can postpone hip replacement.
    • Click here to view an html file on avascular necrosis.
  • Stenosis
    • Narrowing of the trachea below the glottis (the valve that closes the airway when swallowing) is fairly common with WG and perhaps occasional with other AVs and is known as sub-glottal stenosis.
    • Limitations in the air passages from the trachea to the lungs (bronchi) is bronchial stenosis.  It can result from WG and due to conditions other than an AV.
      • Other than WG, there are other perhaps less common causes of sub-glottal stenosis:  relapsing polychondritis, amyloidosis.
      • Perhaps the most common cause is prolonged intubation.
    • Treatment involves physical manipulations, sometimes surgery, and sometimes medicinal treatment in the form of a locally injected steroid or possibly topical mitomycin C.
    • Click here to download a June 2007 .pdf file on the subject of treating SGS and bronchial stenosis: "Tracheobronchial Wegener's Granulomatosis steroid therapy For airway compromise due to tracheobronchial Wegener's Granulomatosis"�.
    • SGS can cause rather thick mucosal secretions. Nebulized Mucomyst and oral Guafenesin may be effective in clearing the thickened "gunk".
    • Multiple endoscopies or intubation may aggravate stenosis.
    • The following seem to be the ways that subglottal stenosis (narrowing of the trachea) has been treated:
      

  TABLE 5 - TREATING SUBGLOTTAL STENOSIS

  METHOD	COMMENT
  DILATION	Often requires repeated dilations
  DILATION followed by local injected or topical steroid	Often requires repeated treatments
  # DILATION followed by local injected steroid & topical application of mitomycin-C	Seems to be the current (2007) general practice
  DILATION with local injection of anti-CD25	Report of effective results on 6 patients
  DILATION with stent tube	SILASTIC or equivalent
  LASER SURGERY	Perhaps being used less than in past.  Can cause scar tissue build-up
  ## TRACHEOTOMY & Placement of trach tube	Increases possibility of infection Resorted to only when other methods involving repeated dilations fail
  SURGICAL RESECTION/RECONSTRUCTION

  # Mitomycin C is a chemotherapy drug.  It works by sticking the cell's DNA (the cell's genetic code) together so that it can never come apart again.  This prevents cell reproduction.)

  ##  After placement of a trach tube, some patients have difficulty speaking or swallowing. The Passy-Muir Speaking Valve fits on the end of the tube or the vent.  It is a one way valve that allows effortless speech because the exhaled air can only be directed through the upper airway.  It can also help with pharyngeal pressures during swallowing

  • Students
    • Click here to download a Word brochure on AV and educational issues regarding students being treated with immunosuppressives and glucocorticoids.
    • Click here to view guidelines for students with vasculitis.

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”.
• 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.
  • Click here to view a web page listing all the links and files from this page.
• Tables & Figures – Vasculitis related
  • Click here to view a listing of the tables and figures in this web page.
• 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. 

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