Articles on Medical Diseases and Conditions

Tag: Lyme disease

  • Lyme Disease

    Lyme disease is caused by the spirochete Borrelia burgdorferi by means of several tick vectors, the principal one in the Northeast and North Central United States being the deer tick Ixodes dammini and in the Pacific Coast states, Ixodes pacificus, the Western black-legged tick (both morphologically “hard” ticks). The three major affected areas in the United States are the northeastern states (New Jersey to Connecticut), the far western states, and the upper midwestern states. However, cases have been reported elsewhere and also in Canada, Europe, and Australia.

    Ixodes dammini has a 2-year, three-form life cycle. The very young ticks (called larval stage, although the organism has a tick shape) feed on a vector organism, usually the white-foot mouse, and then are dormant until the following spring. The larval ticks are very small and have only three pairs of legs, like insects. The following year in the spring the larval tick changes to the nymph stage, which has four pairs of legs like the adult stage.

    In 50%-80% of patients, about 1 week (range, 3-68 days) after the tick bite, a reddish macular expanding lesion with central clearing (“erythema chronicum migrans”) develops on the skin at the inoculation site often followed by similar skin lesions in some other areas. This usually fades within 2-3 weeks (range, 1 day-4 weeks) and is usually accompanied by low-grade fever, weakness, fatigue, and regional lymphadenopathy. Although this characteristic skin lesion should strongly suggest Lyme disease, only 20%-30% of patients recall such a lesion. Migratory arthralgias and myalgia are frequently present. About 10% of patients develop anicteric hepatitis. In the second stage of illness, CNS (most often aseptic meningitis) or peripheral nervous system abnormalities (Bell’s palsy or Bannwarth’s polyneuritis syndrome) occur about 4 weeks (range, 2-8 weeks) after the tick bite in about 15%-20% of patients (range, 11%-35%). About 7% (range, 4%-10%) of patients develop transitory ECG abnormalities or myocardial inflammation, usually about 5 weeks after the tick bite (range, 4 days-7 months). In the third stage of illness, about 40% (range, 26%-60%) of patients develop recurrent arthritis. This is the most famous manifestation of Lyme disease and involves one or more joints, most commonly the knee, beginning about 6 weeks-6 months after the tick bite (range, 4 days-2 years).

    Laboratory test abnormalities include elevated erythrocyte sedimentation rate in about 50% of cases. Peripheral blood WBCs are elevated in only about 10%; fluid aspirated from arthritic joints is similar to that from patients with rheumatoid arthritis. CSF in patients with meningeal or peripheral nerve symptoms usually show increased numbers of WBCs with lymphocytes predominating, normal glucose and mildly increased protein levels, oligoclonal bands similar to those of multiple sclerosis, and CSF-IgM antibody present.

    Culture can be done from biopsy of the erythema migrans (ECM) skin lesion; best results are obtained from the advancing edge of the lesion. Transport of the specimen and specimen culture in the same special BSK culture media plus incubation for several weeks if necessary has produced best results; but even so the spirochetes were isolated in less than 45% of cases (range, 5%-71%). Warthin-Starry silver stains on ECM lesion biopsy demonstrates spirochetes in less than 40% of cases. Blood cultures may be positive in the second stage of illness but only in 2%-7% of cases and therefore is not cost-effective. Culture of CSF in second-stage symptomatic patients may be positive in about 10% of patients. DNA probes with PCR amplification have been reported to have a sensitivity of 80% when performed on a biopsy of the ECM skin lesion, the same or better than the best culture results. However, thus far, DNA probe for Borrelia antigen in blood has not substantially improved serologic test results.

    Currently, the most helpful procedures are serologic tests. IgM antibody levels rise about 2-4 weeks after onset of ECM, peak about 6-8 weeks after ECM onset, and usually become nondetectable by 4-6 months after onset. However, some patients have persistent IgM levels, presumably due to continued infection or reinfection. IgG antibody levels rise about 6-8 weeks after onset of erythema migrans and peak at about 4-6 months after onset of erythema migrans, but may not peak until later or even more than a year. The highest IgG levels tend to occur when patients develop arthritis. IgG levels typically remain elevated for life. The most commonly used tests are immunofluorescent and ELISA methods. False positive results can be obtained in patients with other spirochetal diseases, such as syphilis, relapsing fever, and leptospirosis, and according to one report also in subacute bacterial endecarditis (SBE). Some of the ELISA tests attempt to adsorb out some of these antigens if they are present. Both test methods can give about the same results, although investigators generally seem to have a more favorable opinion of ELISA. In the earliest stage of the disease (ECM present 1-7 days), serologic tests are rarely positive. Later in the first stage, 3-4 weeks after onset of ECM, the tests are positive in about 40% of patients. In the second stage of illness (coincident with systemic symptoms) about 65% are positive, and in the third (arthritic) stage, about 90%-95% (range, 80%-97%) are positive. This suggests that negative serologic tests in clinical stages one and two may have to be repeated 3-4 weeks later. ELISA tests using recombinant flagellar proteins as antigen somewhat improve IgM test specificity and may increase sensitivity a little in early disease compared to ELISA tests using whole organism alone. Sensitivity of IgG antibody is significantly greater than IgM in the second and third stages of Lyme disease because disseminated (second stage) infection raises IgG more than IgM (which has already peaked or has already started to decline).

    Evaluation of different kits has shown considerable variation in sensitivity and specificity between different kits, between laboratories, and even between evaluations in the same laboratories when the same specimen was repeated later. Western blot testing is commercially available or performed with homemade reagents. This has the advantage of visually identifying which proteins are reacting to patient antibodies. Unfortunately, there still is little agreement how to interpret the Lyme Western blot test. Some of the proteins that are rather frequently detected are shared with other organisms. Some of the more specific proteins (outer coat proteins A and B) may not appear until relatively late in some patients. Nucleic acid probe testing has recently been reported, with or without PCR amplification, mostly using homemade reagents. Although results have been more sensitive than some standard ELISA or fluorescent antibody kits, DNA probes so far have not increased usable sensitivity as much as has been achieved in some other diseases. Finally, some studies have reported that some patients with Lyme disease have a reactive antinuclear body (ANA) test, usually the speckled type. One report found that the VDRL or RPR test for syphilis is usually nonreactive.

    In one report from a Lyme disease referral center, of 788 patients with positive serologic test results for Lyme disease, 23% had active Lyme disease, 20% had previous Lyme disease, and 57% were judged not to have evidence of Lyme disease.

  • The causes of Multiple Sclerosis

    The cause or causes of Multiple Sclerosis are still unknown. Although there are significant geographical variations in the distribution of people with MS throughout the world, a great deal of research has failed to uncover any tangible evidence that there are specific avoidable risk factors associated with the onset of the disease.

    Genetic versus environmental causes

    At present, the most likely cause appears to be a combination of genetic and environmental factors. Studies of identical twins, where one or both has MS, of fer what might be called the ‘purest’ way in which to investigate this theory: it appears that genetic factors contribute between
    30 and 35% and environmental factors about 65–70% of the total contribution to the cause. These two figures suggest that further research needs to be undertaken on both issues. There does not seem to be one simple gene linked to MS, but we do know, for example, that first- degree blood relatives of someone with Multiple Sclerosis, such as children and siblings (brothers and sisters), are at slightly enhanced risk of the disease.
    Amongst many other theories about the causes of MS, there has been a particular interest in the role of ‘heavy metals’. It is certainly true that an excess of some heavy metals in the body, such as lead, mercury and cadmium, may result in serious neurological damage. Lead in particular is a potential cause of neurological damage, although, with the reduction of lead in petrol, it is gradually being reduced in our environment, but at present there is no evidence that excess lead causes MS. Excess mercury can also produce neurological damage, and there has been much discussion about the possible problems with mercury-based dental fillings. However, a large proportion of the adult population will have had at least some mercury fillings in their lifetimes, and yet only a fraction of those people have MS. Dental amalgam does contain mercury which can erode over time and be absorbed into the bloodstream, but this is a very small contribution to the amount of mercury ingested by most people
    (deep-sea fish is a much greater source). The exposure to dental amalgam is well within the safety limits currently recommended for mercury.

    Infections and other diseases

    Research has not shown Multiple Sclerosis to be caused by any particular bacterial or viral infection, but it is possible that the timing of a relapse may coincide with an infection. This could be due to a change in immune activity that allows the infection to gain hold: the bacterial infection can trigger an immune response, or both the relapse and the infection may occur in response to some unknown third factor.

    Candida
    At present there is a widespread interest, particularly amongst many involved in alternative or complementary medicine, in Candida albicans (thrush). Although candida can be associated with many symptoms, as well as having a low-level but debilitating ef fect on health, there is almost no formal evidence that it is associated with relapses of MS in itself. Candida infection may be a result rather than a cause of a weakened immune system, and it is also known to be more common as a side effect of some anti-inflammatory drugs used in Multiple Sclerosis. Of course, any infection with potentially problematic symptoms should be treated with antibiotics.

    Herpes
    Amongst viruses that have prompted scientific interest in relation to MS, the herpes virus HHV-6 is one of a number currently being researched. However, as with other viral candidates for a cause of MS, this line of enquiry is controversial and much debated.

    Lyme disease
    There is no evidence that this disease, which is spread by tics living on a range of animal species in the countryside, can cause MS, although its symptoms may mimic those of MS.

    ’Flu jabs and other injections
    Many people with MS naturally look for a preceding event, such as a ‘flu jab, to explain why their symptoms have worsened, or why they have had an ‘attack’ or ‘relapse’. Research studies have failed to demonstrate any link between injections (vaccinations or inoculations) and any subsequent worsening of the MS.

    Links between MS and other conditions including cancer
    Many people with MS can point to symptoms and illnesses that seem to have preceded its onset. There is no clear definitive link that been established between the prior effects of diseases and the onset of MS. Of course as MS progresses, it may itself give rise, in ef fect, to other conditions, through a weakened immune system or just by ageing, for example.
    There is no known link between cancer of any type and MS, but it is to be expected that some people with MS will develop cancer, but no more frequently than people who do not have MS.

    Autoimmune diseases
    There are strong similarities between some aspects of other autoimmune diseases, where the immune system is triggered into mistakenly attacking normal tissues in the body, and some aspects of MS. At present these conditions are still thought to be completely separate disease entities, although it is possible that there may be some very general biological processes underlying these conditions. These processes are the object of considerable recent research.

    Stress
    Fatigue, and possibly what we call ‘stress’, could have had some effect, not as a cause of MS, but perhaps as an exacerbating factor on some symptoms. However, although most people with MS probably feel that undue stress in their lives may bring on a relapse, scientifically this issue is still being argued over. Even so, many people have their own ideas about things that they feel are linked with their Multiple Sclerosis symptoms, and try to avoid them.

    Accidents and injuries
    Studies have compared accident and injury rates in people with MS who have had relapses and those who have not. Almost all have concluded that there is no significant dif ference in rates, or evidence to support trauma as causing or worsening MS. A more general issue is whether head injuries may have broken what is called the blood–brain barrier so that some parts of the CNS may themselves become contaminated and thus be damaged by the various blood products that are released. However, the relationship of any breach of the blood–brain barrier and the onset of MS is disputed.

    Diet
    There has also been extensive scientific research on MS and diet which may have some bearing in the medium and longer term on health in general.
    There is substantial research indicating that what are called
    ‘unsaturated fatty acids’ – essential building blocks of the brain and nervous system – may be deficient in people with Multiple Sclerosis, which is why supplements containing these fatty acids have become popular. However, there is little evidence that taking supplements with the fatty acids has any major effect on MS. More generally, there is also little evidence that any particular diet has major effects on the course of MS, although some evidence suggests that a low-saturated fat diet may be beneficial as regards relapses.
    Finally, there is little or no evidence that poor diet in itself causes MS – if this were so, the geographic and social distribution of MS would be very different.