SORTING OUT LYME AND ASSOCIATED CO-INFECTIONS Joseph J. Burrascano, Jr., M.D. In addition to Borrelia burgdorferi (Bb), ticks may carry and transmit other infections. Furthermore, patients with disseminated Lyme complicated by these co-infections are usually immunocompromized and may also manifest signs and symptoms of reactivated latent infections and opportunists. All can add to morbidity and may need to be treated. Because of the large number of these other infections, the cost of reliably testing for all of them as a matter of routine is prohibitive. Also, as in the case with Bb infection, laboratory tests for them are often insensitive. Thus there is a need to sort it all out clinically to provide guidance in testing and treatment. Here are some clues: CLASSIC LYME (Bb infection)- ??Gradual onset of initial (viral-like) symptoms- this often makes it difficult to pinpoint when the infection began ??Multisystem- almost always, in disseminated stages, involves more than one part or system (i.e. joint pain plus cognitive dysfunction). ??Migratory- first a knee will hurt, then over time this may lessen and the elbow or shoulder acts up, and later the joints calm down but headaches worsen. ??Stiff joints and loud joint crepitus, especially the neck (“Lyme shrug”). ??Headaches are often nuchal and associated with stiff, painful and crepitant neck. ??Afternoon fevers, often unnoticed- most Lyme patients have subnormal temperatures in the AM but rise to 99+ by early to mid-afternoon. No obvious sweats. ??Tiredness and limited stamina- often is a strong need to rest or even nap in the afternoon, especially when the flushed face and elevated temperature appears. ??4-week cycles- Bb activity, and thus symptoms, wax and wane in a cycle that repeats roughly every four weeks. This cycle, if clear, can guide your treatments. ??Slow response to treatment, with an initial symptom flare in most (“Jarisch-Herxheimer-like reaction”) then improvement over weeks, punctuated by the monthly symptom flares. Likewise, if treatment is ended too soon, an initial period of well-being will gradually, over a few weeks, be replaced by a return of symptoms. ??EM rash in 25% to 50% BARTONELLA & ”BARTONELLA-LIKE ORGANISMS”- ??Gradual onset of initial illness. ??CNS symptoms are out of proportion to the musculoskeletal ones- if a patient has no or minimal joint complaints but is severely encephalopathic (see below), then think of Bartonella/BLO. ??Obvious signs of CNS irritability can include muscle twitches, tremors, insomnia, seizures, agitation, anxiety, severe mood swings, outbursts and antisocial behavior. ??GI involvement may present as gastritis or abdominal pain (mesenteric adenitis). ??Sore soles, especially in the morning. ??Tender sub-cutaneous nodules along the extremities, especially outer thigh, shins, and occasionally along the triceps. ??Occasional lymphadenopathy. ??Morning fevers, usually around 99. Occasionally light sweats are noted. ??Elevated vascular endothelial growth factor (VEGF) occurs in a minority, but the degree of elevation correlates with activity of the infection and may be used to monitor treatment. ??Rapid response to treatment changes- often symptoms improve within days after antibiotics are begun, but relapses occur also within days if medication is withdrawn early. ??May have papular or linear red rashes (like stretch marks that do not always follow skin planes), especially in those with GI involvement. BABESIA SPECIES- ??Rapid onset of initial illness, often with sudden onset of high fever, severe headaches, sweats and fatigue, thus it is easy to know when infection began. ??Obvious sweats, usually at night, but can be day sweats as well. ??Air hunger, need to sigh and take a deep breath; dry cough without apparent reason. ??Headaches can be severe - dull, global (involves the whole head, described like the head is in a vise). ??Fatigue is prominent, does not clear with rest, and is made worse with exercise. ??Mental dullness and slowing of reactions and responses. ??Dizziness- more like a tippy feeling, and not vertigo or purely orthostasis. ??Symptoms cycle rapidly, with flares every four to six days. ??Hypercoaguable states are often associated with Babesia infections. ??Rarely, splenomegaly ??Very severe Lyme Disease can be a clue to Babesia infection, as it will make Lyme symptoms worse and Lyme treatments less effective. EHRLICHIA/ANAPLASMA- ??Rapid onset of initial illness with fever, headache, prostration. ??Headaches are sharp, knife-like, and often behind the eyes. ??Muscle pain, not joint pain, and can be mild or severe. ??Low WBC count, elevated liver enzymes, and (rarely) inclusions seen in the WBCs. ??Rarely see diffuse vasculitic rash, including palms and soles (less than 10%). ??Rapid response to treatment. DNA VIRUSES (HHV-6, EBV, CMV) ??Persistent fatigue, made worse with exercise. ??Sore throat, lymphadenopathy, and other viral-like complaints. ??May see elevated liver enzymes and low WBC counts. ??Autonomic dysfunction. BARTONELLA-LIKE ORGANISMS It has been said that Bartonella is the most common of all tick-borne pathogens. Indeed, there seems to be a fairly distinct clinical syndrome when this type of organism is present in the chronic Lyme patient. However, several aspects of this infection seem to indicate that this tick-associated strain of Bartonella is different from that described as “cat scratch disease”. For example, in patients who fit the clinical picture, standard Bartonella blood testing is commonly non-reactive. Furthermore, the usual Bartonella medications do not work for this- they suppress the symptoms but do not permanently clear them. For these reasons I like to refer to this as a “Bartonella-like organism” (BLO), rather than assume it is a more common species. Indicators of BLO infection include CNS symptoms out of proportion to the other systemic symptoms of chronic Lyme. There seems to be an increased irritability to the CNS, with agitation, anxiety, insomnia, and even seizures, in addition to other unusually strong symptoms of encephalitis, such as cognitive deficits and confusion. Other key symptoms may include gastritis, lower abdominal pain (mesenteric adenitis), sore soles, especially in the AM, tender subcutaneous nodules along the extremities, and red rashes. These rashes may have the appearance of red streaks like stretch marks that do not follow skin planes, spider veins, or red papular eruptions. Lymph nodes may be enlarged and the throat can be sore. Because standard Bartonella testing, either by serology or PCR, may not pick up this BLO, the blood test is very insensitive. Therefore, the diagnosis is a clinical one, based on the above points. Also, suspect infection with BLO in extensively treated Lyme patients who still are encephalitic, and who never had been treated with a significant course of specific treatment. The drug of choice to treat BLO is levofloxacin. Levofloxacin is usually never used for Lyme or Babesia, so many patients who have tick-borne diseases, and who have been treated for them but remain ill, may in fact be infected with BLO. Treatment consist of 500 mg daily (may be adjusted based on body weight) for at least one month. Treat for three months or longer in the more ill patient. It has been suggested that levofloxacin may be more effective in treating this infection if a proton pump inhibitor is added in standard doses. Another subtlety is that certain antibiotic combinations seem to inhibit the action of levofloxacin, while others seem to be neutral. I advise against using an erythromycin-like drug, as clinically such patients do poorly. On the other hand, combinations with cephalosporins, penicillins and tetracyclines are okay. Alternatives to levofloxacin include rifampin, gentamicin and possibly streptomycin. A very recent article suggests that prior use of quinine-like drugs including atovaquone (Mepron, Malarone) may render Levaquin less effective. Therefore, in a co-infected patient, treat the BLO before you address Babesia species. Levofloxacin is generally well tolerated, with almost no stomach upset. Very rarely, it can cause confusion- this is temporary (clears in a few days) and may be relieved by lowering the dose. There is, however, one side effect that would require it to be stopped- it may cause a painful tendonitis, usually of the largest tendons. If this happens, then the levofloxacin must be stopped or tendon rupture may occur. It has been suggested that loading the patient with magnesium may prevent this problem, and if the tendons do become affected, parenteral high dose vitamin C (plus parenteral magnesium) may afford rapid relief. Unfortunately, levofloxacin and drugs in this family cannot be given to those under the age of 18, so other alternatives, such as azithromycin, are used in children. Incidentally, animal studies show that Bartonella may be transmitted across the placenta. No human studies have been done DISCLAIMER: The Information contained in this monograph is meant for informational purposes only. The management of tick-borne illness in any given patient must be approached on an individual basis using the practitioner’s best judgment.