The Best Treatment for Lyme Disease for Children

I recently posted about my son’s sudden knee effusion. https://drcremers.com/2017/05/sterile-knee-effusion.html

A covering MD for his usual pediatrician saw him 5 days ago. This doctor seemed a bit lost of what to order so I asked for a Rheumatoid factor and Lyme titer, CBC, ESR, CRP.  I must confess I drew the blood as their phlebotomist was late and my son was very upset at the idea of being late to school. Given the choice of waiting 15 minutes for the phlebotomist or having mom draw the blood, he reluctantly chose mom: ugh.

The following day, I called the covering MD who saw him to request a Doxycycline Rx just in case it was positive, as it takes days for the Lyme titer to come back . This doctor became very annoyed as if to say, “who are you to tell me what to prescribe.” That was not fun.

My son got much worse and yesterday we had to take him to the ER as he could not walk and was very upset and having more pain. Wonderful Dr. Theiss at Inova Children’s ER took incredible care of John. I love Dr. Theiss! He took very good care of my son and did a tap of the knee: withdrew 50cc of fluid and called me immediately with the results. It was not an infected or septic joint but I should see Rheumatology.

I just called his Pediatrician’s office. The Lyme Western Blot is Positive for Lyme.

Moral to the story: if your child has a swollen joint and  you live in any location where there is LYME disease, treat with Doxycycline 2mg/kg/ day (maximum for kids is 100mg po bid) until the Lyme titer comes back. If it is positive, continue Doxycycline 100mg po bid for 28 days (at least: assuming no neurological signs develop: I pray my son does not have any

Controversy exists on how best to treat Lyme.

Here is the research so far.

Lyme disease is due to a bacteria Borrelia burgdorferi causes Lyme disease.Deer ticks can carry this bacterium. When a person gets bitten by a deer tick it can transfer the bacteria to your body, which is a total bummer!


The patient may experience symptoms in the 
1. joints: any swollen knee in a child in a Lyme disease area needs a Lyme test & start treatment until Lyme titers come back. 
2. skin: bullseye rash is classic.  
3. muscles, 
4. nervous system (peripheral nerves (nerves outside the brain and spinal cord), the brain, and the spinal cord). 


Without antibiotic treatment, neurological Lyme disease either may resolve or cause long-term problems. 


Neurological Lyme disease differs between Europe and the United States, probably because of differences in B. burgdorferi between the continents. 


Limited information exists about which antibiotics are better for the treatment of neurological Lyme disease which is frustrating.




Lyme neuroborreliosis (LNB) is a group of many diseases that can affect the central nervous system (CNS) and the peripheral nervous system (PNS), or both, as a result of infection with or the postinfectious consequences of different species of the spirochete bacterium Borrelia burgdorferi. 


These organisms are transmitted by particular Deer Ticks called Ixodid ticks. They are endemic areas in the United States and Europe. Although a multitude of clinical manifestations of LNB have been reported, the most common are:
1. radicular pains, 
2. facial paralysis, and 
3. meningitis, referred to as Bannwarth’s syndrome in Europe (Bannwarth 1941; Bannwarth 1944). It was not until 1981 that entomologist Willy Burgdorfer and colleagues in the USA suspected that the cause of Lyme disease was a tick-borne spirochete (Burgdorfer 1982). 


LNB is one of the most common and important complications of Lyme disease. The diagnosis of LNB requires confirmation of infection with B. burgdorferi plus evidence of involvement of the CNS, the PNS, or both. According to the Centers for Disease Control and Prevention, from the 154,405 cases of Lyme disease reported during 2001 to 2010 in the United States, 14% were identified with facial palsy, radiculoneuropathy, meningitis, or encephalitis (CDC 2011a). 


5% of individuals with an untreated erythema migrans will develop LNB (Hansen 2013): so get treated fast!


For LNB and Brain involvement of Lyme:
In Ljostad 2008, investigators obtained CSF at inclusion and at 13 days and 4 months after the start of antibiotic treatment. No significant difference was found between oral doxycycline and intravenous ceftriaxone for reduction in CSF cell count at 13 days (P = 0.89) or 4 months (P = 0.56) after the start of treatment (data not provided; low-quality evidence).




The safety population included 113 participants with available data. The RR of adverse event between the two groups favored doxycycline, but the data were very imprecise and allowed for the possibility of no difference (RR 0.79, 95% CI 0.51 to 1.23; N = 113; moderate-quality evidence; Analysis 2.3). Three participants discontinued ceftriaxone treatment due to adverse events: one with cholecystitis, one with stomatitis and proctitis, and one with allergy. There were no other serious adverse events. There was one serious adverse event but no withdrawals in the doxycycline group. Results for adverse events leading to discontinuation (RR 0.14, 95% CI 0.01 to 2.71; N = 118; Analysis 2.4) and serious adverse events (RR 0.33, 95% CI 0.04 to 3.05; N = 113; Analysis 2.5) also favored doxycycline but with serious imprecision. Diarrhea, nausea, and urticaria were reported for 19, 15, and 3 participants, respectively; all were generally mild. Emergence of new symptoms compatible with LNB or intensification of symptoms during treatment was not reported.


Karlsson 1994 compared a 14-day treatment with penicillin G to 14 days of oral doxycycline in 54 participants with LNB. The study included only participants with objective findings and a positive serology or evidence of abnormal CSF. Investigators used a rating of subjective and objective findings on a Likert scale from 0 to 3 (no symptoms, mild symptoms, moderate or severe symptoms) for primary efficacy. The RRs for improvement and resolution with penicillin G versus oral doxycycline at 12 months were 1.0 (95% CI 0.92 to 1.08) and 0.95 (95% CI 0.77 to 1.18), respectively (N = 51; low-quality evidence; Analysis 3.1; Analysis 3.2). Participants were followed for 12 months, with no difference found between the two treatment arms except for the fact that more participants treated with doxycycline reported vertigo at the end of treatment but not at one month. One participant in each treatment group was retreated because of residual symptoms. Subjective symptoms were completely absent at 12 months except for 1 penicillin G participant with neuromuscular pain and hypoesthesia and 1 doxycycline participant with arthralgia. Selection bias is a concern in this study due to a considerable imbalance in the number of participants randomized to each treatment arm. The report provided few statistics and did not allow a distinction to be made between participant- and physician-based judgements. Objective judgement of findings at the end of follow-up was implied but not well documented, thus this study did not use a well-characterized objective measure of efficacy by a physician.


Kohlhepp 1989 randomized a clinically well-defined cohort of 75 participants with predominantly acute (n = 67) but also chronic (n = 8) LNB to a 10-day course of intravenous doxycycline or intravenous penicillin G. Follow-up was 12 months, but for cases with residual symptoms the follow-up was three years. The primary outcome was the treating physicians’ categorical grading of the clinical status as “no remission,” “partial remission,” or “full remission,” based on objective and subjective signs and symptoms with no specification given. At the end of treatment, over 80% of participants had responded to some degree in both groups. Early responders were usually asymptomatic after six months. Pain, meningitic symptoms, and acute cranial neuritis began to remit within days. A slower improvement was observed in symptoms of radiculitis, myelitis, encephalitis, and peripheral neuropathy. According to data in Figure 2 of the study report, at six months the RR for “partial remission” (improvement) showed no clear difference between interventions (RR 1.10, 95% CI 0.95 to 1.28), whereas the RR for “full remission” (resolution) favored doxycycline, but with the possibility of no effect (RR 1.42, 95% CI 0.83 to 2.42; low-quality evidence; Analysis 4.1 and Analysis 4.2). At 12 months, the RRs for “partial remission” and “full remission” were 0.98, 95% CI 0.80 to 1.21 and 0.96, 95% CI 0.70 to 1.31, respectively (low-quality evidence; Analysis 4.1 and Analysis 4.2). Of the 22 participants with only partial remission after 6 months, 10 chose to receive retreatment with penicillin G, 6 from the penicillin arm and 4 from the doxycycline arm. Three years after randomization, the recovery rate was 94% in the doxycycline and 91% in the penicillin G group if the retreatment group was excluded. In the “partial remission” group, 7/10 participants who chose retreatment recovered completely, compared to 7/12 of those who did not choose retreatment (no significant difference). Participants with partial remission had central nervous system involvement, a disseminated clinical picture, and/or a longer disease duration. The authors concluded that there was no clinically relevant difference between doxycycline and penicillin G. The number of participants with chronic LNB was too low for any subgroup analysis. In addition, the majority of these chronic LNB cases were also treated with immunosuppressants.

In summary:
  1. We found no clinical trials to evaluate the absolute efficacy of initial treatment with antibiotics for LNB. The lack of placebo-controlled studies prevented us from assessing the extent to which antibiotics improve spontaneous recovery from LNB or prevent further complications.
  2. Seven randomized studies mostly at high risk of bias and of marked heterogeneity provided some relative efficacy data for antibiotic treatment of LNB, only one of which was blinded (Ljostad 2008). All studies were from Europe.
  3. Marked heterogeneity among the eligible studies in terms of differences in inclusion and exclusion criteria, supportive laboratory diagnostic criteria, primary and secondary outcome measures, treatment regimens, prior antibiotic treatment, and duration of disease and follow-up prevented incorporation of results into a systematic meta-analysis. The quality of the evidence was mostly low to very low; we have formally presented this in ‘Summary of findings’ tables.
  4. All studies reported improvement in the majority of participants following antibiotic treatment, and the majority had complete resolution of their symptoms in long-term follow-up, irrespective of the antibiotic regimen received and in the case of doxycycline regardless of whether it was given orally or intravenously.
  5. Only three studies provided information on the need for retreatment (Kohlhepp 1989; Karlsson 1994; Ljostad 2008).
  6. Where measured, objective biomarkers of response (CSF pleocytosis) recovered in almost all participants examined at follow-up.
  7. Incomplete or poor treatment responses for the efficacy outcomes used in the trials were reported in only a minority of participants, regardless of the antibiotic used. Where no or partial response was recorded, there were no obvious differences in the rates of partial or lack of response between treatments.
  8. All of the antibiotics studied appear to have been generally well tolerated as judged by all adverse event reporting. Only four studies provided information on discontinuation due to adverse events (Pfister 1989; Mullegger 1991; Pfister 1991; Ljostad 2008), which can have a major impact on the outcome of the treatment.
  9. The single study conducted in children treated very early in their disease reported full remission in all children. This study had a high risk of bias, with qualitative outcomes and incomplete follow-up data.

Implications for practice

For early disseminated (acute or stage II) Lyme neuroborreliosis (LNB), low- to very low-quality evidence suggests that the majority of people with LNB respond to antibiotics with known brain penetration and appropriate activity spectra, namely penicillin G, ceftriaxone, cefotaxime, and doxycycline, either oral or intravenous. There is no accurate estimate of the absolute efficacy of these antibiotics, as there were no appropriate studies from which to infer this. None of the included trials had a placebo control for initial antibiotic treatment, and most had limited power and lacked consistent and well-defined efficacy endpoints, study duration, and entry criteria. Also, the studies employed a range of treatment duration, from 10 to 21 days. All studies were conducted in Europe and none in the United States, thus no direct conclusion can be drawn on the effect of antibiotic treatment for LNB in the United States. The number of participants with late disseminated (chronic or stage III) LNB in the included trials was very low, and no useful separate conclusions can be drawn about its treatment with antibiotics. We observed no evidence of additional efficacy in a trial extending initial ceftriaxone treatment with amoxicillin. No firm conclusions can be drawn on the relative efficacy of the four antibiotics we reviewed. In the majority of cases reported in the seven included studies, European LNB was treatable with antibiotic regimens recommended in national guidelines, with marked improvement from baseline impairment. A minority of people do not improve after initial treatment.
Interventions
14-day course of either:
  • oral doxycycline 200 mg daily (N = 54); or
  • intravenous ceftriaxone 2 g daily (N = 48).
Interventions
14-day course of:
  • intravenous penicillin G (3 g every 6 hours) (N = 23); or
  • oral doxycycline (200 mg once daily) (N = 31)



http://onlinelibrary.wiley.com.ezp.welch.jhmi.edu/doi/10.1002/14651858.CD006978.pub2/full




More info from WebMD: 

A Lyme disease test is done to diagnose Lyme disease in people who have symptoms of Lyme disease. Symptoms may include:
Symptoms of chronic Lyme disease infection include joint pain, stiffness, and problems with the heart, brain, or nerves.
Testing is most accurate when you have risk factors for Lyme disease or symptoms of the disease.
 2016 Dec 8;12:CD006978. doi: 10.1002/14651858.CD006978.pub2.

Antibiotics for the neurological complications of Lyme disease.

Cadavid D1, Auwaerter PG2, Rumbaugh J3, Gelderblom H4.

Abstract

BACKGROUND:

Various central nervous system-penetrant antibiotics are bactericidal in vitro and in vivo against the causative agent of Lyme neuroborreliosis (LNB), Borrelia burgdorferi. These antibiotics are routinely used clinically to treat LNB, but their relative efficacy is not clear.

OBJECTIVES:

To assess the effects of antibiotics for the treatment of LNB.

SEARCH METHODS:

On 25 October 2016 we searched the Cochrane Neuromuscular Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, and Embase. We searched clinical trial registers on 26 October 2016. We reviewed the bibliographies of the randomized trials identified and contacted the authors and known experts in the field to identify additional published or unpublished data. There were no language restrictions when searching for studies.

SELECTION CRITERIA:

Randomized clinical trials of antibiotic treatment of LNB in adults and children that compared any antibiotic treatment, including combinations of treatments, versus any other treatment, placebo, or no treatment. We excluded studies of entities considered as post-Lyme syndrome.

DATA COLLECTION AND ANALYSIS:

We used standard methodological procedures expected by Cochrane.

MAIN RESULTS:

We identified seven randomized studies involving 450 European participants with LNB for inclusion in this systematic review. We found no trials conducted in the United States. Marked heterogeneity among these studies prevented meta-analysis. None of the studies included a placebo control on the initial antibiotic treatment, and only one was blinded. None were delayed-start studies. All were active comparator studies, and most were not adequately powered for non-inferiority comparison. The trials investigated four antibiotics: penicillin G and ceftriaxone in four studies, doxycycline in three studies, and cefotaxime in two studies. One study tested a three-month course of oral amoxicillin versus placebo following initial treatment with intravenous ceftriaxone. One study was limited to children. The trials measured efficacy using heterogeneous physician- or patient-reported outcomes, or both. In some cases cerebrospinal fluid analysis was included as an indirect biomarker of disease and outcome. None of the studies reported on our proposed primary outcome, ‘Improvement in a measure of overall disability in the long term (three or more months).’ None of the trials revealed any between-group differences in symptom resolution in response to active treatment. In general, treatment was tolerated well. The quality of adverse event reporting, however, was low.

AUTHORS’ CONCLUSIONS:

There is mostly low- to very low-quality clinical evidence from a limited number of mostly small, heterogeneous trials with diverse outcome measures, comparing the relative efficacy of central nervous system-penetrant antibiotics for the treatment of LNB. The few existing randomized studies have limited power and lack consistent and well-defined entry criteria and efficacy endpoints. It is not possible to draw firm conclusions on the relative efficacy of accepted antibiotic drug regimens for the treatment of LNB. The majority of people are reported to have good outcomes, and symptoms resolve by 12 months regardless of the antibiotic used. A minority of participants did not improve sufficiently, and some were retreated. These randomized studies provide some evidence that doxycycline, penicillin G, ceftriaxone, and cefotaxime are efficacious in the treatment of European LNB. No evidence of additional efficacy was observed when, in one study, an initial antibiotic treatment with intravenous ceftriaxone was followed by additional longer treatment with oral amoxicillin. There is a lack of evidence identified through our high-quality search strategy on the efficacy of antibiotics for treatment of LNB in the United States.

References:
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