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Erythema Migrans - Its Diagnosis and Treatment

From a dermatological viewpoint this illness is very poorly identified in Australian General Practice. I have to admit I was one of those before 1992.

Forget the classic bulls eye - if you see one of those good luck to you. Borrelia infection following a tick bite is slow to develop, usually taking some 48 hours to produce erythema. Bear in mind your patient probably hasn't noticed it in this time if in less obvious places. Here's a picture - click here.

Unfortunately a large majority of bite reactions are described as ALLERGY in Australia. This is rather woeful. An urticarial rash of any description must be gone completely in 24 hours. Even if another forms. That is the fundamental definition of acute urticaria. Now your patient might have a local toxic reaction as in most insect bites, or even a small round induration suggesting trivial infection, BUT it is not allergy.

NOW if the lesion around the bite is more than 2cm and persistent more than 2 days then in our country it is either

BORRELIA INFECTION    or    

QUEENSLAND TICK TYPHUS    

And definitely not ALLERGY. 

Please review the brief case history below, presented at Cardiff University in 2004 regarding the distinction. This man tested positive for Borrelia Burgdefori by nested PCR in mid 2009. 

Induration is also a marked feature and if you remember the early phase of a BCG reaction then it is hard like that.

Removal of a tick within 4 hours is believed to prevent infection with Borrelia or other associated tick born illnesses.

Safest course of action is to prescribe the correct antibiotic immediately at presentation no matter how long after a tick bite. The case history reviews the use of tissue PCR but also recently I have found sampling the bite site after removal of the tick can return a positive PCR to Borrelia viz - click here

Treatment protocol (ILADS 2008)

For tick bite

Adults 
The standard is 200mg doxycycline for 28days, alternatively amoxil 1gm tds for 28 days
Children 
Amoxycillin at standard dose for age 28 days
In pregnancy use erythromycin 500mg qid for 28days

For Erythema migrans 

Treat until the eruption is gone plus 6 weeks therapy. Guidelines recommend 200 mg doxycycline but I recommend 400mg.

 

The Case History

Case History - Erythema Migrans                Word count 1198 Presented October 2004  

Introduction

 

D....  is an 84 year old male who presented recently with a tick bite just over 24 hours old.  This is a typical GP practice in a small rural community on the north coast of New South Wales. Tick bites are a perennial problem. Prompt attention and early intervention can prevent considerable morbidity or even fatality. The secondary sequelae of tick bites often cause diagnostic difficulty and in Australia there is also contention about Lyme disease. Repeated serological research has failed to provide satisfactory proof of Burgdorferi spirochaete infection in this country using both European and Northern American antibodies. (1,2) This case and the contention has been the trigger for this report which addresses associated problems of tick bite in  this community.

 

Non-removal of the tick head

Can cause tick paralysis, which appears to be caused by a toxin in the tick saliva (1).  Initial symptoms include unsteady gait, weakness of the limbs, multiple rash, headache, fever, flu symptoms, tender lymph nodes, and partial facial paralysis. Paralysis and death by respiratory failure can occur. Children are at greatest risk.

These scenarios may follow successful removal of the head of the tick

 

Development of acute allergic reaction to the tick (within hours of bite)

 

Rickettsial infection. Northern NSW and Queensland have endemic QTT (Queensland tick typhus). QTT may cause a short-term self-limiting rickettsial illness. Rarely it can cause severe systemic disease. Local signs show after 2 days.
This is NOT the patient:

 

Erythema Migrans and subsequent Lyme disease (described below). Lyme disease is a tick-borne zoonosis caused by the spirochaete bacterium, Borrelia burgdorferi. In this community there are two ticks (1) causing most human infestation – Ixodes Holocyclus (commonly called seed or grass tick at larval stage and bush or shellback at later stages) and Ixodes Comuatus. The former is the causative agent in tick paralysis, the rickettsiae and presumed Lyme disease.

 

Presentation of the case

 

D....  presented with an “itch” in the right cubital fossa.

 

Features

24 hours old

He applied betadine

No history of tick bite reactions.

 

Examination

Live tick

Head buried

Surrounding 1 cm diameter mild erythema

Afebrile and clinically well

 

Action

Immediate removal using forceps - deep in wound

 

 

 

Appropriate clinical care after removal depends upon timing

 

Cleanse site and observe over 30 days for local or systemic reactions – appropriate if short duration and minimal local erythema
Where there is a 1 to 2 cm nodular local reaction at 2 or more days commence doxycycline suspecting tick typhus, after appropriate serological sampling
Where there is a large immediate erythematous area, developed in hours and there is a past history of tick bite allergy commence anti allergic treatment. Such reactions will settle within a few days (1)
If there is a 5cm or more local reaction between 3 and 30 days (1,3) suspect Erythema Migrans with Borrelia burgdorferi infection and commence treatment with

doxycycline 100mg bd for 3 weeks or

amoxicillin for younger children or where the former can not be used

 

D....  was instructed to return if any local inflammation developed or if he felt unwell in anyway.

 

He returned 48 hours later with

Swelling and rash that first erupted in the middle of the night
Localised pain on the radial aspect of the area
Large erythematous rash now measuring 8 cm across and 10 cm long
Intense induration on the radial side measuring 2 by 4 cm. It had the shape of an arc of a circle, the centre of which was the puncture site.

 

 

 

 

The lesion had the clinical appearances of early erythema migrans EM. Serology at this early point for Lyme disease would be negative. At this juncture it was not known by the author that a skin biopsy at the outer edge of induration would be helpful in proving the assumed diagnosis.

 

Treatment was commenced with doxycycline 100 mg bd for 3 weeks. He was reviewed 5 days later and showed excellent response.

 

Discussion and conclusion

 

QTT responds well to tetracyclines but also chloramphenicol

 

Lyme Disease has 3 clinical phases (1)

 

1.      Manifestations include fever, fatigue, headaches, myalgia, arthralgia and lymphadenopathy, usually within 2-3 weeks of infection. Erythema migrans (EM) appears 3-30 days after the bite of an infected tick, usually at the site of inoculation. The initial lesion is a red maculo-papular lesion greater than 5cm in diameter, rarely painful and expands and may reach more than 50cm in diameter, with central clearing and a well-defined, circinate border ("bulls-eye").

 

2.      Symptoms are non-specific and occur weeks or months after the tick bite: carditis, chronic meningitis, mononeuritis (eg Bell's palsy) and conjunctivitis, arthralgia and myalgia.

 

3.      Symptoms occur months or years after exposure. The most typical feature in North American is an erosive arthritis of large joints, particularly the knees. In European patients a chronic skin manifestation, acrodermatitis chronica atrophicans (ACA) occurs.

Isolation of the causative organism from a punch biopsy taken at the edge of the EM lesion is successful in up to 80% of cases but it may be up to 8 weeks before spirochaetes can be detected. Polymerase chain reaction (PCR) has the advantage of greater sensitivity and speed (result in 24 hours). (1) Isolation and/or PCR should be attempted upon presentation of a patient with an EM lesion. (1)

Serology in phase 2 and 3 can be positive and includes (1)

·        Indirect fluorescence antibody test (IFAT)

·        Enzyme linked immunosorbent assay (ELISA)

·        Western immunoblot (WB).

False positive results occur due to cross reactions with other bacteria,viruses and  autoimmune diseases. At the Sixth International Congress on Lyme Borreliosis a standardised interpretation of WB results was accepted. An IgG immunoblot is considered positive if 5 of the following 10 bands are present: 18, 21, 28, 30, 39, 41, 45, 58, 66 and 93kDa. Patients with late stage disease will show 10 or more bands on a WB. (1)

In this community any reaction to a tick bite after 48 hours, if the tick has been removed, is likely to be QTT or possibly Borrelia burgdorferi infection

Such conditions are best treated with doxycycline at this time to prevent latent clinical disease. Amoxicillin may be used in younger children if erythema migrans has occurred but will not be helpful for QTT

The current status of Lyme disease in xxxxxxxxxxxxx see below at references. (1) Until this issue is resolved suspicion is required treating tick bite and where the clinical evidence justifies, appropriate therapy is required

We have found that in this community the clinical condition of erythema migrans can be judged by size and attempts to prove the causative organism Borrelia burgdorferi by skin biopsy should be undertaken. A concerted effort by Australian practitioners in this regard will help towards the task of demystifying Lyme disease in this country.

Attempts to treat a minor localised erythema of less than 48 hours duration can mask the development of more serious sequelae (3)

Treatment interval needs to be updated. Current northern hemisphere opinion for EM has been 2-3 weeks (3). Warmser et al (4) found no difference in follow up after 10 or 20 days doxycycline at 100mg bd in a double blind crossover randomised trial

 

References

 

  1. http://medent.usyd.edu.au/fact/lyme%20disease.htm (The Department of Medical Entomology Sydney University)
    there is a segment now removed and replaced by xxxxxxx because as at January 2011 it was giving rise to misleading search results on Google suggesting Lyme remains a mystery here. There is no mystery now. The x’s replace the following words at the time in 2005 “Australia is that it remains an unproven entity”

2.      Dickeson, D. and Gilbert, G.L. (1994). Lyme Disease in Australia? Western immunoblots not the final answer. Annual Scientific Meeting Australian Society of Microbiology, A125.

3.      Wormser GP, Nadelman RB, Dattwyler RJ, Dennis DT, Shapiro ED, Steere AC, et al. Practice guidelines for the treatment of Lyme disease.                   The Infectious Diseases Society of America. [PMID: 10982743] Clin Infect Dis. 2000;31(suppl 1):1-14

4.      Warmser Ramathan et al. Duration of antibiotic therapy for early Lyme disease – a randomised double blind trial placebo controlled trial.               Ann Intern Med 2003: 138:697-704. 6 may 2003

Further suggested reading Lyme disease in Australia

DOGGETT, S.L., RUSSELL, R.C., Munro, R., Dickeson, D., Ellis, J. Avery, D., Hunt, C.L., Simmonds, J. and Trivett, N. (1994). Lyme disease - the search for the causative agent in southeastern Australia. Arbovirus Research in Australia. Arbovirus Research in Australia, 6: 313-315.

Hudson, B.J., Barry, R.D., Shafren, D.R., Wills, M.C., Caves, S.F. and Lennox, V.A. (1994). Does Lyme borreliosis exist in Australia? Journal of Spirochaetal and Tick-Borne Disease; 1: 46-51.

Piesman, J. and Stone B.F. (1991). Vector competence of the Australian paralysis tick, Ixodes holocyclus, for the Lyme disease spirochaete Borrelia burgdorferi. International Journal Parasitology, 21: 109-11.

RUSSELL, R.C., DOGGETT, S.L., Munro, R., Ellis, J., Avery, D., Hunt, C., and Dickeson, D. (1994). Lyme disease: A search for a causative agent in ticks in southeastern Australia. Epidemiology and Infection, 112: 375-384.

RUSSELL, R.C. (1995). ?Lyme disease in Australia - still to be proven! Emerging Infectious Diseases, 1: 29-31.

Wills, M.C. and Barry, R.D. (1991). Detecting the cause of Lyme disease in Australia [letter]. Medical Journal of Australia, 155: 275.