Successful treatment of erythema migrans Afzelius
Hollström E. Acta Derm Venereol Suppl (Stockh) 1951;31:235-243  
51_01 Successful tx EM.tif  

An account is given of sixteen cases of erythema chronicum migrans Afzelius treated with bismuth, neoarsphenamine, mapharside, and penicillin, either separate or in various combinations. In 14 cases (two patients defaulted) the therapeutical action upon the erythema was unmistakable and sometimes very rapid. If the dosage was insufficient, or if there were long intervals between the injections, the erythema was apt to pale down only partly or disappear temporarily. Penicillin appeared somewhat superior to the other drugs used, entailing a highly gratifying curative effect in a case with frank meningitis. The aetiology is discussed of the condition, special attention being given to the conclusions possibly to be drawn from the good therapeutical results.   "An efficacious method of treating erythema chronicum migrans has not been known formerly, nor was it considered strictly necessary to treat that condition as causing but mild discomfort. Since, however, erythema migrans has been shown in a proportion of instances to involve the central and peripheral nervous system (Hellerström, 1930; Bode, 1933; Bing, 1945; Gelbjerg-Hansen, 1945; Sälde, 1946; Dalsgaard-Nielsen and Kierkegaard, 1947; Leczinsky, 1949),1 at the present moment the question of successful treatment is of current interest even from the practical point of view. On the other hand, the aetiology of the condition being obscure, apart from the established fact that in the major proportion of instances the eruption follows upon a tick bite, it has hitherto not been possible to attack the causal factor.
Using the spirochaetal stain envolved by him, Lennhoff has succeeded in demonstrating organisms resembling spirochaetes in biopsy specimens taken from the erythematous lesions. With a view to the possibility of the spirochaetes demonstrated being the causal factor, according to Lennhoff's directions groups of erythema migrans cases have been treated with spirochaeticides at the St. Göran's Hospital, Karolinska Sjukhuset, and Stockholm South Hospital. The series comprises 16 patients with typical erythema chronicum migrans."
Patients received the following treatment:
1: Tickbite no. EM 3 mo; iodobismol; eruption disappeared in a week
2: Tickbite no. EM 3 mo; wait 3 mo expanding; bismuth subsalicylate; disappeared in a week
3: Tickbite yes. EM 6 mo. Biopsy, Lennhoff saw spirochaetes. Bismuth subsalicylate x16 + Neoarspenamine x 7 over a period of 6 mo, EM faded and recurred
4: Tickbite no. EM; bismuth subsalicylate x3; EM disappeared in >14 days
5: Tickbite no. EM.; iodobismol x8 EM disappeared, recurred?.. iodobismol + neoarspenamine x 4
6: Tickbite no. EM; iodobismol x 2 EM unchanged. Defaulter.
7: Tickbite yes. EM. iodobismol x2 EM disapperared, recurred. .. bismuth subsalicylate .. Mapharside .. Neoarsphenamine several times over a period of 6 mo. EM not fully gone.
8: Tickbite yes. EM. Iodobismol x2, EM unchanged, patient denies further treatment
9: Tickbite yes. EM. penicillin ointment, penicillin 450000 x2, subjective signs subsided.
10: Tickbite yes. EM. Iodobismol x6 EM disappear, but stinging
11: Tickbite yes. EM. In a couple of mo. Multiple EM's. Meningitis. Neoarspenamine .. Maphars .. Still EM penicillin ointment .. Penicillin 300000, EM disappeared.
12: Tickbite yes. Multiple Dis EM. Headache, procain penicillin 300000 x2, headache disappered after the first, EM after the second.
13: Tickbite no, but cutting timber. Headache, EM Bäfverstedt made a diagnosis of EM w mingitis; at 3 hour intervals in increasing doses 30000, 60000, 75000, 100000, striking subjective improvement within 2 days .. Ct. Penicillin 100000 x6 until a total of 10000000. EM and nervous symptoms disappered.
14: Tickbite yes. EM. Penicillin ointment 450000 x 2. EM disapperared in 2 weeks.
15: Tickbite yes. EM. WR-, SR 30, eosinophilia 6%. Material taken from the erythematous border was ground in a mortar and injected intradermally into two subjects without evoking EM (obs 4 mo). Procain penicillin x 4. EM disappeared within a couple of weeks.
16: Tickbite no. EM. Weak arm. Spinal meningitis. Penicillin 450000 x5 EM disappeared, force normal.
8/16 had tickbite. 2 had 2-3 EM. The rest 1 EM.
On CSF exam. 5 (11,12,13,15,16); 3 had meningitis. In case 11 no nervous symptoms despite meningitis. One patient without meningitis had for about a month been inconvenienced by headache.
Considerable side effects of non antibiotic drug leading to non-compliance.
6 cases treated with penicillin alone from 600000-10000000 u.
1 became asymptomatic in 2 mo.
4 became asymptomatic in 3 weeks, whereas 1 had a coin-sized remnant.
"Of particular interest is the action of penicillin on the neuro-meningeal symptoms sometimes associated with erythema migrans."
"The therapeutical results achieved with penicillin indicate that erythema migrans is infectious in nature, and the effects of all the drugs used in treatment, in particular the bismuth salts and neoarsphenamine, tend to suggest a spirochaetae as the causative organism. Definite evidence is still lacking in this respect, but the therapeutical results in conjunction with Lennhoff's findings of spirochaetes in histological sections prepared from lesions of erythema migrans and with the demonstrated presence of spirochaetes in ticks, render probable that a spirochaete is the infective agent."