CAMEO
' .
• :
ROSEOLAR LESIONS IN LYME DISEASE: ISOLATION OF THE CAUSATIVE AGENT GIUSTO TREVISAN, M.D., MARINA CINCO, M.Sc, AND ANTONINA AGOLZER, M.D.
A 42-year-old man came to us for the first time in May 1990. In the spring of 1988, during an excursion in tbe mountains, he had been bitten by a tick on the lateral pretibial region of the right leg. Some weeks later, the patient noticed the onset of a progressive annular erythema, which expanded from the bite site to the whole right leg. No therapy was received.
pattern was the same as that of the BITS strain, the first Borrelia tick isolated in the same territory. These findings indicate that the new Borrelia strain, isolated from human skin for the first time in Italy, belongs to the species S. burgdorferi and shares the antigenic pattern which is the most common among European 6. burgdorferi strains. The patient had 14-days therapy with josamycin at a dose of 2 g per day orally. The skin lesions rapidly disappeared while myalgia and paraesthesia disappeared during the following 2 months.^
The skin lesion did not disappear, and 1 year later, in October 1989, the indirect immunofluorescence test was performed, after Treponema phagedenis absorption (IFI/ Abs), to identify anti-Sorre//a burgdorferi antibodies. The test was positive for IgG at 1:256. Ceftriaxone sodium, 2 g/ day intramuscular, was then administered to the patient for 2 weeks. The subsequent serologic test (November 1989) gave a titer of 1:64 for IgG. The patient came to us 7 months later, in May 1990. In the previous weeks, several roseolar lesions had appeared on his trunk and limbs. The largest lesion (3x2 cm) was located on the right suprarotular region (Fig. 1). Smaller lesions were present on the right hypochondrium and on the left forearm. The patient suffered from right leg myalgia and paraesthesia, as well as from asthenia (which had exacerbated in the previous weeks). There was no lymphadenopathy. Tests were performed to detect B. burgdorferi serum antibodies and to isolate the etiologic agent from the affected skin. The results were the following: IFI/Abs test, 1:32 for IgG, negative for IgM; ELISA test, positive for IgG, negative for IgM. Isolation of the etiologic agent was carried out by inoculating a punch biopsy (6 mm) from the suprarotular skin lesion in BSK medium.^ After 16 days of incubation at 34°C, dark-field microscopy observations revealed the presence of spirochetes, which were very similar to B. burgdorferi in shape and motility. The isolated strain, named DA, was analyzed by SDS-PAGE and Western Blotting with monoclonal antibodies (MABS) directed against the main antigens of the species B. burgdorferi (gift from A. Barbour, University of S. Antonio, Texas).^
Figure 1.
Suprarotular skin lesion from which the DA strain
ol Borrelia burgdorferi has been isolated.
KD
The isolated strain was S. burgdorferi, because it shared the same electrophoretic pattern as the reference strain B31 (Fig. 2) and in addition, it reacted with MABS H9724 and H5332, which are directed against the 41 kd flagellin and the OspA protein. On the other hand, no reactivity was found with MABS H3TS and H6831, which are directed against the second epitope of OspA and OspB proteins. This behavior
•4 42
25
412.5
From the Department of Dermatology and the Institute of Microbiology, University of Trieste, Trieste, Italy.
BITS
Address for correspondence; Giusto Trevisan, M.D., University of Trieste, Department of Dermatology, Cattinara Hospital, 34100 Trieste, Italy.
DA
B31
Figure 2. SDS-PAGE stained with Coomassie blue Borrelia strains BITS (lane 1), DA (lane 2), and B31 (lane 3). Mass markers on the right.
507
Internarional journal of Dernunoiogy Vol. 31, No. 7, July 1992
• The isolation of B. burgdorferi from the affected skin in our case confirms diagnosis of Lyme disease and excludes the possibility that the ceftriaxone sodium treatment may have induced a Jarisch-Herxheimer skin reaction. It is still to be explained why ceftriaxone sodium was ineffective in vivo, while effective in vitro on the same isolated strain. Perhaps the drug did not reach the bacterium in the tissues, or the organism in the tissues may acquire the capability to resist the abovementioned antibiotic. The ineffectiveness of ceftriaxone sodium in our case is in contrast with observations made by other authors^"** who reported its effectiveness in Lyme disease.
Figure 3. Roseolic patch on the trunk (arrows).
REFERENCES
DISCUSSION
1.
Erythema chronicum migrans (ECM) is the hallmark of early Lyme disease (LD)."* Multiple annular lesions., small in size, are relatively frequent and generally appear in the early stage of LD.' Our patient did not have annular lesions, and moreover, his lesions had developed 1.5 years after the onset of ECM (late secondary stage). Our data seems to differ from those reported by Burke et al.;*" they noted that in their case, the lesions were numerous and had developed at an earlier stage. On the other hand, the fact that Lt) secondary manifestations present a lower number of lesions in case of a delayed eruption reminds us of the evolution of secondary syphilodermata (Fig. 3). This observation emphasizes that the etiologic agent of Lyme borreliosis can be isolated in the skin in all three stages of the disease; in the early stage (erythema chronicum migrans), in the third stage (acrodermatitis chronica atrophicans), and in the secondary one, as described here.
Smoking and the Skin
2.
3.
4. 5. 6.
7.
8.
•
Barbour A. Isolation and cultivation of Lyme disease spirochetes. Yale J Biol Med 1984; 57:521-525. Cinco M, Banfi E, Trevisan G, Stanek G. Gharacterization of the first tick isolate of "Borrelia burgdorferi" from Italy. APMIS 1989; 97:381-382. Trevisan G, Ginco M. Efficacy of iosamycin in Lyme borreliosis treatment. J Ghemoter 1991; 4 (suppl.):451452. Scrimenti RJ. Erithema chronicum migrans. Arch Dermatol 1970;' 102:104-105. Trevisan G, Ginco M. Lyme disease: a general survey. Int J Dermatol 1990; 29:1-8. Burke WA, Steinbaugh JR, O'Keefe EJ. Lyme disease mimicking secondary syphilis. J Am Acad Dermatol 1986; 14:137-139. Dattwyler RJ, Halperin JJ, Pass H, Luft BJ. Geftriaxone as effective therapy in refractory Lyme disease. J Infect Dis 1987; 15:1322-1325. Dattwyler RJ, Halperin JJ, Volkmann DJ, Luft BJ. Treatment of late Lyme borreliosis-randomised comparison of ceftriaxone and penicillin. Lancet 1988; i:l 191-1194.
,
Smoking of cigarettes is a known risk factor for the development of pulmonary and arterial disorders. The effects of cigarette smoking on the skin has received little attention, although it was suggested as early as 1856 by Solly, who described the pale sallow skin colour and more pronounced wrinkles on the faces of smokers. Later, a highly significant statistical relationship was shown between wrinkling of the skin on the face and smoking. From Frances C, Boisnic S,
Fiartmann DJ, et al. Changes in the elastic tissue of the non-sun-exposed skin of cigarette smokers. Br J Dermatol 1991; 125:43-47. 508
' .
• :
ROSEOLAR LESIONS IN LYME DISEASE: ISOLATION OF THE CAUSATIVE AGENT GIUSTO TREVISAN, M.D., MARINA CINCO, M.Sc, AND ANTONINA AGOLZER, M.D.
A 42-year-old man came to us for the first time in May 1990. In the spring of 1988, during an excursion in tbe mountains, he had been bitten by a tick on the lateral pretibial region of the right leg. Some weeks later, the patient noticed the onset of a progressive annular erythema, which expanded from the bite site to the whole right leg. No therapy was received.
pattern was the same as that of the BITS strain, the first Borrelia tick isolated in the same territory. These findings indicate that the new Borrelia strain, isolated from human skin for the first time in Italy, belongs to the species S. burgdorferi and shares the antigenic pattern which is the most common among European 6. burgdorferi strains. The patient had 14-days therapy with josamycin at a dose of 2 g per day orally. The skin lesions rapidly disappeared while myalgia and paraesthesia disappeared during the following 2 months.^
The skin lesion did not disappear, and 1 year later, in October 1989, the indirect immunofluorescence test was performed, after Treponema phagedenis absorption (IFI/ Abs), to identify anti-Sorre//a burgdorferi antibodies. The test was positive for IgG at 1:256. Ceftriaxone sodium, 2 g/ day intramuscular, was then administered to the patient for 2 weeks. The subsequent serologic test (November 1989) gave a titer of 1:64 for IgG. The patient came to us 7 months later, in May 1990. In the previous weeks, several roseolar lesions had appeared on his trunk and limbs. The largest lesion (3x2 cm) was located on the right suprarotular region (Fig. 1). Smaller lesions were present on the right hypochondrium and on the left forearm. The patient suffered from right leg myalgia and paraesthesia, as well as from asthenia (which had exacerbated in the previous weeks). There was no lymphadenopathy. Tests were performed to detect B. burgdorferi serum antibodies and to isolate the etiologic agent from the affected skin. The results were the following: IFI/Abs test, 1:32 for IgG, negative for IgM; ELISA test, positive for IgG, negative for IgM. Isolation of the etiologic agent was carried out by inoculating a punch biopsy (6 mm) from the suprarotular skin lesion in BSK medium.^ After 16 days of incubation at 34°C, dark-field microscopy observations revealed the presence of spirochetes, which were very similar to B. burgdorferi in shape and motility. The isolated strain, named DA, was analyzed by SDS-PAGE and Western Blotting with monoclonal antibodies (MABS) directed against the main antigens of the species B. burgdorferi (gift from A. Barbour, University of S. Antonio, Texas).^
Figure 1.
Suprarotular skin lesion from which the DA strain
ol Borrelia burgdorferi has been isolated.
KD
The isolated strain was S. burgdorferi, because it shared the same electrophoretic pattern as the reference strain B31 (Fig. 2) and in addition, it reacted with MABS H9724 and H5332, which are directed against the 41 kd flagellin and the OspA protein. On the other hand, no reactivity was found with MABS H3TS and H6831, which are directed against the second epitope of OspA and OspB proteins. This behavior
•4 42
25
412.5
From the Department of Dermatology and the Institute of Microbiology, University of Trieste, Trieste, Italy.
BITS
Address for correspondence; Giusto Trevisan, M.D., University of Trieste, Department of Dermatology, Cattinara Hospital, 34100 Trieste, Italy.
DA
B31
Figure 2. SDS-PAGE stained with Coomassie blue Borrelia strains BITS (lane 1), DA (lane 2), and B31 (lane 3). Mass markers on the right.
507
Internarional journal of Dernunoiogy Vol. 31, No. 7, July 1992
• The isolation of B. burgdorferi from the affected skin in our case confirms diagnosis of Lyme disease and excludes the possibility that the ceftriaxone sodium treatment may have induced a Jarisch-Herxheimer skin reaction. It is still to be explained why ceftriaxone sodium was ineffective in vivo, while effective in vitro on the same isolated strain. Perhaps the drug did not reach the bacterium in the tissues, or the organism in the tissues may acquire the capability to resist the abovementioned antibiotic. The ineffectiveness of ceftriaxone sodium in our case is in contrast with observations made by other authors^"** who reported its effectiveness in Lyme disease.
Figure 3. Roseolic patch on the trunk (arrows).
REFERENCES
DISCUSSION
1.
Erythema chronicum migrans (ECM) is the hallmark of early Lyme disease (LD)."* Multiple annular lesions., small in size, are relatively frequent and generally appear in the early stage of LD.' Our patient did not have annular lesions, and moreover, his lesions had developed 1.5 years after the onset of ECM (late secondary stage). Our data seems to differ from those reported by Burke et al.;*" they noted that in their case, the lesions were numerous and had developed at an earlier stage. On the other hand, the fact that Lt) secondary manifestations present a lower number of lesions in case of a delayed eruption reminds us of the evolution of secondary syphilodermata (Fig. 3). This observation emphasizes that the etiologic agent of Lyme borreliosis can be isolated in the skin in all three stages of the disease; in the early stage (erythema chronicum migrans), in the third stage (acrodermatitis chronica atrophicans), and in the secondary one, as described here.
Smoking and the Skin
2.
3.
4. 5. 6.
7.
8.
•
Barbour A. Isolation and cultivation of Lyme disease spirochetes. Yale J Biol Med 1984; 57:521-525. Cinco M, Banfi E, Trevisan G, Stanek G. Gharacterization of the first tick isolate of "Borrelia burgdorferi" from Italy. APMIS 1989; 97:381-382. Trevisan G, Ginco M. Efficacy of iosamycin in Lyme borreliosis treatment. J Ghemoter 1991; 4 (suppl.):451452. Scrimenti RJ. Erithema chronicum migrans. Arch Dermatol 1970;' 102:104-105. Trevisan G, Ginco M. Lyme disease: a general survey. Int J Dermatol 1990; 29:1-8. Burke WA, Steinbaugh JR, O'Keefe EJ. Lyme disease mimicking secondary syphilis. J Am Acad Dermatol 1986; 14:137-139. Dattwyler RJ, Halperin JJ, Pass H, Luft BJ. Geftriaxone as effective therapy in refractory Lyme disease. J Infect Dis 1987; 15:1322-1325. Dattwyler RJ, Halperin JJ, Volkmann DJ, Luft BJ. Treatment of late Lyme borreliosis-randomised comparison of ceftriaxone and penicillin. Lancet 1988; i:l 191-1194.
,
Smoking of cigarettes is a known risk factor for the development of pulmonary and arterial disorders. The effects of cigarette smoking on the skin has received little attention, although it was suggested as early as 1856 by Solly, who described the pale sallow skin colour and more pronounced wrinkles on the faces of smokers. Later, a highly significant statistical relationship was shown between wrinkling of the skin on the face and smoking. From Frances C, Boisnic S,
Fiartmann DJ, et al. Changes in the elastic tissue of the non-sun-exposed skin of cigarette smokers. Br J Dermatol 1991; 125:43-47. 508
