Clinical Investigator
Clin Investig (1992) 70:1073 1078
Case Report
© Springer-Verlag 1992
Erythema nodosum of dental origin W. Kirch 1 and U. Diihrsen 2 I Medizinische Klinik, Christian-Albrechts-UniversitS.t Kiel 2 H Medizinische Klinik, Universit/itskrankenhaus Hamburg, Eppendorf
Summary. The association of erythema nodosum and dental infectious foci has rarely been described in the literature. This report concerns four women who developed erythema nodosum either following dental treatment associated with gingival bleeding or due to infectious dental foci. In these cases, tooth extraction, removal of dental deposits, interrupted pulp treatment, apical periodontitis, or a relicted root were identified as causes of the development of erythema nodosum. Upon admission to the hospital, these patients also presented fever and and a maximally elevated erythrocyte sedimentation rate (ESR). In all instances, surgical treatment of the dental foci and/or administration of antibiotics rapidly led to the regression of the erythema nodosum, as well as to the normalization of body temperature and ESR. The cases described indicate that antecedent dental treatment and the possible presence of infectious dental loci should be considered in the differential diagnosis of erythema nodosum when taking the patient's medical history. This approach may avoid unnecessary, possibly invasive diagnostic procedures and can lead to rapid improvement in the patient's clinical status.
Key words: Erythema nodosum - Dental origin Dental infectious foci
Erythema nodosum is characterized by recurrent, painful, livid, nodular perivascular infiltrates measuring up to 10 x 10 cm which tend to be localized in the cutaneous/subcutaneous tissue, preferentially on the lower extremities. From the etiological point of view, this syndrome has been associated with tuberculosis, sarcoidosis, infectious intestinal diseases, rheumatoid diseases, and drug allergies. Frequently, the origin of an erythema nodosum cannot be ascertained; it is then termed idiopathic erythema nodosum. As streptococcal and staphylococcal (e.g., oropharyngeal) infections have been Abbreviations: ESR = erythrocyte sedimentation rate
implicated from the differential diagnostic point of view as a cause for the occurrence of erythema nodosum, a corresponding search for an infectious source is often recommended [11, 13]. However, among the various disorders and conditions which have been implicated in this distinctive hypersensitivity reaction during the past 25 years, only two references concern the association of dental infection and erythema nodosum [3, 20].
Case reports Case 1
The removal of dental deposits and curettage of the gingival pockets were performed in a 53-yearold woman because of superficial parodontitis, procedures associated with pronounced gingival bleeding. The patient's history revealed no other relevant disease. Four days following the dental treatment, round, extensive, erythematous nodules developed, 5-10 cm in diameter, initially on the left heel, afterwards on the right foot, expanding to the sides of the extensor muscles of the legs, arms, and buttocks. Additionally, the patient complained of arthralgias, myalgias, loss of appetite, and fever. Nine days after dental treatment, she was admitted to the hospital. On physical examination, a total of 12 partly red, partly livid, indistinctly limited nodular infiltrates were observed on the sides of the extensor muscles of both arms and legs, on the buttocks, and in the shoulder region. Body temperature was 39.4 ° C. Initial laboratory studies demonstrated an erythrocyte sedimentation rate (ESR) of 93/124 mm (Westergren method) and a leukocyte count of 15 300/mm 3. The antistreptolysin titer of 1:50 was within the normal range. Further investigations such as blood culture, complement status, rheumatoid serology, circulating immune complexes, serum electrophoresis, urinalysis, chest roentgenogram, sonography of the abdomen, and diagnostic procedures for detecting tuberculosis revealed no pathologic findings. Biopsy of one of the erythemas revealed the follow-
1074
Fig. 1. Erythema nodosum in the region of the right lower leg (case 2) Fig. 2. Erythema nodosum in the region of the right forearm (case 2)
ing histopathologic findings: transformation of subcutaneous fatty tissue into fatty tissue septa; expanding inflammatory infiltrates composed of neutrophilic granulocytes, lymphocytes, and histiocytes; and combinations of infiltrates varying in focus. Several multinuclear giant cells were present, and erythrocytic extravasation was noted. This led to a diagnosis of erythema nodosum. Two days after admission to hospital, the patient was treated orally with I g amoxycillin three times daily. Within 6 days of treatment her ESR dropped to 48/83 mm (Westergren). Leukocyte count and body temperature returned to normal. The erythema nodosum disappeared, and all other complaints subsided. Upon ambulant control 4 weeks later all laboratory findings had normalized. The patient has now been asymptomatic for 62 months. In conclusion, the diagnosis of an erythema nodosum caused by dental treatment involving gingival bleeding was established.
Case 2
A 52-year-old woman complained of recurrent fever up to 38.5 ° C and recurrent livid, red, painful, indurated swellings on both legs (Fig. 1). Arthralgias were reported to have occurred before the onset of the erythema nodosum on the respective extremities (knee and ankle joints). Many diagnostic procedures were performed without any results. Thereafter, the patient was admitted to our hospital. Three erythematous nodules measuring 8 x
15 cm were found on both lower legs in the cutaneous/subcutaneous tissue of the right forearm (Fig. 2). Her temperature was 38.5 ° C. Laboratory investigations showed: ESR of 87/130 m m (Westergren), positive C reactive protein and H L A B27, and a 13.1% increase in e2-globulins (Table 1). A stool culture revealed the presence of Yersinia enterocolitica (serogroup 3) three times within 7 days. Initially, Widal's serum test on Y. enterocolitica (serogroup 3) gave a positive reading at 1:640; 6 days later it was positive at 1 : 320. A biopsy from one erythematous nodule showed nodular vasculitis with a few eosinophilic granulocytes. No bone destruction of knee or ankle joints appeared on X-rays. The patient was diagnosed as having erythema nodosum due to a Yersinia infection. Daily oral therapy with 100 mg doxycycline was initiated. After I month of this treatment, erythematous nodules and arthralgias disappeared, and the body temperature normalized. The ESR dropped to 23/41 m m (Westergren) after 30 days. Six weeks later, however, body temperature rose again to 38 ° C. Arthralgias, weakness and recurrent erythema nodosum reccurred, but a stool examination and the Widal reaction failed to reveal any more signs of Yersinia infection. ESR was 50/ 83 mm (Westergren). A search for other infectious foci and/or hemato-oncological diseases, as well as further diagnostic investigations (e.g., for sarcoidosis) did not lead to any result. Another 4-week treatment with doxycycline was not associated with any improvement in the patient's symptoms or laboratory parameters.
1075 Table 1. Clinical data for (female) patients with erythema nodosum of dental origin Case
Age (years)
Body temperature
Leukocytes (per mm 3)
Thrombocytes (per mm 3)
AST
1
53
39.4
93/124
15300
362000
1:50
2
52
38.5
87/130
9600
312000
1:400
3
36
38.9
118/123
11800
867000
4
62
37.9
97/113
14400
234000
(of)
ESR (ram)
CRP
~2-Globulin Dental (%) treatment
Dental source
11.6
Removal of dental deposits
+
13.1
Tooth extraction
Relicted root 27, dental foci 34, 46
1:100
+
19.0
Root filling
Apical periodontitis 46
1:400
+
17.1
Tooth extraction
Apical periodontitis 14
ESR, Erythrocyte sedimentation rate; AST, Antistreptolysin titer; CRP, C reactive protein
Finally, she was admitted to our dental unit. Decayed teeth were noted which were painful on percussion (foci 34, 46). Panoramic roentgenography of the maxilla and mandible revealed a relicted dental root (27; Fig. 3). At 46, apical periodontitis was found. Thereupon, the extractions of 34, 46, and dental root 27 were performed. The patient was treated orally during and after extraction with I g amoxycillin three times daily. She has now been asymptomatic for 5 years. Erythema nodosum and arthralgias did not reccur. Her general condition, ESR, and body temperature remain normal. In conclusion, the diagnosis of recurrent erythema nodosum was attributed to chronic pulpitis, apical periodontitis, and a relicted root. Case 3
A 36-year-old woman was admitted to our hospital because of fever up to 38.9 ° C, arthralgias, and erythema nodosum which had existed for 10 days. About 1 week before the onset of these symptoms, the patient's dentist had administered a temporary root filling to a pulpitic molar (46; Fig. 4). Despite signs of apical periodontitis, the patient had not returned to her dentist after the temporary filling for permanent treatment of this tooth. Upon admission to hospital, the patient's body temperature was 38.2 ° C. Multiple erythematous, partly confluent lesions in the cutaneous/subcutaneous tissue of the lower legs and forearms and on the upper back were observed. They were livid, nodular, painful, and about 3 x 3 cm in size. Laboratory investigations revealed: ESR 118/123 mm (Wester-
gren), leukocyte count 11 800/mm 3, thrombocyte level 867000/mm 3, c~2-globulins 19.0%, slightly elevated C reactive protein, glutamyl transpeptidase 107 U/l, glutamic oxaloacetic transaminase 39 U/l, and glutamic pyruvic transaminase 86 U/1. Additional laboratory parameters (including antistreptolysin titer), immunological, sonographic, and radiological investigations all proved normal. Sarcoidosis, tuberculosis, Crohn's disease, and ulcerative colitis were specifically excluded as causes of the erythema nodosum. The patient was sent to the hospital dentist who found generalized marginal superficial periodontitis, apical periodontitis at 46 and 47, and incomplete root fillings at 15, 25, and 26 (Fig. 4). Initially, the superficial periodontitis was treated, and extractions of 46 and 47 were performed. Oral antibiotic treatment with I g amoxycillin three times daily for 10 days was prescribed. The patient's body temperature normalized by the fourth treatment day; during the following days arthralgias and erythema nodosum regressed. Twelve days after dental treatment ESR was 57/90 mm (Westergren), thrombocytes 622000/mm 3, and glutamic pyruvic transaminase 45 U/1. A liver biopsy performed at that time revealed no signs of inflammatory infiltrates, epithelioid cell granulomas, or malignancies. One month after dental treatment, erythema nodosum had completely disappeared. The patient's general condition and all laboratory parameters including ESR (8/10 mm, Westergren method), leukocytes, thrombocytes, and transaminases had normalized. The patient has now been asymp-
1076
Fig. 3. X-rays of the maxilla and mandible: relicted root 27, deep distal caries with apical periodontitis 46 (case 2) Fig. 4. X-rays of the maxilla and mandible: apical periodontitis 46, 47; incomplete root filling 15, 25, and 26 (case 3)
tomatic for 5 years. In conclusion, the erythema nodosum was caused by dental infection: dental treatment with an incomplete root filling of a molar accompanied by apical periodontitis led to the exacerbation of the symptoms. Case 4
A 62-year-old woman had been complaining for 2 weeks of livid erythematous nodules (8 x 8 cm) on both lower legs. Three days before the occurrence of the erythematous nodules, a decayed gangrenous tooth (14) was fractured in the coronal region and had been extracted immediately there after by a dentist. On admission to our hospital 14 days after the onset of the erythema nodosum, the patient complained of weakness, weight loss (2.5 kg during the preceding 2 weeks), and nocturnal sweating. Body temperature was 37.9 ° C. A li-
vid node in the region of the left calf measuring 6 x 8 cm which was painful on palpation was seen. Additionally, redness, swelling, and arthralgia of the left wrist joint were noted. The laboratory work-up indicated: ESR 97/113 m m (Westergren), leukocytes 14 400/mm 3, antistreptolysin titer I : 400. Although the extraction wound at 14 was not infected, an X-ray revealed apical periodontitis in this area. Two days after the initial investigation, oral antibiotic treatment with 1 g amoxycillin three times daily was started for 10 days (3 x 2 g for the first 2 days). Thereupon, the patient's general condition, body temperature, and leukocytes normalized; the swelling of the left wrist joint and the erythema nodosum completely disappeared. At an ambulant control 4 weeks later ESR was normal. Other possible reasons for the erythema nodosum such as tuberculosis, Crohn's disease, sarcoidosis,
1077
Yersinia infection, ulcerative colitis, Beh~et's syndrome, etc. had been excluded. The patient has now been asymptomatic for 6 years. In conclusion, the diagnosis of an erythema nodosum following extraction of a decayed gangrenous tooth was established. Discussion
In all four cases it was remarkable that both the physicians who had first seen these patients and those who had initially examined them at our hospital failed to consider a possible oral or dental origin for the erythema nodosum. Indeed, it was only after a meticulous (re)evaluation of the medical history that proper attention was directed to dental foci as well as to the preceding dental treatment. Consequently, we consider it necessary to emphasize the possible importance of dental factors leading to erythema nodosum. Furthermore, a retrospective literature search over the last 25 years revealed only two studies on the association of erythema nodosum and dental foci with streptococcal involvement [3, 20] despite the fact that this possibility is mentioned in some medical textbooks [11, 13]. All four patients described in this report were women. The ESR were maximally elevated with more than 80 m m (Westergren) after the Ist h. Fever, weakness, and arthralgias were reported, and leukocytosis and thrombocytosis were generally present (Table 1), The time interval between the onset of the erythema nodosum and the preceding dental treatment ranged from 3 to 10 days. These observations are in accordance with those of Bernacka et al. [3] who reported 11 cases with streptococcal infections and erythema nodosum. F o u r women in that report had dental infectious loci (three cases of relicted roots with apical periodontitis, one with gangrenous pulpitis). These authors described also only female patients between 28 and 44 years of age (similar to those with systemic lupus erythrematosus) who had ESR values of up to 118/159 mm (Westergren). As in our cases, the antistreptolysin titers were not always positive. They concluded that the diagnostic procedures were made more difficult because no dental lesions were clinically apparent, and that only X-ray images produce diagnostically and therapeutically relevant results Analogously, other authors have identified "occult dental infections" (apical periodontitis) as reasons for arthritis or fever of unknown origin [4, 12, 14]. Apical periodontitis is a chronic, asymptomatic form of a localized infection which
in contrast to dental abscesses associated with redness, swelling, pain, and fever - is not thought to lead to bacterial invasion into the bloodstream. Streptococci are mostly responsible for infectious diseases of dental origin [1, 5, 7, 10, 18]. They may cause symptoms and such diseases as erythema nodosum, infective arthritis, fever of unknown origin, glomerulonephritis, or bacterial endocarditis [4, 12, 14]. Following treatment of the infectious focus (by tooth extraction, root resection, antibiotic therapy) the patient's symptoms generally disappear, meaning that the underlying apical periodontitis must be the reason for the observed disease [4, 12, 14]. A more evident connection, however, is that of gingival bleeding associated dental treatment (e.g., extractions or removal of dental deposits) and the development of bacteremia [10]. As early as 1935 Okell et al. [18] reported the occurrence of Streptococcus viridans bacteremia following tooth extractions. Investigators have found transient streptococci-positive blood cultures in up to 61% of patients following tooth extractions [1, 5, 7] immediately after and up to 8 h following these procedures, with body temperatures measuring between 37.5 ° and 38.5° C (onset 5-9 h after extraction, lasting for about 3 h). Mombelli [16] found transient bacteremia following dental treatment with gingival bleeding in no less than 80% of patients. Various theories have been proposed concerning the association of dental involvement in erythema nodosum and its mechanism of action [6, 8, 9]. Here, the concept of focal infection, first used in 1930 by P/il31er [19], and that of focal allergy [2, 17] are worth mentioning. There is always a spatial separation between the origin of the inflammatory process and the antigen deposit [15]. In conclusion, these case reports indicate that dental procedures associated with gingival bleeding and with clinically asymptomatic but infectious dental foci such as those involved in apical periodontitis may lead to the occurrence of erythema nodosum.
-
References
1. Baltch AL, Schaffer C, Mark RDH, Hammer MC, Sutphen NT, Smith RP, Conroy J, Shayegani M (1982) Bacteremia following dental cleaning in patients with and without penicillin prophylaxis. Am Heart J 104:1335 1339 2. Berger W (1939) Die fokale Infektion als Problem der Allergic. Verh Dtsch Ges Inn Med 51:455-486 3. Bernacka K, Chwal Z, Stasiewicz A (1977) Analiza przypadkow rumienia guzowatego leczonych w latach 1974~1975 w oddziale reumatologicznym w Bialymstoku. Pol Tyg Lek 32: 197-200
1078 4. Berry E, Silver J (1976) Pyorrhoea as a cause of pyrhexia. BMJ 2:1289-1290 5. Cawson RA (1981) Infective endocarditis as a complication of dental treatment. Br Dent J 151:409-414 6. G/irtner F (1977) Das Herdproblem aus 0dontologischer Sicht. Zahn/irztl Welt 86:461-466 7. Harvey WP, Capone MA (1961) Bacterial endocarditis related to cleaning and filling of teeth. Am J Cardiol 17:793798 8. Haunfelder D (1975) Die Bedeutung des sogenannten Herdgeschehens fiir den Zahnarzt. In: Haunfelder D, Hupfauf L, Ketterl W, Schmuth G (eds) Praxis der Zahnheilkunde. Urban und Schwarzenberg, Munich, vol 4, sect E2, pp 1-34 9. Ketterl W (1983) Die Theorien zur Herderkrankung: Kritik und Standort-Bestimmung. Zahnfirztl Mitt 73:2083-2085 10. Kirch W (1985) Innere Medizin und Zahnheilkunde. Interdisziplin/ire Aspekte. Diagnostik 18: 21-23 11. Kirch W (1987) Innere Medizin und Zahnheilkunde. Carl Hanser, Munich, pp 171-172 12. Kirch W, Kasperk E-M, Proppe D, Diihrsen U, Ohnhaus EE (1988) Unterschiedliche klinische Manifestationen mit dentogener Ursache. Med Klinik 83 : 790-794 13. Kriiger E (1983) Lehrbuch der chirurgischen Zahn-, Mundund Kieferheilkunde, vol I. Quintessenz, Berlin 14. Levinson SL, Barondess JA (1979) Occult dental infection as a cause of fever of obscure origin. Am J Med 66 : 463467 15. Matzen (1987) Die Atiologie des dentogenen Herdgesche-
hens, betrachtet in einer Modelluntersuchung zur Fernwirkung intradental applizierter Immunogene. Inaugural dissertation, University of Kiel 16. Mombelli G (1984) Endokarditis-Prophylaxe und -Therapie. Schweiz Med Wochenschr 114:73-77 17. Miiller-Ruchholtz W, Matzen U (1987) Die Immunologie des sogenannten Herdgeschehens. Dtsch Zahn/irztl Z 42:177-182 18. Okell BC, Camb MB, Elliott SD (1935) Bacteraemia and oral sepsis with special reference to the aetiology of subacute endocarditis. Lancet II: 869-872 19. P/il31erH (1930) Ober Herdinfektion, Klinische Grundlagen und Probleme. Verh Dtsch Ges Inn Med 42:381-408 20. Uehlinger E (1971) L'infezione focale. Riv Ital Stomatol 26:3947 Received: July 17, 1992 Returned for revision: September 1, 1992 Accepted: September 15, 1992 Prof. Dr. Dr. W. Kirch Medizinische Klinik Christian-Albrechts-Universit/it Schittenhelmstrasse 12 W-2300 Kiel 1, FRG
Clin Investig (1992) 70:1073 1078
Case Report
© Springer-Verlag 1992
Erythema nodosum of dental origin W. Kirch 1 and U. Diihrsen 2 I Medizinische Klinik, Christian-Albrechts-UniversitS.t Kiel 2 H Medizinische Klinik, Universit/itskrankenhaus Hamburg, Eppendorf
Summary. The association of erythema nodosum and dental infectious foci has rarely been described in the literature. This report concerns four women who developed erythema nodosum either following dental treatment associated with gingival bleeding or due to infectious dental foci. In these cases, tooth extraction, removal of dental deposits, interrupted pulp treatment, apical periodontitis, or a relicted root were identified as causes of the development of erythema nodosum. Upon admission to the hospital, these patients also presented fever and and a maximally elevated erythrocyte sedimentation rate (ESR). In all instances, surgical treatment of the dental foci and/or administration of antibiotics rapidly led to the regression of the erythema nodosum, as well as to the normalization of body temperature and ESR. The cases described indicate that antecedent dental treatment and the possible presence of infectious dental loci should be considered in the differential diagnosis of erythema nodosum when taking the patient's medical history. This approach may avoid unnecessary, possibly invasive diagnostic procedures and can lead to rapid improvement in the patient's clinical status.
Key words: Erythema nodosum - Dental origin Dental infectious foci
Erythema nodosum is characterized by recurrent, painful, livid, nodular perivascular infiltrates measuring up to 10 x 10 cm which tend to be localized in the cutaneous/subcutaneous tissue, preferentially on the lower extremities. From the etiological point of view, this syndrome has been associated with tuberculosis, sarcoidosis, infectious intestinal diseases, rheumatoid diseases, and drug allergies. Frequently, the origin of an erythema nodosum cannot be ascertained; it is then termed idiopathic erythema nodosum. As streptococcal and staphylococcal (e.g., oropharyngeal) infections have been Abbreviations: ESR = erythrocyte sedimentation rate
implicated from the differential diagnostic point of view as a cause for the occurrence of erythema nodosum, a corresponding search for an infectious source is often recommended [11, 13]. However, among the various disorders and conditions which have been implicated in this distinctive hypersensitivity reaction during the past 25 years, only two references concern the association of dental infection and erythema nodosum [3, 20].
Case reports Case 1
The removal of dental deposits and curettage of the gingival pockets were performed in a 53-yearold woman because of superficial parodontitis, procedures associated with pronounced gingival bleeding. The patient's history revealed no other relevant disease. Four days following the dental treatment, round, extensive, erythematous nodules developed, 5-10 cm in diameter, initially on the left heel, afterwards on the right foot, expanding to the sides of the extensor muscles of the legs, arms, and buttocks. Additionally, the patient complained of arthralgias, myalgias, loss of appetite, and fever. Nine days after dental treatment, she was admitted to the hospital. On physical examination, a total of 12 partly red, partly livid, indistinctly limited nodular infiltrates were observed on the sides of the extensor muscles of both arms and legs, on the buttocks, and in the shoulder region. Body temperature was 39.4 ° C. Initial laboratory studies demonstrated an erythrocyte sedimentation rate (ESR) of 93/124 mm (Westergren method) and a leukocyte count of 15 300/mm 3. The antistreptolysin titer of 1:50 was within the normal range. Further investigations such as blood culture, complement status, rheumatoid serology, circulating immune complexes, serum electrophoresis, urinalysis, chest roentgenogram, sonography of the abdomen, and diagnostic procedures for detecting tuberculosis revealed no pathologic findings. Biopsy of one of the erythemas revealed the follow-
1074
Fig. 1. Erythema nodosum in the region of the right lower leg (case 2) Fig. 2. Erythema nodosum in the region of the right forearm (case 2)
ing histopathologic findings: transformation of subcutaneous fatty tissue into fatty tissue septa; expanding inflammatory infiltrates composed of neutrophilic granulocytes, lymphocytes, and histiocytes; and combinations of infiltrates varying in focus. Several multinuclear giant cells were present, and erythrocytic extravasation was noted. This led to a diagnosis of erythema nodosum. Two days after admission to hospital, the patient was treated orally with I g amoxycillin three times daily. Within 6 days of treatment her ESR dropped to 48/83 mm (Westergren). Leukocyte count and body temperature returned to normal. The erythema nodosum disappeared, and all other complaints subsided. Upon ambulant control 4 weeks later all laboratory findings had normalized. The patient has now been asymptomatic for 62 months. In conclusion, the diagnosis of an erythema nodosum caused by dental treatment involving gingival bleeding was established.
Case 2
A 52-year-old woman complained of recurrent fever up to 38.5 ° C and recurrent livid, red, painful, indurated swellings on both legs (Fig. 1). Arthralgias were reported to have occurred before the onset of the erythema nodosum on the respective extremities (knee and ankle joints). Many diagnostic procedures were performed without any results. Thereafter, the patient was admitted to our hospital. Three erythematous nodules measuring 8 x
15 cm were found on both lower legs in the cutaneous/subcutaneous tissue of the right forearm (Fig. 2). Her temperature was 38.5 ° C. Laboratory investigations showed: ESR of 87/130 m m (Westergren), positive C reactive protein and H L A B27, and a 13.1% increase in e2-globulins (Table 1). A stool culture revealed the presence of Yersinia enterocolitica (serogroup 3) three times within 7 days. Initially, Widal's serum test on Y. enterocolitica (serogroup 3) gave a positive reading at 1:640; 6 days later it was positive at 1 : 320. A biopsy from one erythematous nodule showed nodular vasculitis with a few eosinophilic granulocytes. No bone destruction of knee or ankle joints appeared on X-rays. The patient was diagnosed as having erythema nodosum due to a Yersinia infection. Daily oral therapy with 100 mg doxycycline was initiated. After I month of this treatment, erythematous nodules and arthralgias disappeared, and the body temperature normalized. The ESR dropped to 23/41 m m (Westergren) after 30 days. Six weeks later, however, body temperature rose again to 38 ° C. Arthralgias, weakness and recurrent erythema nodosum reccurred, but a stool examination and the Widal reaction failed to reveal any more signs of Yersinia infection. ESR was 50/ 83 mm (Westergren). A search for other infectious foci and/or hemato-oncological diseases, as well as further diagnostic investigations (e.g., for sarcoidosis) did not lead to any result. Another 4-week treatment with doxycycline was not associated with any improvement in the patient's symptoms or laboratory parameters.
1075 Table 1. Clinical data for (female) patients with erythema nodosum of dental origin Case
Age (years)
Body temperature
Leukocytes (per mm 3)
Thrombocytes (per mm 3)
AST
1
53
39.4
93/124
15300
362000
1:50
2
52
38.5
87/130
9600
312000
1:400
3
36
38.9
118/123
11800
867000
4
62
37.9
97/113
14400
234000
(of)
ESR (ram)
CRP
~2-Globulin Dental (%) treatment
Dental source
11.6
Removal of dental deposits
+
13.1
Tooth extraction
Relicted root 27, dental foci 34, 46
1:100
+
19.0
Root filling
Apical periodontitis 46
1:400
+
17.1
Tooth extraction
Apical periodontitis 14
ESR, Erythrocyte sedimentation rate; AST, Antistreptolysin titer; CRP, C reactive protein
Finally, she was admitted to our dental unit. Decayed teeth were noted which were painful on percussion (foci 34, 46). Panoramic roentgenography of the maxilla and mandible revealed a relicted dental root (27; Fig. 3). At 46, apical periodontitis was found. Thereupon, the extractions of 34, 46, and dental root 27 were performed. The patient was treated orally during and after extraction with I g amoxycillin three times daily. She has now been asymptomatic for 5 years. Erythema nodosum and arthralgias did not reccur. Her general condition, ESR, and body temperature remain normal. In conclusion, the diagnosis of recurrent erythema nodosum was attributed to chronic pulpitis, apical periodontitis, and a relicted root. Case 3
A 36-year-old woman was admitted to our hospital because of fever up to 38.9 ° C, arthralgias, and erythema nodosum which had existed for 10 days. About 1 week before the onset of these symptoms, the patient's dentist had administered a temporary root filling to a pulpitic molar (46; Fig. 4). Despite signs of apical periodontitis, the patient had not returned to her dentist after the temporary filling for permanent treatment of this tooth. Upon admission to hospital, the patient's body temperature was 38.2 ° C. Multiple erythematous, partly confluent lesions in the cutaneous/subcutaneous tissue of the lower legs and forearms and on the upper back were observed. They were livid, nodular, painful, and about 3 x 3 cm in size. Laboratory investigations revealed: ESR 118/123 mm (Wester-
gren), leukocyte count 11 800/mm 3, thrombocyte level 867000/mm 3, c~2-globulins 19.0%, slightly elevated C reactive protein, glutamyl transpeptidase 107 U/l, glutamic oxaloacetic transaminase 39 U/l, and glutamic pyruvic transaminase 86 U/1. Additional laboratory parameters (including antistreptolysin titer), immunological, sonographic, and radiological investigations all proved normal. Sarcoidosis, tuberculosis, Crohn's disease, and ulcerative colitis were specifically excluded as causes of the erythema nodosum. The patient was sent to the hospital dentist who found generalized marginal superficial periodontitis, apical periodontitis at 46 and 47, and incomplete root fillings at 15, 25, and 26 (Fig. 4). Initially, the superficial periodontitis was treated, and extractions of 46 and 47 were performed. Oral antibiotic treatment with I g amoxycillin three times daily for 10 days was prescribed. The patient's body temperature normalized by the fourth treatment day; during the following days arthralgias and erythema nodosum regressed. Twelve days after dental treatment ESR was 57/90 mm (Westergren), thrombocytes 622000/mm 3, and glutamic pyruvic transaminase 45 U/1. A liver biopsy performed at that time revealed no signs of inflammatory infiltrates, epithelioid cell granulomas, or malignancies. One month after dental treatment, erythema nodosum had completely disappeared. The patient's general condition and all laboratory parameters including ESR (8/10 mm, Westergren method), leukocytes, thrombocytes, and transaminases had normalized. The patient has now been asymp-
1076
Fig. 3. X-rays of the maxilla and mandible: relicted root 27, deep distal caries with apical periodontitis 46 (case 2) Fig. 4. X-rays of the maxilla and mandible: apical periodontitis 46, 47; incomplete root filling 15, 25, and 26 (case 3)
tomatic for 5 years. In conclusion, the erythema nodosum was caused by dental infection: dental treatment with an incomplete root filling of a molar accompanied by apical periodontitis led to the exacerbation of the symptoms. Case 4
A 62-year-old woman had been complaining for 2 weeks of livid erythematous nodules (8 x 8 cm) on both lower legs. Three days before the occurrence of the erythematous nodules, a decayed gangrenous tooth (14) was fractured in the coronal region and had been extracted immediately there after by a dentist. On admission to our hospital 14 days after the onset of the erythema nodosum, the patient complained of weakness, weight loss (2.5 kg during the preceding 2 weeks), and nocturnal sweating. Body temperature was 37.9 ° C. A li-
vid node in the region of the left calf measuring 6 x 8 cm which was painful on palpation was seen. Additionally, redness, swelling, and arthralgia of the left wrist joint were noted. The laboratory work-up indicated: ESR 97/113 m m (Westergren), leukocytes 14 400/mm 3, antistreptolysin titer I : 400. Although the extraction wound at 14 was not infected, an X-ray revealed apical periodontitis in this area. Two days after the initial investigation, oral antibiotic treatment with 1 g amoxycillin three times daily was started for 10 days (3 x 2 g for the first 2 days). Thereupon, the patient's general condition, body temperature, and leukocytes normalized; the swelling of the left wrist joint and the erythema nodosum completely disappeared. At an ambulant control 4 weeks later ESR was normal. Other possible reasons for the erythema nodosum such as tuberculosis, Crohn's disease, sarcoidosis,
1077
Yersinia infection, ulcerative colitis, Beh~et's syndrome, etc. had been excluded. The patient has now been asymptomatic for 6 years. In conclusion, the diagnosis of an erythema nodosum following extraction of a decayed gangrenous tooth was established. Discussion
In all four cases it was remarkable that both the physicians who had first seen these patients and those who had initially examined them at our hospital failed to consider a possible oral or dental origin for the erythema nodosum. Indeed, it was only after a meticulous (re)evaluation of the medical history that proper attention was directed to dental foci as well as to the preceding dental treatment. Consequently, we consider it necessary to emphasize the possible importance of dental factors leading to erythema nodosum. Furthermore, a retrospective literature search over the last 25 years revealed only two studies on the association of erythema nodosum and dental foci with streptococcal involvement [3, 20] despite the fact that this possibility is mentioned in some medical textbooks [11, 13]. All four patients described in this report were women. The ESR were maximally elevated with more than 80 m m (Westergren) after the Ist h. Fever, weakness, and arthralgias were reported, and leukocytosis and thrombocytosis were generally present (Table 1), The time interval between the onset of the erythema nodosum and the preceding dental treatment ranged from 3 to 10 days. These observations are in accordance with those of Bernacka et al. [3] who reported 11 cases with streptococcal infections and erythema nodosum. F o u r women in that report had dental infectious loci (three cases of relicted roots with apical periodontitis, one with gangrenous pulpitis). These authors described also only female patients between 28 and 44 years of age (similar to those with systemic lupus erythrematosus) who had ESR values of up to 118/159 mm (Westergren). As in our cases, the antistreptolysin titers were not always positive. They concluded that the diagnostic procedures were made more difficult because no dental lesions were clinically apparent, and that only X-ray images produce diagnostically and therapeutically relevant results Analogously, other authors have identified "occult dental infections" (apical periodontitis) as reasons for arthritis or fever of unknown origin [4, 12, 14]. Apical periodontitis is a chronic, asymptomatic form of a localized infection which
in contrast to dental abscesses associated with redness, swelling, pain, and fever - is not thought to lead to bacterial invasion into the bloodstream. Streptococci are mostly responsible for infectious diseases of dental origin [1, 5, 7, 10, 18]. They may cause symptoms and such diseases as erythema nodosum, infective arthritis, fever of unknown origin, glomerulonephritis, or bacterial endocarditis [4, 12, 14]. Following treatment of the infectious focus (by tooth extraction, root resection, antibiotic therapy) the patient's symptoms generally disappear, meaning that the underlying apical periodontitis must be the reason for the observed disease [4, 12, 14]. A more evident connection, however, is that of gingival bleeding associated dental treatment (e.g., extractions or removal of dental deposits) and the development of bacteremia [10]. As early as 1935 Okell et al. [18] reported the occurrence of Streptococcus viridans bacteremia following tooth extractions. Investigators have found transient streptococci-positive blood cultures in up to 61% of patients following tooth extractions [1, 5, 7] immediately after and up to 8 h following these procedures, with body temperatures measuring between 37.5 ° and 38.5° C (onset 5-9 h after extraction, lasting for about 3 h). Mombelli [16] found transient bacteremia following dental treatment with gingival bleeding in no less than 80% of patients. Various theories have been proposed concerning the association of dental involvement in erythema nodosum and its mechanism of action [6, 8, 9]. Here, the concept of focal infection, first used in 1930 by P/il31er [19], and that of focal allergy [2, 17] are worth mentioning. There is always a spatial separation between the origin of the inflammatory process and the antigen deposit [15]. In conclusion, these case reports indicate that dental procedures associated with gingival bleeding and with clinically asymptomatic but infectious dental foci such as those involved in apical periodontitis may lead to the occurrence of erythema nodosum.
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References
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