http://informahealthcare.com/cot ISSN: 1556-9527 (print), 1556-9535 (electronic) Cutan Ocul Toxicol, Early Online: 1–4 ! 2015 Informa Healthcare USA, Inc. DOI: 10.3109/15569527.2015.1067818
RESEARCH ARTICLE
Cutaneous anthrax: evaluation of 28 cases in the Eastern Anatolian region of Turkey
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Affan Denk1, Ayse Sagmak Tartar2, Mehmet Ozden1, Betul Demir3, and Ayhan Akbulut1 1
Department of Infectious Diseases and Clinical Microbiology, Faculty of Medicine, Firat University, Elazig, Turkey, 2Department of Infectious Diseases and Clinical Microbiology, Cizre State Hospital, Sirnak, Turkey, and 3Department of Dermatology, Faculty of Medicine, Firat University, Elazig, Turkey Abstract
Keywords
Context: Anthrax is an endemic disease in developing countries. Human cases are usually associated with animal products. About 95% of naturally acquired cases are cutaneous anthrax. Objective: In this study, cutaneous anthrax cases from the Elazig province (the Eastern Anatolian region) of Turkey seen in our hospital within a 6-year period were evaluated with respect to epidemiological and clinical features, diagnosis, treatment and outcome. Methods: Twenty-eight patients with cutaneous anthrax observed between January 2009 and December 2014 were investigated retrospectively. The diagnosis of cutaneous anthrax was based on detailed history, dermatologic findings, including painless, ulcers covered by a characteristic black eschar and/or microbiological procedures, including Gram stain and culture of materials obtained from the lesions. Results: Of the 28 patients followed up with cutaneous anthrax diagnosis, 14 (50%) were female and 14 (50%) were male. The mean age of the cases was 39.6 years (age range 17–65 years). The patients have an incubation period in the range of 1–9 days (mean 4.6 ± 0.5 days). The cases were seen between April and November of each year during the study period. Twenty-three cases (82%) had a history of contact with animals or animal products. Twenty patients (71.4%) showed malignant pustules and eight (28.6%) malignant edema. Bacillus anthracis was isolated in three cases (10.7%) and Gram stain smear were positive in five cases (17.8%). All patients were treated successfully with penicillin or ciprofloxacin. Systemic corticosteroids were added to the antibiotic treatment in six patients with malignant edema. Sepsis no developed in patients, all the cases recovered. Conclusion: Anthrax is still a serious public health problem in Turkey. Cutaneous anthrax must always be kept in mind when characteristic lesions such as a painless ulcer with vesicles, edema, and a history of contact with animals or animal products are observed in an individual. Early and correct diagnosis significantly affects course of the disease. Protective precautions such as vaccination of animals against anthrax and education of the population would reduce the incidence of the disease.
Cutaneous anthrax, endemic disease, outcome, zoonosis
Introduction Anthrax is a zoonotic infectious disease caused by Bacillus anthracis that is an aerobic, Gram-positive, endosporeforming, nonmotile, capsulated, rod-shaped bacterium. In nature, anthrax primarily affects domestic animals such as sheep, goats and cattle1. Humans almost invariably contract the natural disease directly or indirectly from animals or animal products. There are three forms of naturally occurring human anthrax infection; cutaneous, gastrointestinal and inhalational anthrax. Among these clinical forms of anthrax, cutaneous anthrax is most frequent. Cutaneous anthrax typically occurs as a result
Address for correspondence: Dr. Affan Denk, Department of Infectious Diseases and Clinical Microbiology, Faculty of Medicine, Firat University, Elazig 23119, Turkey. E-mail: [email protected]
History Received 5 May 2015 Revised 15 June 2015 Accepted 26 June 2015 Published online 30 July 2015
of exposure to anthrax-infected animals or their products. Cutaneous anthrax could also occur as a result of an aerosol attack2–4. In recent 20 years, B. anthracis come to the fore as potential agent of biological warfare5,6. Anthrax is an infection that prevalence is gradually decreasing in the world. Human anthrax is seen most commonly in Indian Subcontinent, Africa, The Middle East and Latin America. Further, it has also been reported from Zimbabwe, Bangladesh, USA, South Africa, Iraq, Iran and Turkey3,7. The largest outbreak of anthrax known in humans occurred in Zimbabwe, approximately 10 000 cases between 1979 and 1980 leading to 182 deaths8. In developed (industrialized) countries, human anthrax cases are rarely seen9. In the present retrospective study, 28 cases of cutaneous anthrax seen in Firat University Hospital in the Eastern Anatolian region of Turkey between January 2009 and
2
A. Denk et al.
December 2014 were evaluated with respect to epidemiological and clinical features, diagnosis, treatment and outcome.
Cutaneous and Ocular Toxicology Downloaded from informahealthcare.com by Nyu Medical Center on 07/31/15 For personal use only.
Patients and methods The records of 28 cutaneous anthrax cases observed in Firat University Hospital (inpatient the Departments of Infectious Diseases and Dermatology) between January 2009 and December 2014 were examined. Patients were from the Elazig province in the Eastern Anatolian Region of Turkey. The diagnosis of cutaneous anthrax was based on detailed history, dermatologic findings, including painless ulcers covered by a characteristic black eschar and/or microbiological procedures, including Gram stain and culture of materials obtained from the lesions. Self-reported source of infection was determined from categorical responses that included butchering/slaughtering cattle, handling/preparing meat, exposure to a sick animal or to contaminated animal products, exposure to an insect bite and unknown. Age, sex, occupation, the time of onset of the first lesion, antimicrobial therapy received prior to admission, localization, and type of lesions, clinical history, antibiotic treatment, duration of therapy, and outcome were recorded. Samples such as vesicular or bullous fluid taken from the lesions were cultured on 5% sheep blood agar. In addition, blood samples were cultured in an automated blood culture system (Becton Dickinson, Franklin Lakes, NJ) in some patients with fever. Bacillus anthracis was identified by traditional microbiological methods, and also confirmed using Vitek 2 (BioMerieux, Marcy l’Etoile, France) automated identification system. Large white to gray nonhemolytic colonies with irregularly tapered outgrowths were evaluated. Gram stain showed rod-shaped bacteria growing as long chains.
Cutan Ocul Toxicol, Early Online: 1–4
Table 1. The age and gender distribution of the cases. Age range
Female
Male
Total
519 20–29 30–39 40–49 50–59 460 Total (%)
0 0 6 2 3 3 14 (50)
1 6 3 3 0 1 14 (50)
1 6 9 5 3 4 28 (100)
Figure 1. The distribution of cases according to months.
Results Of the 28 patients followed up with cutaneous anthrax diagnosis, 14 (50%) were female and 14 (50%) were male. The mean age of the cases was 39.6 ± 12.6 years (age range 17–65 years). More than half of the cases were in the agegroups 20–29 and 30–39 years. The age and gender distribution of the cases are shown in Table 1. The cases were seen between April and November of each year during the study period, August (28.5%) and September (28.5%) were the most intensive months (Figure 1). Twenty-three cases (82%) had a history of contact with sick cows or sheep, animal slaughtering, skin peeling, meat processing or helping in one of these activities. Three of these cases were butcher. Five cases (18%) did not any history of contact with animals or animal products. The patients have an incubation period in the range of 1–9 days (mean 4.6 ± 0.5 days). All cases in our study were cutaneous anthrax; 20 (71.4%) patients showed malignant pustules located on the hands/fingers and arms. Eight (28.6%) patients exhibited with malignant edema with lesions located on the face/neck and arms (Figures 2 and 3). Localization of the lesions in the 28 cases is given in Table 2. Bacillus anthracis was isolated from vesicular/bullous fluid cultures in three cases (10.7%) and Gram stain smear
Figure 2. Malignant pustule. A characteristic necrotic lesion surrounded by blisters and edema on the left hand.
were positive for Gram-positive rods of B. anthracis in five cases (17.8%). Culture and Gram stain smear were both positive in three (10.7%) of these cases. Blood cultures taken for all patients with fever were negative. Seventeen patients
Cutaneous anthrax
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DOI: 10.3109/15569527.2015.1067818
Figure 3. Malignant edema. Lesions on the right and left eyelids are accompanied by swelling of the lips and face. Table 2. Localization of skin lesions in the cases. Localization of skin lesions
No. (%)
Hands and fingers Wrists and arms Eyelids and face Neck Total
18 6 3 1 28
(64.3) (21.4) (10.7) (3.6) (100)
(60.7%) had received an antibiotic before admission to our hospital. Bacillus anthracis was not demonstrated in Gram stain smear or culture taken from the lesions in these 17 patients. All of the patients were treated successfully with penicillin or ciprofloxacin. In the treatment of patients with malignant pustules, procaine penicillin G (2 800 000 IU/day) in 14 patients and oral ciprofloxacin (2 750 mg/day) in six patients was used for 7–10 days. Eight patients with malignant edema presentation were treated initially with intravenous penicillin G (8 3 million IU/day) for 5 days, followed by intramuscular procaine penicillin (2 800 000 IU/day) for afterwards 5 days. Systemic corticosteroids (i.v. methyl prednisolone 1–2 mg/kg/day or i.v. dexamethasone 32 mg/day) were added to the antibiotic treatment in six patients with malignant edema. Sepsis no developed in patients, all the cases recovered.
Discussion Human anthrax is not a major problem of health in developed countries as only a few encounters are reported from such countries, but especially cutaneous anthrax is still a serious public health problem in developing countries like Turkey whose economy is principally agriculture dependent and
3
livestock is common2–4,10. Cutaneous anthrax accounts for approximately 95% of all reported human anthrax cases. It is known that anthrax has been for a long time in the Eastern Anatolia Region of Turkey where animal husbandry is the prime occupation. In Turkey, most of the anthrax cases (almost all) are in the cutaneous form2,3. The disease occurred about equally in women and men, in animal husbandry in rural areas4. In this study, there was no relationship between genders. Most of our cases were in 20–29 and 30–39 years according to the age-groups. People are exposed to infectious agent during transactions, such as butchering/slaughtering of the animal, processing/handling meat, cutting of meat and skinning2–4. In 23 our cases (82%), there was a history of direct or indirect contact by infected animal or animal products. The disease is generally reported in summer and autumn months11–13. In our study, cases occurred between April and November (the most frequent in August and September), because of animal slaughtering, meat cutting and meat roasting are usually realized. Anthrax cases no seen between December and March of each year during the study period. Cutaneous anthrax develops on exposed skin sites following a minor abrasion. Areas of exposed skin like hands, arms, face and neck were mostly affected14,15. Twenty (71.4%) patients exhibited malignant pustules located on the hands/ fingers and arms. Eight (28.6%) patients exhibited with malignant edema with lesions located on the face/neck and arms. Diagnosis of cutaneous anthrax first requires suspicion. In non-endemic areas, diagnosis may be difficult. If a patient has a typical painless pustule or extensive edema and a contact history with domestic animal, the diagnosis may be easy. The diagnosis is confirmed by detecting the agent microorganism in Gram stain or isolation of B. anthracis in the culture. Today, in addition to these, serological and molecular methods such as enzyme linked immunosorbent assay and polymerase chain reaction have been used5,12. The rate of positive anthrax cultures in the skin lesions does not exceed 60–65%9. After 24–48 h of the use of a potent antibiotic against B. anthracis, possibility of the growth of the microorganism in the cutaneous lesion has decreased2. In this study, in three cases (10.7%) material obtained from the lesion was culture positive. The majority of cases had been treated with antimicrobials before being admitted to our hospital. Seventeen cases (60.7%) had a history of antimicrobial use before admission to our hospital and B. anthracis was not demonstrated in Gram stain smear or culture taken from the lesions in these 17 patients. Three of 11 (27.2%) who had not taken antimicrobials were culture positive. Although these patients reported else, we suspect that some of their might have taken antimicrobials prior to admission. It is known that antimicrobials can be provided without prescription in our country. Diagnosis in all culture negative patients was made through history and physical examination. Penicillins, quinolones, tetracyclines, macrolides, aminoglycosides, carbapenems, rifampicin, vancomycin, clindamycin, chloramphenicol, linezolid, cefazolin and other first-generation cephalosporins are effective against in vitro human clinical isolates of B. anthracis. Topical therapy is not useful16–19. The recommended treatment of naturally
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A. Denk et al.
occurring cutaneous anthrax is generally first choice procaine penicillin G (0.6–1.2 million IU IM every 12–24 h) or benzyl penicillin G (4 mU IV every 4–6 h) or amoxicillin (500 mg oral every 6–8 h), alternatively ciprofloxacin (500–750 mg oral every 12 h, 200–400 mg IV every 12 h) or doxycycline (100 mg oral every 12 h). Antimicrobial therapy should be used orally in mild cutaneous anthrax. In cases of severe cutaneous anthrax or systemic anthrax, initial antimicrobial therapy should be used intravenously; when fever has subsided to normal, antimicrobial therapy may be switch to oral. The appropriate duration of therapy is a subject for debate. According to most physicians, duration of treatment is 3–5 days for uncomplicated cutaneous anthrax, 10–14 days for systemic anthrax16,19. In the treatment of our cases with malignant pustules, IM procaine penicillin G in 14 patients and oral ciprofloxacin in six patients was used for 7–10 days. Eight patients with malignant edema presentation were treated initially with IV penicillin G for 5 days, followed by IM procaine penicillin G for afterwards 5 days. All strains of B. anthracis isolated from our cases were sensitive to penicillin. In addition, systemic corticosteroids were also used in six patients with malignant edema for the same duration. Toxemic shock, airway obstruction, temporal artery inflammation, deep tissue necrosis and secondary infection, deep scar tissue and eyelid deformity may occur as complications in patients with cutaneous anthrax. Serious complications such as compartment syndrome, meningitis and sepsis can also be seen20–24. In this study, the patients were followed for complications long as it remains in our hospital. Airway obstruction developed in one patient, and eyelid deformity in one patient. Eyelid deformity was reconstructed surgically. In untreated cases of cutaneous anthrax, the mortality rate is about 5–10%. With antimicrobial treatment, this can be reduced to less than 1%16. Sepsis no developed in our patients, all the cases recovered. Anthrax is still a common infectious disease in some regions of Turkey that may cause epidemics. In cutaneous anthrax, though to a lesser extent, life threatening events might be seen. Physicians’ work in that region should be aware in case of sick animal or animal products contact24,25.
Conclusions Cutaneous anthrax must always be kept in mind when characteristic lesions such as a painless ulcer with vesicles, and edema are observed in an individual. Early and correct diagnosis, proper treatment and intervention are life saving factors. Protective precautions as vaccination of animals against anthrax and education of the population would decrease the frequency of the disease.
Declaration of interest The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article.
Cutan Ocul Toxicol, Early Online: 1–4
References 1. Martin GJ, Friedlander AM. Bacillus anthracis (Anthrax). In: Bennett JE, Dolin R, Blaser MJ, eds. Principles and practice of infectious diseases. 8th ed. Philadelphia, PA: Churchill Livingstone; 2015:2391–2409. 2. Doganay M, Metan G, Alp E. A review of cutaneous anthrax and its outcome. J Infect Public Health 2010;3:98–105. 3. Karahocagil MK, Akdeniz N, Akdeniz H, et al. Cutaneous anthrax in eastern Turkey: a review of 85 cases. Clin Exp Dermatol 2008;33:406–411. 4. Kaya A, Tasyaran MA, Erol S, et al. Anthrax in adults and children: a review of 132 cases in Turkey. Eur J Clin Microbiol Infect Dis 2002;21:258–261. 5. Hendricks KA, Wright ME, Shadomy SV, et al. Centers for disease control and prevention expert panel meetings on prevention and treatment of anthrax in adults. Emerg Infect Dis 2014;20. doi: http://dx.doi.org/10.3201/eid2002.130687. 6. Jernigan JA, Stephens DS, Ashford DA, et al. Bioterrorism-related inhalational anthrax: the first 10 cases reported in the United States. Emerg Infect Dis 2001;7:933–944. 7. Goel AK. Anthrax: a disease of biowarfare and public health importance. World J Clin Cases 2015;3:20–33. 8. Pugh AO, Davies JCA. Human anthrax in Zimbabwe. Salisbury Med Bull 1990;68:32–33. 9. Dixon TC, Meselson M, Guillemin J, Hanna PC. Anthrax. N Engl J Med 1999;341:815–826. 10. Rao TN, Venkatachalam K, Ahmed K, et al. A mini-outbreak of cutaneous anthrax in Vizianagaram District, Andhra Pradesh, India. Indian J Dermatol Venereol Leprol 2009;75:416–418. 11. Thappa DM, Karthikeyan K. Cutaneous anthrax: an Indian perspective. Indian J Dermatol Venereol Leprol 2002;68:316–319. 12. Ozden K, Ozkurt Z, Erol S, et al. Cutaneous anthrax patients in Eastern Anatolia, Turkey: a review of 44 adults cases. Turk J Med Sci 2012;42:39–45. 13. Ozkol HU, Karadas S, Sunnetcioglu M, et al. The evaluation of clinical and laboratory findings of 63 inpatient with cutaneous anthrax: characteristics of cutaneous anthrax in Turkey. Turkderm 2014;48:197–203. 14. Ozkurt Z, Parlak M, Tastan R, et al. Anthrax in eastern Turkey, 1992–2004. Emerg Infect Dis 2005;11:1939–1941. 15. Irmak H, Buzgan T, Karahocagil MK, et al. Cutaneous manifestations of anthrax in Eastern Anatolia: a review of 39 cases. Acta Med Okayama 2003;57:235–240. 16. Doganay M. Anthrax. In: Cohen J, Powderly WG, Opal SM, eds. Infectious diseases. 3rd ed. Edinburgh: Mosby; 2010: 1257–1261. 17. Lightfoot NF, Scott RJ, Turnbull PC. Antimicrobial susceptibility of Bacillus anthracis. Salisbury Med Bull 1990;68:95–98. 18. Athamna A, Massalha M, Athamna M, et al. In vitro susceptibility of Bacillus anthracis to various antibacterial agents and their timekill activity. J Antimicrob Chemother 2004;53:247–251. 19. Demirdag K, Ozden M, Saral Y, et al. Cutaneous anthrax in adults: a review of 25 cases in the eastern Anatolian region of Turkey. Infection 2003;31:327–330. 20. Tekin R, Sula B, Deveci O, et al. Cutaneous anthrax in Southeast Anatolia of Turkey. Cutan Ocul Toxicol 2015;34:7–11. 21. Gelaw Y, Asaminew T. Periocular cutaneous anthrax in Jimma Zone, Southwest Ethiopia: a case series. BMC Res Notes 2013;6: 313. 22. Parlak E, Parlak M, Atli SB. Unusual cause of fatal anthrax meningitis. Cutan Ocul Toxicol 2015;34:77–79. 23. Tekin R, Ari S, Dal T, et al. Evaluation of cutaneous palpebral anthrax. Cutan Ocul Toxicol 2013;32:294–298. 24. Parlak E, Aydin A, Parlak M. Cutaneous anthrax cases leading compartment syndrome. J Microbiol Infect Dis 2013;3: 214–217. 25. Gulacti U, Ustun C, Erdogan MO. A small cutaneous anthrax epidemic in Eastern Turkey. J Microbiol Infect Dis 2012;2:9–13.
RESEARCH ARTICLE
Cutaneous anthrax: evaluation of 28 cases in the Eastern Anatolian region of Turkey
Cutaneous and Ocular Toxicology Downloaded from informahealthcare.com by Nyu Medical Center on 07/31/15 For personal use only.
Affan Denk1, Ayse Sagmak Tartar2, Mehmet Ozden1, Betul Demir3, and Ayhan Akbulut1 1
Department of Infectious Diseases and Clinical Microbiology, Faculty of Medicine, Firat University, Elazig, Turkey, 2Department of Infectious Diseases and Clinical Microbiology, Cizre State Hospital, Sirnak, Turkey, and 3Department of Dermatology, Faculty of Medicine, Firat University, Elazig, Turkey Abstract
Keywords
Context: Anthrax is an endemic disease in developing countries. Human cases are usually associated with animal products. About 95% of naturally acquired cases are cutaneous anthrax. Objective: In this study, cutaneous anthrax cases from the Elazig province (the Eastern Anatolian region) of Turkey seen in our hospital within a 6-year period were evaluated with respect to epidemiological and clinical features, diagnosis, treatment and outcome. Methods: Twenty-eight patients with cutaneous anthrax observed between January 2009 and December 2014 were investigated retrospectively. The diagnosis of cutaneous anthrax was based on detailed history, dermatologic findings, including painless, ulcers covered by a characteristic black eschar and/or microbiological procedures, including Gram stain and culture of materials obtained from the lesions. Results: Of the 28 patients followed up with cutaneous anthrax diagnosis, 14 (50%) were female and 14 (50%) were male. The mean age of the cases was 39.6 years (age range 17–65 years). The patients have an incubation period in the range of 1–9 days (mean 4.6 ± 0.5 days). The cases were seen between April and November of each year during the study period. Twenty-three cases (82%) had a history of contact with animals or animal products. Twenty patients (71.4%) showed malignant pustules and eight (28.6%) malignant edema. Bacillus anthracis was isolated in three cases (10.7%) and Gram stain smear were positive in five cases (17.8%). All patients were treated successfully with penicillin or ciprofloxacin. Systemic corticosteroids were added to the antibiotic treatment in six patients with malignant edema. Sepsis no developed in patients, all the cases recovered. Conclusion: Anthrax is still a serious public health problem in Turkey. Cutaneous anthrax must always be kept in mind when characteristic lesions such as a painless ulcer with vesicles, edema, and a history of contact with animals or animal products are observed in an individual. Early and correct diagnosis significantly affects course of the disease. Protective precautions such as vaccination of animals against anthrax and education of the population would reduce the incidence of the disease.
Cutaneous anthrax, endemic disease, outcome, zoonosis
Introduction Anthrax is a zoonotic infectious disease caused by Bacillus anthracis that is an aerobic, Gram-positive, endosporeforming, nonmotile, capsulated, rod-shaped bacterium. In nature, anthrax primarily affects domestic animals such as sheep, goats and cattle1. Humans almost invariably contract the natural disease directly or indirectly from animals or animal products. There are three forms of naturally occurring human anthrax infection; cutaneous, gastrointestinal and inhalational anthrax. Among these clinical forms of anthrax, cutaneous anthrax is most frequent. Cutaneous anthrax typically occurs as a result
Address for correspondence: Dr. Affan Denk, Department of Infectious Diseases and Clinical Microbiology, Faculty of Medicine, Firat University, Elazig 23119, Turkey. E-mail: [email protected]
History Received 5 May 2015 Revised 15 June 2015 Accepted 26 June 2015 Published online 30 July 2015
of exposure to anthrax-infected animals or their products. Cutaneous anthrax could also occur as a result of an aerosol attack2–4. In recent 20 years, B. anthracis come to the fore as potential agent of biological warfare5,6. Anthrax is an infection that prevalence is gradually decreasing in the world. Human anthrax is seen most commonly in Indian Subcontinent, Africa, The Middle East and Latin America. Further, it has also been reported from Zimbabwe, Bangladesh, USA, South Africa, Iraq, Iran and Turkey3,7. The largest outbreak of anthrax known in humans occurred in Zimbabwe, approximately 10 000 cases between 1979 and 1980 leading to 182 deaths8. In developed (industrialized) countries, human anthrax cases are rarely seen9. In the present retrospective study, 28 cases of cutaneous anthrax seen in Firat University Hospital in the Eastern Anatolian region of Turkey between January 2009 and
2
A. Denk et al.
December 2014 were evaluated with respect to epidemiological and clinical features, diagnosis, treatment and outcome.
Cutaneous and Ocular Toxicology Downloaded from informahealthcare.com by Nyu Medical Center on 07/31/15 For personal use only.
Patients and methods The records of 28 cutaneous anthrax cases observed in Firat University Hospital (inpatient the Departments of Infectious Diseases and Dermatology) between January 2009 and December 2014 were examined. Patients were from the Elazig province in the Eastern Anatolian Region of Turkey. The diagnosis of cutaneous anthrax was based on detailed history, dermatologic findings, including painless ulcers covered by a characteristic black eschar and/or microbiological procedures, including Gram stain and culture of materials obtained from the lesions. Self-reported source of infection was determined from categorical responses that included butchering/slaughtering cattle, handling/preparing meat, exposure to a sick animal or to contaminated animal products, exposure to an insect bite and unknown. Age, sex, occupation, the time of onset of the first lesion, antimicrobial therapy received prior to admission, localization, and type of lesions, clinical history, antibiotic treatment, duration of therapy, and outcome were recorded. Samples such as vesicular or bullous fluid taken from the lesions were cultured on 5% sheep blood agar. In addition, blood samples were cultured in an automated blood culture system (Becton Dickinson, Franklin Lakes, NJ) in some patients with fever. Bacillus anthracis was identified by traditional microbiological methods, and also confirmed using Vitek 2 (BioMerieux, Marcy l’Etoile, France) automated identification system. Large white to gray nonhemolytic colonies with irregularly tapered outgrowths were evaluated. Gram stain showed rod-shaped bacteria growing as long chains.
Cutan Ocul Toxicol, Early Online: 1–4
Table 1. The age and gender distribution of the cases. Age range
Female
Male
Total
519 20–29 30–39 40–49 50–59 460 Total (%)
0 0 6 2 3 3 14 (50)
1 6 3 3 0 1 14 (50)
1 6 9 5 3 4 28 (100)
Figure 1. The distribution of cases according to months.
Results Of the 28 patients followed up with cutaneous anthrax diagnosis, 14 (50%) were female and 14 (50%) were male. The mean age of the cases was 39.6 ± 12.6 years (age range 17–65 years). More than half of the cases were in the agegroups 20–29 and 30–39 years. The age and gender distribution of the cases are shown in Table 1. The cases were seen between April and November of each year during the study period, August (28.5%) and September (28.5%) were the most intensive months (Figure 1). Twenty-three cases (82%) had a history of contact with sick cows or sheep, animal slaughtering, skin peeling, meat processing or helping in one of these activities. Three of these cases were butcher. Five cases (18%) did not any history of contact with animals or animal products. The patients have an incubation period in the range of 1–9 days (mean 4.6 ± 0.5 days). All cases in our study were cutaneous anthrax; 20 (71.4%) patients showed malignant pustules located on the hands/fingers and arms. Eight (28.6%) patients exhibited with malignant edema with lesions located on the face/neck and arms (Figures 2 and 3). Localization of the lesions in the 28 cases is given in Table 2. Bacillus anthracis was isolated from vesicular/bullous fluid cultures in three cases (10.7%) and Gram stain smear
Figure 2. Malignant pustule. A characteristic necrotic lesion surrounded by blisters and edema on the left hand.
were positive for Gram-positive rods of B. anthracis in five cases (17.8%). Culture and Gram stain smear were both positive in three (10.7%) of these cases. Blood cultures taken for all patients with fever were negative. Seventeen patients
Cutaneous anthrax
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DOI: 10.3109/15569527.2015.1067818
Figure 3. Malignant edema. Lesions on the right and left eyelids are accompanied by swelling of the lips and face. Table 2. Localization of skin lesions in the cases. Localization of skin lesions
No. (%)
Hands and fingers Wrists and arms Eyelids and face Neck Total
18 6 3 1 28
(64.3) (21.4) (10.7) (3.6) (100)
(60.7%) had received an antibiotic before admission to our hospital. Bacillus anthracis was not demonstrated in Gram stain smear or culture taken from the lesions in these 17 patients. All of the patients were treated successfully with penicillin or ciprofloxacin. In the treatment of patients with malignant pustules, procaine penicillin G (2 800 000 IU/day) in 14 patients and oral ciprofloxacin (2 750 mg/day) in six patients was used for 7–10 days. Eight patients with malignant edema presentation were treated initially with intravenous penicillin G (8 3 million IU/day) for 5 days, followed by intramuscular procaine penicillin (2 800 000 IU/day) for afterwards 5 days. Systemic corticosteroids (i.v. methyl prednisolone 1–2 mg/kg/day or i.v. dexamethasone 32 mg/day) were added to the antibiotic treatment in six patients with malignant edema. Sepsis no developed in patients, all the cases recovered.
Discussion Human anthrax is not a major problem of health in developed countries as only a few encounters are reported from such countries, but especially cutaneous anthrax is still a serious public health problem in developing countries like Turkey whose economy is principally agriculture dependent and
3
livestock is common2–4,10. Cutaneous anthrax accounts for approximately 95% of all reported human anthrax cases. It is known that anthrax has been for a long time in the Eastern Anatolia Region of Turkey where animal husbandry is the prime occupation. In Turkey, most of the anthrax cases (almost all) are in the cutaneous form2,3. The disease occurred about equally in women and men, in animal husbandry in rural areas4. In this study, there was no relationship between genders. Most of our cases were in 20–29 and 30–39 years according to the age-groups. People are exposed to infectious agent during transactions, such as butchering/slaughtering of the animal, processing/handling meat, cutting of meat and skinning2–4. In 23 our cases (82%), there was a history of direct or indirect contact by infected animal or animal products. The disease is generally reported in summer and autumn months11–13. In our study, cases occurred between April and November (the most frequent in August and September), because of animal slaughtering, meat cutting and meat roasting are usually realized. Anthrax cases no seen between December and March of each year during the study period. Cutaneous anthrax develops on exposed skin sites following a minor abrasion. Areas of exposed skin like hands, arms, face and neck were mostly affected14,15. Twenty (71.4%) patients exhibited malignant pustules located on the hands/ fingers and arms. Eight (28.6%) patients exhibited with malignant edema with lesions located on the face/neck and arms. Diagnosis of cutaneous anthrax first requires suspicion. In non-endemic areas, diagnosis may be difficult. If a patient has a typical painless pustule or extensive edema and a contact history with domestic animal, the diagnosis may be easy. The diagnosis is confirmed by detecting the agent microorganism in Gram stain or isolation of B. anthracis in the culture. Today, in addition to these, serological and molecular methods such as enzyme linked immunosorbent assay and polymerase chain reaction have been used5,12. The rate of positive anthrax cultures in the skin lesions does not exceed 60–65%9. After 24–48 h of the use of a potent antibiotic against B. anthracis, possibility of the growth of the microorganism in the cutaneous lesion has decreased2. In this study, in three cases (10.7%) material obtained from the lesion was culture positive. The majority of cases had been treated with antimicrobials before being admitted to our hospital. Seventeen cases (60.7%) had a history of antimicrobial use before admission to our hospital and B. anthracis was not demonstrated in Gram stain smear or culture taken from the lesions in these 17 patients. Three of 11 (27.2%) who had not taken antimicrobials were culture positive. Although these patients reported else, we suspect that some of their might have taken antimicrobials prior to admission. It is known that antimicrobials can be provided without prescription in our country. Diagnosis in all culture negative patients was made through history and physical examination. Penicillins, quinolones, tetracyclines, macrolides, aminoglycosides, carbapenems, rifampicin, vancomycin, clindamycin, chloramphenicol, linezolid, cefazolin and other first-generation cephalosporins are effective against in vitro human clinical isolates of B. anthracis. Topical therapy is not useful16–19. The recommended treatment of naturally
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A. Denk et al.
occurring cutaneous anthrax is generally first choice procaine penicillin G (0.6–1.2 million IU IM every 12–24 h) or benzyl penicillin G (4 mU IV every 4–6 h) or amoxicillin (500 mg oral every 6–8 h), alternatively ciprofloxacin (500–750 mg oral every 12 h, 200–400 mg IV every 12 h) or doxycycline (100 mg oral every 12 h). Antimicrobial therapy should be used orally in mild cutaneous anthrax. In cases of severe cutaneous anthrax or systemic anthrax, initial antimicrobial therapy should be used intravenously; when fever has subsided to normal, antimicrobial therapy may be switch to oral. The appropriate duration of therapy is a subject for debate. According to most physicians, duration of treatment is 3–5 days for uncomplicated cutaneous anthrax, 10–14 days for systemic anthrax16,19. In the treatment of our cases with malignant pustules, IM procaine penicillin G in 14 patients and oral ciprofloxacin in six patients was used for 7–10 days. Eight patients with malignant edema presentation were treated initially with IV penicillin G for 5 days, followed by IM procaine penicillin G for afterwards 5 days. All strains of B. anthracis isolated from our cases were sensitive to penicillin. In addition, systemic corticosteroids were also used in six patients with malignant edema for the same duration. Toxemic shock, airway obstruction, temporal artery inflammation, deep tissue necrosis and secondary infection, deep scar tissue and eyelid deformity may occur as complications in patients with cutaneous anthrax. Serious complications such as compartment syndrome, meningitis and sepsis can also be seen20–24. In this study, the patients were followed for complications long as it remains in our hospital. Airway obstruction developed in one patient, and eyelid deformity in one patient. Eyelid deformity was reconstructed surgically. In untreated cases of cutaneous anthrax, the mortality rate is about 5–10%. With antimicrobial treatment, this can be reduced to less than 1%16. Sepsis no developed in our patients, all the cases recovered. Anthrax is still a common infectious disease in some regions of Turkey that may cause epidemics. In cutaneous anthrax, though to a lesser extent, life threatening events might be seen. Physicians’ work in that region should be aware in case of sick animal or animal products contact24,25.
Conclusions Cutaneous anthrax must always be kept in mind when characteristic lesions such as a painless ulcer with vesicles, and edema are observed in an individual. Early and correct diagnosis, proper treatment and intervention are life saving factors. Protective precautions as vaccination of animals against anthrax and education of the population would decrease the frequency of the disease.
Declaration of interest The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article.
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