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| REVIEW ARTICLE |
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| Year : 2019 | Volume
: 17
| Issue : 4 | Page : 134-137 |
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Eschar: A vital clue for diagnosis of scrub typhus
Kundavaram Paul Prabhakar Abhilash, Karthik Gunasekaran
Department of Emergency Medicine, Christian Medical College, Vellore, Tamil Nadu, India
| Date of Submission | 27-Oct-2019 |
| Date of Decision | 18-Nov-2019 |
| Date of Acceptance | 26-Nov-2019 |
| Date of Web Publication | 12-Dec-2019 |
Correspondence Address:
Dr. Kundavaram Paul Prabhakar Abhilash
Department of Emergency Medicine, Christian Medical College, Vellore - 632 004, Tamil Nadu
India
 Source of Support: None, Conflict of Interest: None  | Check |
DOI: 10.4103/cmi.cmi_53_19
The most pathognomonic sign of scrub typhus is the presence of an eschar, which represents the site of inoculation, where initial multiplication occurs before widespread dissemination. Transmission electron microscopy analysis of an eschar shows detectable Orientia tsutsugamushi in outermost layers of the perifocal inflamed skin and not in the central necrotic zone, which consists of dried skin layers only. The presence of eschar in a patient with scrub typhus varies widely in different studies from 9.5% to 86% of patients with higher values reported from the Orient. A characteristic difference is noted in the distribution of eschars over the body in both the sexes. In females, the chest (inframammary area) and abdomen are the most common sites of an eschar, while the axilla, groin, and genitalia are the most common sites of eschar in males. A thorough physical examination, especially of the hidden areas such as the genitalia, scalp, and postaural areas, is imperative in identifying this vital diagnostic clue of scrub typhus.
Keywords: Eschar, Orientia tsutsugamushi, rickettsial infection, scrub typhus
How to cite this article:
Abhilash KP, Gunasekaran K. Eschar: A vital clue for diagnosis of scrub typhus. Curr Med Issues 2019;17:134-7 |
| Introduction | |  |
Scrub typhus is a vector-borne infection caused by the Gram-negative bacteria, Orientiatsutsugamushi. It is transmitted to humans by infected larva of trombiculid mites (Leptotrombidium deliense and Leptotrombidium akamushi). It is the most common re-emerging rickettsial infection in India and many other Southeast Asian countries. Although the disease is similar in clinical presentation to other forms of typhus, O.tsutsugamushi is no longer classified in the genus Rickettsia and is currently recognized as a Gram-negative bacterium. It is a zoonotic disease and is widely prevalent in areas with heavy monsoon and an agrarian way of life. Approximately one million cases occur each year with more than a billion people being at risk of disease.[1]
| History of Scrub Typhus | | |
Gram-negative bacteria were first identified in 1930 in Japan. Several epidemics of this infection were reported among the troops of the World War II (WWII) in Myanmar and Sri Lanka and also in the Pacific Islands, where it was associated with very high mortality as there was no known antibiotic to it at that time.[2],[3] The disease was also very problematic for the US troops stationed in Japan after WWII and was variously known as “Shichitō fever” or “Hatsuka fever.”[4]
| Geographic Distribution and Epidemiology | | |
Scrub typhus is commonly seen in the geographic area known as “tsutsugamushi triangle,” which extends from Northern Japan and Far East Russia in the north, to territories around the Solomon sea in Northern Australia in the south, and to Pakistan and Afghanistan in the west.[5],[6] The countries with the highest incidence of scrub typhus are China, Japan, Indonesia, Malaysia, Thailand, Pakistan, Korea, Northern Australia, and the Pacific Islands.[6],[7] However, recent evidence shows that this infection may not be strictly restricted to the tsutsugamushi triangle. From the 1950s, there have been sporadic reports from East Africa.[8],[9],[10] In the 1900s, there were confirmed reports of scrub typhus in Africa, and in the 21st century, cases were reported from South America, especially Peru and Chile.[10],[11],[12],[13],[14],[15]
It is seen in most parts of India, especially in the Eastern and Western Ghats in the south; Tamil Nadu, Andhra Pradesh, Kerala, Maharashtra, Rajasthan, Himachal Pradesh, Vindhyachal, and Satpura Ranges in Central India; and the Himalayan belt in the north and the northeastern states.[16],[17],[18],[19],[20]
| Eschar of Scrub Typhus | | |
The usual presentation is that of short duration fever, headache, myalgia, and varying involvement of the major organs. O.tsutsugamushi infects the endothelium of the small blood vessels causing disseminated immune-mediated lymphohistiocytic vasculitic illness, resulting in severe complications such as acute respiratory distress syndrome (ARDS), hepatitis, renal failure, meningoencephalitis, and myocarditis with shock in a varying proportion of patients.[19]
The most pathognomonic sign of scrub typhus is the presence of an eschar, which is variously described as a black-crusted lesion or a cigarette burn-like lesion or a black necrotic lesion.[21],[22] The eschar represents the site of inoculation, where initial multiplication occurs before widespread dissemination. It is formed when the chigger mite, which is very small (0.2–0.4 mm) and can only be seen through a microscope or magnifying glass, crawls up the body and feeds on human skin, usually in warm, damp areas and places where pressure from clothing occurs. The trombiculid mites proceed through the following stages of life: Egg, larva, nymph, and adults. Adults and nymphs live in the vegetation and moist soil and feed on plants, small insects, and insect eggs. The larvae, commonly referred to as “chiggers,” may bite animals or humans that come into contact with them. O.tsutsugamushi parasitized these mites and is transmitted to human beings when the chiggers bite them. The bacteria inoculated during the bite multiply at the inoculation site with the formation of a papule. The papule slowly ulcerates and becomes necrotic, evolving into a characteristic eschar, with or without regional lymphadenopathy.
Eschar is usually 5–15 mm long and is typically painless and nonpruritic, and hence, its presence is not reported by patients.[23] When mature, these lesions consist of an innermost black crust, an erythematous patch in the middle, and a thin surface skin layer that is outlined by white scales. Eschars are detectable within 6–8 days of infection. After maturation, the crust and overlying scales slowly disappear. The eschar is sloughed off approximately 2 weeks after symptom onset.[23],[24]
| Evolution of an Eschar | | |
The evolution of a classic eschar was described in detail by Park et al. by dermoscopy and routine photography.[23] In the early stages, a central vesicle appears which is usually surrounded by erythema and sometimes by whitish scales. With progression of the lesion, i.e., 3 days from symptom onset, a typical black necrotic crust appears at the center with surrounding erythema and scales becoming more prominent. The typical eschar commonly noticed is formed 6–8 days after symptom onset. After the 1st week, the necrotic black crust slowly becomes smaller with decreasing erythema and diminishing surrounding scales. In the 3rd week of illness, the crust completely disappears, leaving behind only a whitish scar-like macule as a result of fibrosis. The surrounding erythema eventually converts into red–brown-colored hyperpigmentation.
O. tsutsugamushi invades dermal cells and infects antigen-presenting cells in the subepidermis, basal epidermis, and superficial dermis.[24] The dry eschar core consists of thick layers of compressed epidermis and dermis, with necrosis of the overlying epidermis. Transmission electron microscopy analysis of an eschar shows detectable O. tsutsugamushi in outermost layers of the perifocal inflamed skin and not in the central necrotic zone, which consists of dried skin layers only.[24],[25] The eschar is not the main site of O. tsutsugamushi replication, and hence, it is likely that the bacterial load in the eschar decreases over time.
Orientia species have a unique transmembrane protein, a 56-kDa type-specific antigen (TSA), which is likely involved in adherence to and invasion of target cells. The presence of this unique TSA is mainly responsible for its exclusion from the Rickettsia genus. Initially, complement fixation-based serologic testing was based largely on this protein, to identify the original Gilliam, Karp, and Kato “prototype” strains. Since then, more than 20 unique types have been identified and arranged into “clusters,” initially using further serologic testing and then the genetic sequences of this unique protein. Diagnostically, using polymerase chain reaction (PCR) to look for the 56-kDa protein gene in an eschar is an efficient method in the early stages of illness. Varghese et al. performed PCR genotypic analysis on eschar samples among patients presenting with scrub typhus in Tamil Nadu, South India.[26],[27] On phylogenetic and sequence analysis, 65% of the strains clustered with the Kato group, 35% clustered with Karp-like isolates, and one with the Gilliam stain.[26],[27] Varghese et al.'s study using PCR from eschars from South India showed a predominance of Kato-like strains, from all three regions studied.[27],[28]
| Location of Eschar | | |
A pathognomonic eschar is a typical feature of scrub typhus and is of high diagnostic value. Presence of eschar is an important finding for the diagnosis of scrub typhus, rickettsialpox, and other mite- or tick-borne rickettsiosis. The presence of eschar in a patient with scrub typhus varies widely in different studies from 9.5% to 86% of patients, with higher values reported from the Orient as shown in [Table 1].[16],[17],[19],[20],[21],[22] This difference is perhaps related to the skin complexion with a dark and erythematous eschar easily visible and identified in fair-skinned individuals and does not necessarily reflect the presence or absence of eschar in the study cohort. Studies from Vellore in Tamil Nadu showed eschar pick up rates of 45%–56%.[18],[19],[25] Vivekanandan et al. found an incidence of 46% which is lesser than the 75.6% incidence reported by Inamdar et al. from hospitals near the same geographic location.[16],[29] Sirisanthana et al. from Thailand and Kim et al. from Korea reported eschar incidences of 68% and 85.5%, respectively.[30],[31]
Common sites include the abdomen, genitalia, axillary folds, and the chest. A characteristic difference is noted in the distribution of eschars over the body in males and females.[21],[31] In females, the chest (inframammary area) and abdomen (42.3%) are the most common sites of an eschar, while the axilla, groin, and genitalia (55.8%) are the most common sites of eschar in males.[21] However, eschars may be found in unusual but obvious sites such as the eyebrows and the lips and still be missed on initial examination.[32] A thorough physical examination, especially of the hidden areas such as the genitalia, buttock folds, scalp, and postaural areas, is imperative in identifying this value diagnostic clue of scrub typhus.
Does the presence of an eschar correlate with the severity of scrub typhus infection? This question has been answered through a few studies, and there has been no clinical correlation between the two.[33] Shaikh et al. showed that patients with eschar had a higher incidence of renal failure, respiratory system involvement, and cardiovascular system involvement.[31] Patients with an eschar had significantly higher requirement for noninvasive ventilation (9.1% vs. 1.9%; P = 0.04).[33] It would be interesting to see if the location of eschar predisposes to certain organ involvement; e.g. eschar on the chest and ARDS. It was earlier thought that a higher inoculum load of O.tsutsugamushi correlates directly with the presence of an eschar, thus resulting in more severe disease. However, Kim et al. showed the contrary in that patients with an eschar are probably identified earlier with prompt treatment initiated earlier and hence have milder disease.[31]
Scrub typhus is a great mimicker due to multisystem involvement and a myriad of presentations simulating many other common conditions. Many unusual presentations with meningitis, acute abdomen, pancreatitis, and splenic infarcts have been described.[34],[35],[36],[37],[38] This complex and unusual presentations may confuse clinicians and mislead them easily. Scrub typhus is also associated with many serious complications and has a mortality rate of 14%–20%.[18],[19],[28],[39],[40] Hence, the importance of thorough clinical examination and identification of the pathognomonic eschar that would clinch the diagnosis cannot be emphasized more.
Despite extensive research at the molecular level, certain lacunae in knowledge still exist. Further research can be focused on molecular phenotyping, genomic analysis of O. tsutsugamushi, and culturing the organism from biopsies of an eschar.
| Conclusion | | |
The pathognomonic eschar of scrub typhus, which is usually found on the genitalia, abdomen, chest, and axillary folds, is one of the most valuable clues in the diagnosis. Clinicians should be aware of the evolving form of an eschar throughout the illness and promptly identify it to make an accurate diagnosis of scrub typhus.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interes
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[Table 1]
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