A Woman with Persistent Fever and a Skin Lesion

CLINICAL

A woman with persistent fever and a skin lesion

Keen S Tai, Esha D Gupta other viral infections, typhoid fever and Answer 3 leptospirosis may be considered, given the patient’s travel history. Scrub typhus is one of the rickettsioses and is caused by the Gram-negative CASE organism Orientia tsutsugamushi.1 It occurs CASE CONTINUED A previously well Malaysian woman aged in Central and Southeast Asia, the Pacific 52 years was referred for fever, headache, Investigation results were: and Indian Ocean Islands, and northern myalgia, anorexia and malaise of one • haemoglobin: 12.8 g/dL, white cell Australia, where it is recognised to occur week duration. She had participated in a count: 3700 (N70% L25%), in rainforests.2,3 Travellers are at risk of cross-country hike in Selangor, Malaysia, platelets: 145 × 109/L acquiring this infection. about two weeks before the onset of her • aspartate aminotransferase (AST) The mode of transmission is through illness. This included trekking across an 75 IU/L, alanine aminotransferase the bite of larval-stage trombiculid mites oil palm plantation. On examination, (ALT) 98 IU/L (Leptotrombidium spp.; also referred to as she had a temperature of 38.1°C, and a • positive immunoperoxidase testing of ‘chiggers’) infected with O. tsutsugamushi. lesion was found near the left popliteal immunoglobulin M (IgM) for Orientia An eschar develops at the bite site.4 fossa (Figure 1). There was tender tsutsugamushi (1:400). Trombiculid mites are found in areas lymphadenopathy in the left inguinal area. The patient was diagnosed with scrub of dense scrub and vegetation. Their life typhus and treated with oral doxycycline cycle consists of egg, larval, nymphal and 100 mg twice daily for a week. Fever and adult stages. Adults and nymphs live in the Question 1 symptoms resolved, and recovery was soil and feed on plants, but larval forms uncomplicated. may bite animals such as rodents or mice; What are the differential diagnoses humans may be incidental victims. Mites for this lesion? are small (0.2–0.4 mm) and are usually 4 Question 3 only visible under magnification. Question 2 What is scrub typhus? How is it Answer 4 What investigations are indicated? transmitted? The incubation period is approximately Answer 1 Question 4 10 days but may vary from six to 21 days and presents with fever, chills, headache, Figure 1 shows a raised erythematous What are the clinical features of nausea, vomiting, conjunctivitis and lesion with a dark central necrotic area. scrub typhus? The differential diagnoses include: • an eschar that may be due to a Question 5 rickettsial infection • cutaneous anthrax In what other conditions may • tularemia eschars be found? • ecthyma due to various bacterial infections, fungal infections, trauma or Question 6 spider bites. What investigations are used to Answer 2 diagnose scrub typhus?

In addition to screening for the Question 7 infections listed above, blood cultures Figure 1. Skin lesion near left popliteal fossa and investigations for dengue fever and What are the treatment options?

myalgia.5,6 A macular rash involving the and indirect immunoperoxidase assays Provenance and peer review: Not commissioned, externally peer reviewed. trunk and limbs may develop towards the showing rising titres of IgM antibodies end of the first week. Lymphadenopathy against O. tsutsugamushi.8,9 Polymerase References and splenomegaly may occur. chain reaction can be performed on 1. Cowan G. Rickettsial diseases: The typhus Patients with more severe disease may blood and tissue specimens. group of fevers – A review. Postgrad Med J develop delirium, jaundice, pneumonitis, 2000;76(895):269–72. meningoencephalitis, myocarditis, 2. Nachega JB, Bottieau E, Zech F, Van Gompel A. Answer 7 Travel-acquired scrub typhus: Emphasis on the multi-organ failure and disseminated differential diagnosis, treatment and prevention intravascular coagulation. Doxycycline orally, or intravenously strategies. J Travel Med 2007;14(5):352–55. Eschars appear as raised erythematous for those with more severe disease, is 3. Currie B, Lo D, Marks P, Lum G, Whelan P, 2,6,10 Krause V. Fatal scrub typhus from Litchfield papules with dark central necrotic areas. the drug of choice in scrub typhus. Park, Northern Territory. Comm Dis Intell They often occur in warm, damp and Treatment should be continued for a 1996;20:420–21. covered areas of the body such as the chest week to prevent relapse. Alternative drugs 4. Kundavaram AP, Jonathan AJ, Nathaniel SD, and inframammary area, abdomen, axilla, are azithromycin, telithromycin and Varghese GM. Eschar in scrub typhus: A valuable clue to the diagnosis. J Postgrad Med groin and genitalia and may be missed rifampicin. Azithromycin is considered 2013;59(3):177–78. on clinical examination.4 The eschar is safe in pregnancy. 5. Rajapakse S, Weeratunga P, Sivayoganathan painless, and the patient may be unaware There is currently no vaccine available. S, Fernando SD. Clinical manifestations of scrub typhus. Trans R Soc Trop Med Hyg of it, although it can sometimes be pruritic. 2017;111(2):43–54. doi: 10.1093/trstmh/trx017. Eschars heal in 3–4 weeks, sometimes with Key points 6. Peter JV, Sudarsan TI, Prakash JAJ, Varghese GM. scarring and pigmentation. Severe scrub typhus infection: Clinical features, diagnostic challenges and management. World Common laboratory findings in cases • Scrub typhus should be considered in J Crit Care Med 2015;4(3):244–50. doi: 10.5492/ of scrub typhus include leukopenia, patients with persistent fever and a wjccm.v4.i3.244. thrombocytopenia and elevated liver history of travel to an endemic area. 7. Taylor AJ, Paris DH, Newton PN. A systematic transaminases.2 In the presence of an eschar, review of mortality of untreated scrub typhus • (orientia tsutsugamushi). PloS Negl Trop Untreated scrub typhus has significant appropriate antibiotics for scrub typhus Dis 2015;9(8):e0003971. doi: 10.1371/journal. morbidity and mortality rates. A meta- may be commenced while awaiting pntd.0003971. analysis of untreated scrub typhus found a investigative results. 8. La Scola B, Raoult D. Laboratory diagnosis of rickettsioses: Current approaches to diagnosis of median duration of fever of 14.4 days and • Travellers at risk should be advised on old and new rickettsial diseases. J Clin Micriobiol a median mortality of 6%.7 preventive measures against tick bites, 1997;35(11):2715–27. such as wearing protective clothing 9. Koh GC, Maude RJ, Paris DH, Newton PN, Blacksell SD. Diagnosis of scrub typhus. Am J Answer 5 and using insect repellents, and should Trop Med Hyg 2010;82(3):368–70. doi: 10.4269/ avoid walking barefoot and sitting or ajtmh.2010.09-0233. Eschars may be found in other acute lying on bare ground. 10. Kim DM, Yu KD, Lee JH, Kim HK, Lee SH. infections, and some differentiating Controlled trial of a 5-day course of telithromycin versus doxycycline for treatment of mild to clinical features of these conditions are Authors moderate scrub typhus. Antimicrob Agents Chemother 2007;51(6):2011–15. summarised in Table 1. Keen S Tai BSc, MBBS, FRCP, Senior Lecturer, Department of Internal Medicine, International 11. Doganay M, Metan G, Emine A. A review of Medical University, Seremban Campus, Malaysia. cutaneous anthrax and its outcome. J Infect Answer 6 [email protected] Public Health 2010;3(3):98–105. doi: https://doi. Esha D Gupta MBBS, FRCPI, FRCP, Professor org/10.1016/j.jiph.2010.07.004. Scrub typhus may be diagnosed with of Medicine, Department of Internal Medicine, 12. Eliasson H, Broman T, Forsman M, Bäck International Medical University, Seremban E. Tularemia: Current epidemiology and serological investigations such as Campus, Malaysia disease management. Infect Dis Clin Am indirect immunofluorescence antibody Competing interests: None. 2006;20(2):289–311, ix.

Table 1. Differential diagnoses for eschars

Disease Organism Background Features of eschar

Cutaneous anthrax11 Bacillus anthracis Contact with animals or animal products Often found in exposed areas such contaminated with spores of B. anthracis as hands, wrists, arms, face and neck Population at risk includes those in the May have surrounding blistering, agricultural industry haemorrhage and oedema

Tularemia12 Francisella tularensis Found in the northern parts of North Often found on hands, upper and lower limbs. America, Europe and Asia Associated with regional lymphadenopathy Spread by ticks or deerfly bites or direct contact with infected animals or meat