A case of acute pulmonary edema in scrub typhus: a rare complication with normal cardiac and renal function

Abstract

Background

Scrub typhus is a mite-borne rickettsial infection endemic to parts of Asia, including Sri Lanka, with a wide range of clinical manifestations.

Case presentation

We report a rare case of a 16-year-old male who presented with a seven-day febrile illness complicated by hypoxemia and pulmonary congestion. Clinical examination revealed an eschar and inguinal lymphadenopathy, raising strong suspicion of scrub typhus, which was subsequently confirmed by a Weil-Felix OXK titer of 1:1280. Despite initial suspicion of myocarditis, cardiac and renal evaluations were normal, and the patient rapidly improved with doxycycline and low-dose frusemide. The clinical course, absence of organ dysfunction, and prompt radiological resolution supported a diagnosis of noncardiogenic pulmonary edema. ARDS was considered unlikely and was ruled out.

Conclusion

This case highlights scrub typhus as a rare cause of pulmonary edema occurring in the absence of cardiac and renal involvement, underscoring the need for clinical awareness in endemic regions.

Clinical trial number

Not applicable.

Background

Scrub typhus, caused by Orientia tsutsugamushi, is a mite-borne rickettsial infection endemic to the Asia-Pacific region, including Sri Lanka [1, 2]. It is transmitted to humans through the bite of larval trombiculid mites (“chiggers”) [2]. A study from northern Sri Lanka reported that 84.4% of patients with clinical features of rickettsial illness were seropositive for scrub typhus, with most exhibiting a characteristic eschar [3]. Scrub typhus can present with a wide clinical spectrum, from asymptomatic infection to severe illness involving multiorgan dysfunction, shock, and even fatal outcomes [4]. Pleuropulmonary involvement in scrub typhus has been well documented in the literature, with reported manifestations including pleural effusion, pneumonia, interstitial pneumonitis, and acute respiratory distress syndrome (ARDS) [5]. In scrub typhus, cardiac dysfunction is recognized to contribute to the development of pulmonary edema [6]. However, acute pulmonary edema in the absence of overt cardiac or renal pathology is an exceedingly rare presentation.

We present a rare case of scrub typhus in a previously healthy adolescent male who developed acute pulmonary edema without evidence of myocarditis or renal impairment. This case highlights the importance of early recognition of atypical respiratory complications of scrub typhus and the need for a high index of suspicion in endemic regions.

Case presentation

A 16-year-old male was transferred from a local hospital for further management of a febrile illness lasting seven days, that was complicated by respiratory distress. His illness began with a continuous high-grade fever associated with chills, rigors, headache, and body aches. There were no focal symptoms such as productive cough, urinary symptoms, or diarrhea. He sought outpatient care on day 2, but symptoms persisted. By day five, his fever remained unresolved, and he developed a poor appetite, vomiting, and reduced oral intake, prompting admission to a local hospital. He was started on 625 mg of oral coamoxiclav every 8 h.

On day six at the local hospital, he developed a marginally low blood pressure of 88/56 mmHg and was treated with an intravenous saline bolus, which improved his BP to 98/60 mmHg. Despite the low reading, his mean arterial pressure was > 65 mmHg, with warm peripheries, and adequate urine output, indicating that he was not in shock. However, later that night, he developed respiratory distress with an SpO₂ of 88%, leading to his transfer to our District General Hospital. On arrival, the patient appeared ill, with a respiratory rate of 24 breaths/min and an SpO₂ of 89% on room air. Auscultation revealed few bilateral basal crepitations, but there was no elevated JVP or pedal edema. His vital signs were relatively stable, with a blood pressure of 102/60 mmHg and a heart rate of 134 bpm. On detailed examination, an eschar was found on the right buttock, leading to a clinical diagnosis of scrub typhus (Fig. 1). He also had right inguinal lymphadenopathy, further supporting the diagnosis. He did not have hepatomegaly or splenomegaly on examination. He was promptly started on 200 mg of oral doxycycline.

Fig. 1.

Eschar on the right buttock in this patient with scrub typhus, with the scab accidentally removed, serving as a key diagnostic clue

Given his respiratory distress, the initial differentials included scrub typhus myocarditis with cardiogenic pulmonary edema and scrub typhus pneumonitis. A bedside ultrasound scan of the chest revealed bilateral mild pleural effusions with significant B-lines, suggesting pulmonary interstitial involvement, but there was no consolidation. Bedside echocardiography performed by the emergency team revealed mild global hypokinesia, whereas electrocardiogram revealed sinus tachycardia without abnormal T or ST changes or arrhythmias (Fig. 2). His chest X-ray revealed upward diversion of pulmonary vessels, and bilateral pulmonary hilar congestion with a bat-wing appearance suggestive of pulmonary edema (Fig. 3A). Arterial blood gas analysis on room air revealed pH 7.5, pCO₂ 27.2 mmHg, pO₂ 57 mmHg, and HCO₃⁻ 21 mmol/L, corresponding to PaO₂/FiO₂ ratio of 271.4. A working diagnosis of scrub typhus-associated myocarditis with pulmonary edema was made, and the patient was given oxygen via a face mask and intravenous frusemide 20 mg. Within three hours, his respiratory distress improved, his SpO₂ increased to 96% on room air, his respiratory rate normalized to 18 breaths/min, and his heart rate decreased to 102 bpm. However, a formal cardiology echocardiogram later revealed normal left ventricular function with no evidence of myocarditis, and troponin levels were within normal limits, making cardiogenic pulmonary edema unlikely. Given his good urine output and normal serum creatinine levels, renal failure as a contributing factor was also ruled out. Although BNP was unavailable, the diagnosis of noncardiogenic pulmonary edema was made on the basis of the remaining clinical evidence. The results of the patient’s blood tests are summarized in Table 1.

Fig. 2.

Electrocardiogram of this patient showing sinus tachycardia without abnormal T or ST changes or arrhythmias

Fig. 3.

Serial chest X-rays of this patient with scrub typhus. (A) Initial radiograph showing upward diversion of pulmonary vessels, bilateral hilar congestion with bat-wing appearance, suggestive of pulmonary edema. (B) Follow-up imaging after 48 h

Table 1.

Summary of the laboratory test results of the patient

Laboratory test	Result	Normal range
White cell count	4.07 × 109/L	4.0–10.0 × 109/L
Hemoglobin	12.1 g/dL	12–15 g/dL
Platelets	76 × 109/L	150–400 × 109/L
C-Reactive protein	91 mg/L	0–3 mg/L
Aspartate transferase	95.5 U/L	15–37 U/L
Alanine aminotransferase	119.4 U/L	16–63 U/L
Sodium	137 mmol/L	136–145 mmol/L
Potassium	3.94 mmol/L	3.5–5.1 mmol/L
Creatinine	0.81 mg/dL	0.7–1.3 mg/dL
Urea	23.3 mg/dL	18–55 mg/dL
Prothrombin time	13.4 s	11–13.5 s
Serum albumin	3.7 g/dL	3.5–5.2 g/dL

His diuretic therapy was continued for 48 h before discontinuation. Doxycycline was continued at 200 mg every 12 h for 48 h, followed by 100 mg every 12 h for the next eight days. He was monitored in the intensive care unit for 24 h before being transferred to the medical ward. His fever resolved within 36 h of admission. A repeat chest X-ray performed after 48 h of diuretic therapy showed significant improvement (Fig. 3B). He made an uneventful recovery before being discharged in stable condition. The Weil-Felix test result, which is not immediately available due to processing time, was received two weeks after presentation and revealed a high OXK titer of 1:1280, supporting the diagnosis of scrub typhus.

Discussion

Orientia tsutsugamushi, is an obligate intracellular gram-negative bacterium transmitted by the bite of infected chigger larvae of Leptotrombidium mites [2]. Following inoculation, the bacteria replicate locally, leading to the development of a papule that subsequently ulcerates and forms a necrotic eschar. One of the earliest and most characteristic clinical signs of scrub typhus is eschar. While its presence is highly suggestive of scrub typhus, it is often overlooked because of its painless nature and hidden locations, such as the groin, axilla, or buttocks, especially in dark-skinned individuals [2]. In endemic regions such as Sri Lanka, the identification of an eschar remains vital for early diagnosis, as demonstrated in our case. Eschar is often accompanied by regional lymphadenopathy, which can progress to generalized lymph node enlargement within a few days [7]. Humans typically develop an acute febrile illness within 8–10 days following a chigger bite, with bacteraemia preceding the onset of fever by approximately 1–3 days [8]. Like other rickettsial infections, scrub typhus is characterized by perivascular inflammation affecting small blood vessels. Although endothelial cells are involved, histopathological findings suggest the involvement of macrophages in the disease process [9]. Scrub typhus may disseminate into multiple organs via macrophages and shed endothelial cells in the blood stream, resulting in the development of fatal complications [7].

The presence of pleuropulmonary involvement in patients with scrub typhus has been well documented in the literature. The pathophysiology is thought to involve direct infection of the pulmonary endothelium, immune-mediated injury, and systemic inflammatory responses. However, pulmonary edema in the absence of cardiac or renal dysfunction is exceedingly rare. In our patient, the initial suspicion of myocarditis was based on mild global hypokinesia observed via bedside echocardiography. This was later ruled out by formal echocardiographic assessment, which revealed preserved left ventricular function and normal troponin levels. This discrepancy of both echocardiogram assessments was most likely due to technical limitations of the bedside assessment rather than true transient dysfunction. BNP measurement, which can help differentiate cardiogenic from noncardiogenic pulmonary edema, was not available in our center. We acknowledge this as a limitation of our diagnostic workup. However, the presence of preserved left ventricular function on formal echocardiography and normal troponin levels collectively support that the pulmonary edema in this patient was not due to cardiac failure. Renal function was also normal, and urine output remained adequate throughout, excluding volume overload secondary to renal failure. The constellation of findings—including eschar, serological confirmation, bilateral pulmonary involvement, and absence of cardiac or renal pathology—strongly supported a diagnosis of scrub typhus–associated noncardiogenic pulmonary edema due to capillary leak syndrome.

Although fluid overload must be considered, we believe it was unlikely in this patient. He received only a single resuscitative saline bolus, after which blood pressure stabilized. There were no signs of systemic overload such as raised JVP, pedal edema, or oliguria, and renal function remained normal. Moreover, a single saline bolus would not be expected to cause clinically significant pulmonary edema requiring oxygen therapy.

ARDS is the most common cause of noncardiogenic pulmonary edema; however, distinguishing it from other forms of noncardiogenic pulmonary edema can be clinically challenging. ARDS is characterized by the acute onset of hypoxemia, bilateral infiltrates on chest imaging, and the absence of left heart failure, often requiring mechanical ventilation. In contrast, although our patient presented with pulmonary congestion on chest radiography and hypoxemia, the clinical course and rapid response to diuretic therapy supported a diagnosis of noncardiogenic pulmonary edema unrelated to ARDS. ARDS typically evolves over days and responds more slowly to treatment. According to the Berlin Definition, ARDS is characterized by acute onset, bilateral opacities on chest imaging, respiratory failure not fully explained by cardiac dysfunction or fluid overload, and impaired oxygenation defined by a PaO₂/FiO₂ ratio ≤ 300 mmHg while the patient is on at least 5 cm H₂O of PEEP or CPAP. In our patient, the PaO₂/FiO₂ ratio was 271.4, but it was measured on room air without any positive pressure support; therefore, the Berlin criteria for ARDS were not fulfilled.

A few cases in the literature have mentioned pulmonary edema in a patient with scrub typhus. Zhou et al. reported the case of a 35-year-old man who initially presented with persistent high fever for seven days, followed by rash, abdominal pain, and peritonitis [10]. Within 24 h of admission, he developed diffuse peritonitis and pulmonary edema requiring mechanical ventilation in the intensive care unit. Unlike our patient, this case was complicated by multiorgan dysfunction, including pulmonary edema progressing to consolidation, elevated troponin levels suggestive of possible myocarditis (although echocardiography was not performed), and peritonitis. Therefore, our report represents a standalone case of scrub typhus–associated noncardiogenic pulmonary edema occurring in the absence of other multiorgan dysfunction.

Interestingly, our patient’s respiratory distress improved rapidly following the administration of low-dose intravenous frusemide. Although capillary leak syndrome–related pulmonary edema is typically noncardiogenic and may not respond well to diuretics, this case highlights that diuretics may provide symptomatic relief in selected, hemodynamically stable patients with evidence of pulmonary congestion. In such situations, the cautious use of low-dose diuretics may help mobilize extravascular lung fluid without compromising intravascular volume status. The prompt clinical improvement in our patient supports this approach, suggesting that even in noncardiogenic pulmonary edema, supportive diuresis may be beneficial in carefully selected cases. A review suggests that in selected, hemodynamically stable patients with noncardiogenic pulmonary edema, cautious use of loop diuretics may provide symptomatic benefit [11]. However, this review is not specific to scrub typhus; it includes all possible causes of capillary leak syndrome.

Timely treatment remains the cornerstone of scrub typhus management. Doxycycline is the first-line treatment for scrub typhus and is considered highly effective [12]. In accordance with UpToDate and local treatment guidelines, severe scrub typhus was managed with doxycycline 200 mg twice daily for the first 48 h, followed by standard dosing [13]. Although our patient had severe disease, oral doxycycline was initiated as intravenous formulation was not available, and given its good oral bioavailability and reliable efficacy, it remains the recommended first-line therapy in our setting. Azithromycin is an alternative, particularly for patients with contraindications to doxycycline, such as pregnant women or young children [14]. Our patient showed a favorable response to doxycycline, with marked clinical improvement within 48 h, which was consistent with expected treatment outcomes.

Conclusion

This case emphasizes the need to maintain a high index of suspicion for scrub typhus in patients presenting with fever and respiratory symptoms, especially in endemic regions. Although pulmonary edema is an uncommon manifestation, it can occur even in the absence of cardiac or renal dysfunction. This case underscores the importance of early recognition and timely initiation of doxycycline even in atypical presentations, to prevent severe complications. Furthermore, low-dose diuretics may provide symptomatic benefits in carefully selected, hemodynamically stable patients with noncardiogenic pulmonary edema not related to ARDS.

Abbreviation

ARDS

Acute respiratory distress syndrome

Author contributions

KS contributed substantially to the clinical management, conception and design of the work, acquisition, analysis, and interpretation of data, and drafting and revision of the manuscript. NP contributed substantially to the clinical management, conception and design of the work, acquisition, analysis, and interpretation of data, and drafting and revision of the manuscript. AS contributed substantially to the clinical management, conception and design of the work, acquisition, analysis, and interpretation of data, and drafting and revision of the manuscript. All authors approved the submitted version of the manuscript and agree to be personally accountable for their own contributions and to ensure the accuracy and integrity of the work.

Funding

This case report did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Data availability

The information used in preparing this case report was obtained from the patient’s bed head ticket at the District General Hospital Kilinochchi, Sri Lanka. This report does not contain any patient data that could compromise privacy. Relevant data can be made available by the corresponding author upon reasonable request, subject to ethical and institutional guidelines.

Declarations

Ethics approval and consent to participate

Not applicable.

Consent for publication

Informed written consent was obtained from the patient’s father for publication of this case report and accompanying images.

Competing interests

The authors declare no competing interests.