Tropical pyomyositis in scrub typhus: a rare association

Abstract

Tropical pyomyositis manifests as single or multiple abscesses inside skeletal muscles and it has a higher prevalence in immunocompromised patients. Scrub typhus, a zoonotic disease is caused by Orientia tsutsugamushi and the clinical manifestations range from simple febrile illness to organ threatening complications. Here, we present a rare case of an immunocompetent young man diagnosed as tropical pyomyositis in association with scrub typhus. Imaging of both thighs revealed multiple intramuscular abscesses. Blood and aspirated pus were culture negative. Patient was treated aggressively with parenteral antibiotics (linezolid, clindamycin and meropenem) and surgical debridement. But, fever did not subside and total leucocyte count remained persistently high. After serological confirmation of scrub typhus, the patient was put on oral doxycycline and he had a dramatic improvement within next few days. To the best of our knowledge, this is probably the first reported case of tropical pyomyositis in association with scrub typhus.

Background

Tropical pyomyositis (TPM) is a bacterial infection causing suppuration within skeletal muscles which clinically manifests as single or multiple abscesses.^{1 2} It is primarily seen in the tropical countries and characteristically associated with immunodeficient conditions such as human immunodeficiency virus (HIV) infection, prolonged use of corticosteroids and malignancies. Most patients with TPM are otherwise healthy without underlying comorbidities, while most patients in temperate regions are immunocompromised or have other serious underlying conditions.³ On the other hand, scrub typhus may have myriads of presentations ranging from simple febrile illness to severe life-threatening complications.⁴ Here, we report a unique case of TPM that was associated with scrub typhus in a young immunocompetent patient.

Case presentation

An 18-year-old previously healthy Indian labourer without any known comorbidity, hailing from a rural area of West Bengal, was admitted in our facility with high grade, intermittent fever and myalgia for the past 2 weeks. It was accompanied with painful swellings over the lateral aspect of left leg, posterior aspect of left forearm, left cheek and anterior aspect of the right thigh. The patient was immunocompetent and did not have a history of hypertension or diabetes. He denied history of trauma in any form. He had no cough, breathlessness, chest pain, burning micturition, rash, eschar, bleeding manifestation or joint pain. There was no history of intravenous drug abuse or high-risk sexual behaviour.

On clinical examination, patient was febrile (oral temperature of 102.1 F), pulse rate 108/min and blood pressure was 104/60 mm Hg. The swellings on the aforementioned areas were firm, tender, fluctuant (maximum size 7×5 cm) (figure 1). Patient was found to have mild pallor and hepatosplenomegaly. A few non-tender, firm and mobile submandibular cervical lymph nodes (maximum size 2×3 cm) were palpable. Other systemic examinations were within normal limits.

Figure 1.

Firm, tender, fluctuant swellings over left cheek (panel A), posterior aspect of left forearm (panel B) and lateral aspect of left leg (panel C).

Investigations

Haematological and biochemical investigations revealed normocytic normochromic anaemia, polychromatic cells, red cell fragments, neutrophilic leucocytosis with toxic granules, high serum lactate dehydrogenase and raised liver enzyme. These features were compatible with possible haemolysis. Serology for HIV1 and 2 antibody was non-reactive. A summary of the results of his laboratory tests is shown in table 1.

Table 1.

Summary of the results of laboratory tests

Tests	Results	Normal range
Haemoglobin	83	120–160 g/L
WBC	22.9×109	4–11×109/L
Neutrophil	77	40%–75%
Lymphocyte	15	20%–40%
Platelet count	180×109	150–450×109/ L
CRP	92	Up to 10 mg/L
Creatinine	71	59–104 umol/L
Albumin	3.0	3.2–5 g/dL
Total bilirubin	0.7	0.1–1 mg/dL
ALT	82	5–35 IU/L
AST	85	5–35 IU/L
ALP	321	110–310 IU/L
Creatine kinase	124	22–198 U/L
LDH	626	230–460 IU/L

ALP, alkaline phosphatase; ALT, alanine transaminase; AST, aspartate transaminase; CRP, C-reactive protein; LDH, lactate dehydrogenase; WBC, white blood cell.

Ultrasonography (USG) of abdomen revealed enlarged liver (17 cm in the midclavicular line) and spleen (13.9 cm) without any ascites. USG of the thigh showed mutliple thick walled hypoechoic collections having irregular walls along with echogenic debris within the thigh muscles (maximum size 7 cm ×5.5 cm). MRI T2-weighted image of both lower limbs revealed hyperintense intramuscular fluid pockets involving rectus femoris and vastus lateralis in axial (panel A, arrow) and coronal section (panel B, arrow) with oedema of the surrounding muscles (figure 2).

Figure 2.

MRI T2-weighted image (T2WI) of both lower limbs showing hyperintense intramuscular fluid pockets involving rectus femoris and vastus lateralis in axial (panel A, arrow) and coronal section (panel B, arrow) with oedema of the surrounding muscles.

Treatment

Patient was initially treated with intravenous injections of linezolid (600 mg two times per day) and clindamycin (600 mg thrice daily) after sending samples of blood and aspirated pus for culture and sensitivity. Gram staining of the aspirated pus was negative for any organism. Subsequently, incision and drainage of larger abscesses were performed. But, fever did not subside and leucocyte count remained persistently elevated (day 2–22.6×10⁹/L, day 4–24.5×10⁹/L). In the meantime, the reports of blood culture and culture of the aspirated pus came as negative. Meropenem (1 gm thrice daily intravenous) was added as a broad spectrum antibiotic on day 4. Regular dressing was performed and the incision and drainage sites were kept clean. But the fever and leucocytosis persisted. Considering the endemicity of tropical infections in India, we searched for malaria, leptospira, dengue and scrub typhus. Though, investigations for malaria, leptospira and dengue were negative; but blood for scrub typhus IgM antibody was positive in high titre (O.D: 2.2188 by ELISA, manufacturer—InBios). Blood or pus sample could not be sent for scrub typhus PCR due to some logistic issues. Oral doxycycline (100 mg two times per day) was immediately started (on day 8) and continued for 10 days. However, his blood was sent for real-time PCR targeting 56 kDa major outer membrane antigen gene of O, tsutsugamushi 6 days after commencement of doxycycline therapy, which came out negative.

Outcome and follow-up

Patient exhibited remarkable clinical improvement, with complete resolution of fever and leucocytosis (day 11–16.6×10⁹/L and day 13–12.3×10⁹/L). The cervical lymph nodes decreased in size and the abscess sites gradually healed over next few days. At 4-week follow-up, he was absolutely well and all abscess sites had healed completely. Repeat scrub typhus IgM antibody assay showed decline in IgM from the initial levels (O.D: 1.164 by ELISA).

Differential diagnosis

In the background of high grade fever, leucocytosis and muscle pain; differentials such as polymyositis, pyomyositis, necrotizing myositis, Leptospirosis, muscle contusion, cellulitis, osteomyelitis, muscle haematoma, muscle rupture/strain or deep vein thrombosis may be considered. However, imaging suggested presence of multiple thick walled hypoechoic collections having irregular walls along with echogenic debris within the thigh muscles and USG guided aspiration revealed collection of pus inside muscle. The most common causative agent of pyomyositis is Staphylococcus aureus. However, blood culture and culture of the aspirated pus were negative in our patient. The persistence of fever and leucocytosis in spite of the use of multiple broad spectrum antibiotics compelled us to perform a thorough search for tropical infections. The positive serology for scrub typhus in our patient (initial positive scrub typhus IgM antibody in high titre with a declining level on follow-up) along with a dramatic response after administration of doxycycline established the diagnosis of TPM associated with scrub typhus.

Discussion

The most common causative agent of TPM is S. aureus accounting for 75% of temperate cases and 90% of tropical cases.⁵ Group A streptococcus accounts for another 1%–5% of cases and other rare causes include Streptococcus (groups B, C and G), Haemophilus, Neisseria, Pneumococcus, Yersinia, Serratia spp, Aeromonas, Escherichia spp, Klebsiella spp, Mycobacterium spp and Pseudomonas spp.⁶ A single group of muscles is usually affected but multiple groups of muscles are involved either simultaneously or sequentially in 12%–40% of cases.¹ The exact pathogenesis of pyomyositis is still unclear. A history of blunt injury or laborious exercise of the involved muscles is present in 20%–50% of cases.⁷ Damaged muscle is prone to hematogenous invasion by bacteria resulting in abscess formation. Abnormality in the immune system is an important factor in many cases. Pus may be sterile in 15%–30% cases and blood cultures usually have low positivity rates.⁸ Serum levels of muscle enzymes are slightly raised or normal in spite of muscle destruction as found in our patient.⁹

Scrub typhus is a zoonotic disease caused by Orientia tsutsugamushi. Though, an eschar formed at the bite site is considered as pathognomonic sign in scrub typhus, it may be absent in 40%–50% of the cases.¹⁰ The various complications seen in scrub typhus are jaundice or transaminitis, acute kidney injury, acute lung injury, septic shock, disseminated intravascular coagulation, myocarditis and meningoencephalitis.¹¹ It is known to affect multiple organs simultaneously due to widespread vasculitis. ELISA detecting O. tsutsugamushi-specific IgM has excellent sensitivity and specificity for the diagnosis of scrub typhus. PCR targeting specific antigen gene of O. tsutsugamushi is preferred for diagnostic confirmation of early disease of less than 1 week duration. Patients often become PCR negative for blood in a few days after starting appropriate antibiotics.¹² The negative PCR in our patient was most probably due to this reason.

To the best of our knowledge, this is the first reported case of TPM occurring in association with scrub typhus. Scrub typhus have been reported to have skeletal muscle involvement in a significant proportion of patients in a study by Kalita J et al.¹³ About 39% of the patients in their study had features of inflammatory myopathy and vasculitis in histopathology. Scrub typhus is rarely associated with any abscess formation. Yi SY et al reported a case of acute pancreatitis with pancreatic abscess in a patient with scrub typhus.¹⁴ They concluded that vasculitis was the most probable aetiology for pancreatitis and pancreatic abscess was a consequence of severe acute pancreatitis.

It is important to be aware of the possible association between scrub typhus and TPM because of the similarity of features like fever, lymphadenopathy, leucocytosis and muscle pain. The diagnosis of scrub typhus had been delayed in our patient because all the manifestations were thought to be related to some pyogenic infection at first. The exact mechanism responsible for development of pyomyositis in association with scrub typhus is unknown. It is likely that those intramuscular abscesses in our patient are a consequence of muscle necrosis due to vasculitis in scrub typhus with subsequent liquefaction and possible secondary pyogenic infection. The dramatic response after administration of doxycycline further hints at the possible correlation between these two entities.

Patient’s perspective.

I was down with fever and severe pain all over my body. I felt extremely ill and weak. I am grateful to the team of doctors for the care and support I and my family received at our hour of greatest need.

Learning points.

• Scrub typhus is caused by Orientia tsutsugamushi and it causes widespread vasculitis along with perivascular inflammation resulting in different end-organ injury.

• Tropical pyomyositis is a great masquerader and it should be suspected in patients having fever, myalgia with or without leucocytosis to avoid delay in diagnosis.

• The exact mechanism responsible for development of pyomyositis in association with scrub typhus is not known. Further studies are needed to explore the association between tropical pyomyositis and scrub typhus.