Abstract
Scrub typhus is a mite-borne rickettsial infection caused by Orientia tsutsugamushi and is transmitted through the bite of larval trombiculid mites. It is an important cause of acute febrile illness in endemic regions. Although the disease typically presents with fever, rash, lymphadenopathy, and eschar, its clinical manifestations are highly variable and may include severe systemic complications. We report a case of scrub typhus presenting with symptomatic hypocalcaemia and hypophosphataemia probably the result of renal tubular electrolyte loss, highlighting a potentially under-recognized metabolic manifestation.
Case report
A 15-year old girl1–3 presented with high-grade intermittent fever with rigors for five days, associated with cough and coryza, and painful intermittent spasms of the left hand for one day. There was no history of seizures, altered sensorium, paresthaesia, trauma, nor drug intake. Her dietary calcium intake was adequate. On admission, she had a temperature of 39.5°C with a tachycardia of 110/min, respiratory rate of 18/min, and blood pressure of 100/78 mm Hg. Examination revealed mild pallor and intermittent spasm of the left hand. Chvostek and Trousseau signs were negative. The liver was tender and palpable 4 cm below the right costal margin with a span of 10 cm. The remainder of the systemic examination was normal. Laboratory evaluation revealed marked hypocalcaemia with serum calcium of 1.37 mmol/L (normal 2.15–2.55 mmol/L), ionised calcium 0.72 mmo/L, and low serum phosphorus of 0.71 mmol/L (normal 0.77–1.45 mmol/L). Serum magnesium was normal (0.86 mmol/L). Serum albumin was 38 g/L and alkaline phosphatase was 91 U/L. Serum parathyroid hormone was 22.9 pg/ml (normal 14.2–75.2 pg/ml), while 25-hydroxy vitamin D was mildly reduced at 46.5 nmol/L. The urine calcium–creatinine ratio was elevated at 0.5 (normal <0.2), indicating increased urinary calcium excretion. Urinary phosphate estimation was not available at our institution. IgM ELISA for scrub typhus was positive. Blood and urine cultures were sterile. Her haemoglobin was 109 g/L, total leucocyte count 10.6 × 109/L, and platelet count 2.846 × 109/L. Serum sodium was 133 mmol/L and C-reactive protein was elevated at 31 mg/L. Renal function tests, serum potassium, coagulation profile, and blood glucose were within normal limits. Serological tests for dengue, leptospirosis, and enteric fever were negative. Electrocardiography done on the second day of admission was normal. Liver function tests were also within normal limits.
Our patient was treated with oral Doxycycline along with intravenous calcium gluconate (10 mL of 10% solution tds), vitamin D supplementation, antipyretics, and supportive therapy. She responded rapidly to treatment. Fever subsided by the third day of hospitalisation and muscle spasms resolved within 48 h. She was discharged on the fourth day on oral calcium and vitamin D supplementation and remained asymptomatic at 2-week follow-up. Repeat investigations after 1 month showed normalisation of serum calcium (2.32 mmol/L), phosphorus (0.87 mmol/L), and parathyroid hormone levels (61.9 pg/mL).
Discussion
Maintenance of serum calcium and phosphate within a narrow physiological range is essential for neuromuscular and cellular metabolic function. Acute hypocalcaemia manifests as neuromuscular irritability and may present with symptoms ranging from paresthesias and muscle twitching to carpopedal spasm, seizures, bronchospasm, laryngospasm, and cardiac arrhythmias. 4 In our patient, severe hypocalcaemia manifested as painful muscle spasms. The elevated urine calcium–creatinine ratio together with hypophosphataemia suggests renal tubular loss of electrolytes. These findings are consistent with scrub typhus–associated tubulo-interstitial injury described in previous studies.5,6 Histopathological studies in affected patients have demonstrated acute tubular necrosis and interstitial nephritis with relatively preserved glomeruli, supporting the possibility of transient renal tubular dysfunction during infection with Orientia tsutsugamushi. 5 Despite significant hypocalcaemia, parathyroid hormone levels in our patient remained within the normal range, representing an inappropriately normal response often described as ‘sick euparathyroid syndrome’. The subsequent rise in parathyroid hormone following clinical recovery suggests transient dysregulation of the calcium–parathyroid hormone axis during acute infection. Similar alterations in parathyroid hormone responsiveness have been reported in other systemic infections, indicating that acute inflammatory states may temporarily disrupt calcium homeostasis. 7 Although mild asymptomatic hypocalcaemia has been described in scrub typhus, more pronounced reductions may have important clinical implications. 8 Severe hypocalcaemia can prolong the QT interval and predispose to cardiac arrhythmias. This becomes particularly relevant when macrolide antibiotics such as Azithromycin are used, as these agents independently prolong the QT interval. 4 In such situations, alternative agents including doxycycline, rifampicin, or tetracycline may represent safer options. 9 Hypophosphataemia due to renal tubular loss may also lead to impaired leucocyte function, platelet dysfunction, haemolysis, encephalopathy, and reduced tissue oxygen delivery due to decreased erythrocyte 2,3-diphosphoglycerate levels.7,10 However, routine phosphate supplementation is generally unnecessary in mild cases because serum phosphate levels usually normalise following treatment of the underlying infection.
In conclusion, scrub typhus may present with symptomatic hypocalcaemia due to renal electrolyte loss. Recognition of this metabolic manifestation and monitoring of electrolytes are important for timely management and may influence antibiotic choice, particularly when QT-prolonging agents such as Azithromycin are considered.
Footnotes
Contributors details
Concept and design of study or acquisition of data or analysis and interpretation of data were responsible of SAZ, PCB, GMV, and SP. Drafting the article or revising it critically for important intellectual content were responsible of SAZ, PCB, GMV, SP, and KP. Final approval of the version to be published was responsible by all the authors approved the version of the manuscript to be published.
Funding
The authors received no financial support for the research, authorship, and/or publication of this article.
Declaration of conflicting interests
The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.