A presentation of adenovirus with hypokalemia and rhabdomyolysis in pregnancy

Abstract

Background

Adenovirus infection is usually mild in presentation. However during pregnancy, the course can be more severe.

Case

A 21-year-old woman in her second pregnancy presented with abdominal pain, vomiting, and fevers at 34 weeks and 4 days of gestation. Her respiratory pathogen panel on nasopharyngeal secretions was positive for adenovirus. Electrolytes were notable for hypomagnesaemia and persistent hypokalemia (nadir of 2.6 mmol/L) despite repletion but otherwise unremarkable. During her course, she developed rhabdomyolysis. During routine fetal monitoring at 35 weeks and 6 days of gestation, prolonged fetal bradycardia was identified, and an emergency caesarean delivery was performed. The infant had no clinical or laboratory evidence of adenovirus infection. The patient had a protracted clinical course but recovered with supportive care.

Conclusion

Adenovirus can present with severe complications in a pregnant woman including hypokalemia and rhabdomyolysis. The mainstay of treatment is supportive care and monitoring of electrolyte abnormalities and renal function.

Introduction

Human adenovirus, a double-stranded DNA virus, has a wide spectrum of clinical presentations, including gastroenteritis, keratoconjunctivitis, upper respiratory infection, myositis, hepatitis, and myocarditis. ¹ The clinical course is usually mild. However, given the altered immunologic and physiologic state in pregnancy, there can be severe complications in pregnancy. ² Our case demonstrates the clinical course and potential severe complications that can occur in pregnancy including hypokalemia, myositis, and rhabdomyolysis.

Case

A 21-year-old woman at 34 weeks 4 days of gestation presented to another institution with one day history of fevers, abdominal pain, nausea, vomiting, and diarrhea. She was in her second pregnancy. Her child at home had a history of recent upper respiratory viral illness with fever. On initial presentation to the outside hospital, her temperature was 39.4°C, blood pressure was 121/59 mmHg, heart rate was 136 beats per minute, and oxygen saturation was 100% on room air. Her initial examination described as an ill-appearing woman, in no acute distress with a notable tachycardia, but no pulmonary findings, abdomen was soft and non-tender, with hyperactive bowel sounds, and no report of muscle or joint tenderness. Initial complete blood count, renal function, and liver function tests were normal with initial AST 22U/L and ALT 16U/L (Table 1). Her electrolytes were abnormal, with hypokalemia (2.9 mmol/L, normal range 3.5–5.1 mmol/L) and hypomagnesemia (magnesium of 1.2 mg/dL, normal range 1.7–2.4 mg/dL) but no hypocalcemia. Her urine was clear, and urine analysis showed no significant abnormalities.

Table 1.

Significant lab values arranged by hospital day (HD).

	Reference range	Admission	HD2 (Hospital transfer)	HD3	HD4 AM	HD4 PM	HD5	HD6	HD7	HD8	HD9
K	3.5–5.1 mmol/L	2.9	3.6	3.3	2.6	3.6	2.9	3.1	3.4	3.3	3.7
Magnesium	1.7–2.4 mg/dL	1.2	–	–	–	–	–	1.2	1.2	1.6	–
AST	<30 U/L	22	49	63	87	117	100	126	108	71	48
ALT	<30 U/L	16	25	30	35	51	45	54	53	41	34
Creatinine	0.44–1.03 mg/dL	0.59	0.61	0.62	0.59	0.64	0.58	0.61	0.55	0.57	0.59
CK	<200 U/L	–	–	–	–	–	–	3155	2032	1021	–

Note: Absent values were not collected as part of the patient’s clinical care.

Based on her presentation and concern for bacterial infection with unclear source, she was started on intravenous ceftriaxone. Her hypokalemia was corrected with oral potassium chloride supplementation and her hypomagnesemia with intravenous magnesium sulfate. Blood, urine, stool cultures were negative; however, respiratory viral pathogen polymerase chain reaction (PCR) panel was positive for adenovirus and rhinovirus/enterovirus.

On the second day of her admission, she was transferred to our obstetric care center for further evaluation and treatment by the maternal–fetal medicine team. On arrival, her abdominal pain had worsened in intensity and progressed to include bilateral lower back pain. She continued to have fevers up to 39.5°C, and repeat blood and urine cultures showed no growth of bacterial pathogens. Leukocyte count remained normal. She developed mild thrombocytopenia with a platelet count of 140 × 10³/μL and elevation of AST to 49, although ALT and alkaline phosphatase remained within normal range. Her urine remained clear, and a repeat urine analysis remained notable for ketones but was otherwise normal. Due to maternal infection, fetal status was assessed and the fetal heart tracing was reassuring for gestational age.

Her pain worsened into diffuse, intensifying, migratory pain, which the patient initially described as arthralgias. The patient was unable to tolerate lying flat in bed, frequently declined physical examination due to pain, and required increasing dosages of analgesia. On hospital day 3, while her WBC remained stable at 7.6 × 10³/μL, she developed an increased number of immature white blood cells with immature neutrophil percentage of 14 (normal <8%), suggesting a possible infection. Given her fevers, migratory musculoskeletal pain, mild thromobocytopenia, and elevated transaminases, tick-borne illnesses were considered as a potential diagnosis. Anaplasma PCR, Ehrlichia PCR, Babesia PCR, blood smear, and serology for Borrelia burgdorferi and Borrelia miyamotoi were sent and were all negative. With continued high fevers, her antibiotics were changed to ampicillin-sulbactam to include treatment of possible Listeria infection.

Given the adenovirus positive PCR of her nasopharyngeal sample, a serum qualitative adenovirus DNA was sent and returned positive. Since the etiology of her infection was most consistent with a viral infection with positive viral serology, antibiotics were discontinued on hospital day 5. Secondary to her continued severe musculoskeletal pains, she refused fetal monitoring at times during her hospital admission. She continued to have persistent hypokalemia with a nadir of 2.6 mmol/L, which responded with oral potassium repletion. She also had continued hypomagnesemia treated with oral magnesium oxide. Total WBC count remained in the normal range throughout her illness.

The migratory musculoskeletal pain persisted and her transaminases continued to rise with AST greater than ALT, with a peak of 117 U/L and 51 U/L, respectively, on hospital day 6. Due to these transaminase abnormalities and severe pain, there was concern for rhabdomyolysis. Creatinine kinase (CK) was 3155 IU/L, suggesting a diagnosis of rhabdomyolysis. Supportive management was continued with intravenous fluids, antipyretics, and pain medication. Her renal function remained normal throughout her hospital course. Her phosphorus and calcium levels were normal throughout her illness.

On hospital day 8, her fevers subsided, her musculoskeletal pain was improving. Fetal monitoring was initially reassuring, but then had several recurrent late decelerations that did not resolve despite resuscitative efforts, including maternal repositioning and intravenous fluid administration. The fetal heart tracing demonstrated a prolonged deceleration with a rate of less than l10 bpm for greater than 10 min, and the decision was made to proceed with emergency delivery via caesarean section. An uncomplicated low-transverse caesarean delivery was performed at 35 weeks and 6 days of gestation. APGAR scores were 8 and 8 at 1 and 5 min. The infant was admitted to the neonatal intensive care unit. The infant initially required oxygen via continuous positive airway pressure, but was weaned to room air on day of life 2. The infant had a respiratory pathogen PCR panel and adenovirus PCR performed because of concern for respiratory droplet transmission. Both of these were negative and the infant did not show any signs of adenovirus infection.

Over the next several days following her caesarean delivery, the patient’s migratory pain improved. She remained afebrile. On hospital day 12, she was discharged home.

Discussion

Described here is a severe case of adenovirus in a pregnant woman complicated by hypokalemia and rhabdomyolysis. There are several reported cases of rhabdomyolysis attributable to adenovirus^3–5; however, no reported cases in a pregnant woman. Normally, rhabdomyolysis can cause hyperkalemia due to muscle cell electrolyte release; however, this case had hypokalemia that required repeated replacement (Table 1). Hypokalemia can contribute to development of rhabdomyolysis through deficient microvascular functioning leading to local muscle ischemia and necrosis. ⁶

Hypokalemia in pregnancy itself has been linked to pregnancy-induced rhabdomyolysis. While a slight drop in average potassium has been reported comparing non-pregnant and pregnant women (4.25 mmol/L in non-pregnant and 4.01 mmol/L in pregnancy), this change in physiology does not explain the nadir of 2.6 mmol/L in this case. ⁷ Several causes of hypokalemic rhabdomyolysis in pregnancy have been reported, including renal tubular acidosis, hyperemesis gravidarum, and excessive baking soda ingestion.^8–10 Of note, these latter cases had lower potassium values than in this case: 1.8 mmol/L for hyperemesis gravidarum and 1.7 mmol/L for baking soda ingestion versus a nadir of 2.6 mmol/L in this case.

In our patient, it is possible that she became hypokalemic due to the gastrointestinal symptoms of her adenoviral infection, including vomiting and diarrhea. Whilst the hypomagnesemia is likely to have strongly contributed to her persistent hypokalemia, other causes of hypokalemia were felt to be less likely. This included hyperaldosteronism (unlikely as this patient was normotensive), renal tubular acidosis (this patient had no evidence of metabolic acidosis as seen by a normal bicarbonate), and interstitial nephritis (as she demonstrated a normal creatinine and urinalysis without WBC or WBC cases). In this situation, her hypokalemia may have either caused her rhabdomyolysis or predisposed her to the development of rhabdomyolysis from her adenovirus infection. Treatment of adenoviral infection remains supportive and includes anti-pyretics, pain control with medications, intravenous fluids, and electrolyte repletion. There are currently no anti-viral medications approved during pregnancy for this viral infection. When complicated by rhabdomyolysis, monitoring electrolyte abnormalities and renal function is essential. With this case, severe myalgias peaked on the fourth day of illness and then slowly improved over the next week.

While the patient in this case did also test positive for rhinovirus/enterovirus, which are unable to be distinguished in this particular lab’s respiratory pathogen panel, the clinical presentation of febrile illness, abdominal pain, and diarrhea was atypical for rhinovirus, although it could be consistent with enterovirus. Both of these viral infections can be persistently positive on respiratory pathogen PCR panels. Since this patient had positive adenoviral DNA in the blood and a consistent clinical illness, we felt that adenovirus virus infection was the most likely culprit and the rhinovirus/enterovirus positive result was more likely the result of prolonged shedding from a prior infection versus asymptomatic infection, although they could have contributed to her clinical picture as well.

In our case, there was no vertical transmission of adenovirus to the patient’s infant after delivery. This virus has not been shown to cause trans-placental infection. However, there have been previous reported cases of severe neonatal adenovirus infection attributed to fecal-oral and respiratory transmission. ¹¹ Infection control measures were instituted including strict hand washing and respiratory precautions for those visiting the patient and infant in order to mitigate the risk of transmission.