Page 16 - JSOM Fall 2019

Delayed Diagnosis in Army Ranger

Postdeployment Primaquine-Induced Methemoglobinemia

Robyn Essendrop, MD *; Nathan Friedline, MD ; John Cruz, DO 3
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ABSTRACT
Presumptive antirelapse therapy (PART) with primaquine for b5R deficiency. Our review of current English-language liter-
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Plasmodium vivax malaria postdeployment is an important ature identified fewer than 10 published cases of symptomatic
component of the US military Force Health Protection plan. PQ-induced methemoglobinemia, which were all described in
While primaquine is well tolerated in the majority of cases, HIV-positive patients treated for Pneumocystis jiroveci pneu-
we present a unique case of an active duty Army Ranger with- monia. Additionally, only two of these cases required treat-
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out glucose-6-phosphatase dehydrogenase or cytochrome b5 ment with methylene blue. We present a unique case of a
reductase (b5R) deficiencies who developed symptomatic met- PQ-induced methemoglobinemia diagnosed in an otherwise
hemoglobinemia while taking PART following a deployment healthy, postdeployment, active duty Army Ranger without
to Afghanistan. G6PD deficiency.

Keywords: presumptive antirelapse therapy; Plasmodium vi- Case Presentation
vax; primaquine; methemoglobinemia
A 22-year-old white Army Ranger presented to our emergency
department (ED) with concern for contrast-induced allergic re-
action following computed tomography pulmonary angiogra-
Introduction
phy (CTPA). On arrival, we noted both labial cyanosis (Figure
Prevention of plasmodial infection remains an important con- 1) and an initial oxygen saturation (Spo ) of 90% without any
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cern among deployed US Servicemembers and encompasses evidence of anaphylaxis or other allergic reaction. Our patient
both primary prophylaxis and PART. Both Plasmodium vi- reported persistent shortness of breath, dry cough, and “blue
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vax and Plasmodium ovale can cause delayed infection due to lips” for the past 2 weeks, which originally began 1 week after
activation of dormant hypnozoites in the liver. The primary returning from a several-month–long deployment to Afghan-
goal of PART is the eradication of intrahepatic P vivax hypno- istan. He reported dyspnea at home after climbing a single
zoites. First licensed in 1952, primaqine (PQ) was the only US flight of stairs and had been unable to resume any of his typ-
Food and Drug Administration (FDA)-approved medication ical work-out routines. He was otherwise healthy and denied
for this purpose until the recent FDA approval of tafenoquine any chest pain, palpitations, leg swelling, hemoptysis, fever,
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in 2018. The Centers for Disease Control and Prevention or history of clotting disorder. Medical workup 6 days earlier
(CDC) recommends that providers consider prescribing PQ was inconclusive with a normal electrocardiogram, chest ra-
to travelers with prolonged exposure to endemic areas where diography, venous blood gas, complete blood count, and ba-
P vivax accounts for >80% of malaria cases. Afghanistan, sic metabolic panel. CTPA at that time was negative for large
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North Korea, and Iran are among the countries with highest
risk of P vivax exposure; the Armed Forces Health Surveil- FIGURE 1 Labial cyanosis pretreatment.
lance Center has identified PART as a key component in the
US military Force Health Protection plan. 4

Prescribing considerations for PQ include ruling out an un-
derlying glucose-6-phosphatase dehydrogenase (G6PD) de-
ficiency, the screening for which is now mandated for all
military personnel. PQ can precipitate both severe hemolysis
and methemoglobinemia in individuals with G6PD deficiency.
Reports of symptomatic methemoglobinemia related to ma-
laria prophylaxis with PQ are particularly rare in the absence
of G6PD deficiency, with the last cases published during the
Vietnam Conflict among a group of soldiers heterozygous for
*Correspondence to ressendrop@gmail.com
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1 CPT Essendrop, LTC Friedline, and CPT Cruz are affiliated with the Madigan Army Medical Center, Tacoma, WA.
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