Candidiasis: An unusual cause of persistent high-grade fever in mid-pregnancy

INTRODUCTION

Fever is an unpleasant experience that can cause extreme discomfort at any stage of life. Its occurrence during gestation can increase agony as the parturients invariably have some components of anxiety during pregnancy. Any systemic infection presenting as pyrexia during pregnancy can have adverse effects on the foetal outcome. Although fungal infections are rare in pregnancy, they do occur occasionally. Pyrexia can be a rare presenting symptom of various fungal infections such as blastomycosis and cryptococcosis, but its association with candidiasis is unheard of in the literature.[1] The degree of temperature rise, stage of pregnancy, and duration of the underlying illness are important determinants for the outcome of pregnancy.[2] Fever, resulting from the intrauterine infections, can be extremely hazardous for the newborn.[3] Therefore, timely and appropriate treatment of fever is necessary to decrease the discomfort of the parturient and to prevent any potential foetal morbidity and mortality. We are reporting the successful management of a case of pyrexia of an unknown origin (PUO) who presented to the emergency antenatal clinic and was diagnosed to be a rare case of severe systemic candidiasis with intertrigo.

CASE REPORT

A 29-year-old female in 27th week of her gestation presented to obstetrical emergency ward with chief complaints of high-grade fever for the last 8 days. Initially, she was treated as an outpatient at the community hospital by a primary physician for fever and mild cough. She was prescribed tablet Amoxicillin 500 mg four times daily for 5 days on suspicion of upper respiratory tract infection on an empirical basis. In addition, her routine investigations done at a community hospital revealed a hemoglobin value of 10.8 g%, a random blood sugar value of 132 mg%, a blood count value of 10,600/cumm. No abnormality was detected in the routine urine examination. On the basis of investigation reports, she was discharged home on the same day by the primary care physician after the routine examination. In spite of taking the prescribed medication, no clinical improvement occurred and fever could be controlled only intermittently by administration of antipyretics. However, after completion of the prescribed duration of antibiotic therapy, fever remained persistently high in the range of 100–102 °F. The pregnant state, persistent fever refractory to treatment, discomfort, and resulting anxiety were the main decisive factors, which forced the primary physician to refer the patient to a higher center instead of going for the battery of tests for PUO during the follow-up visit. The entire treatment was carried out at home, and she was never admitted at the community hospital.

On admission at our tertiary care center, besides fever, she did not give any history of bowel symptoms but dysuria was one of the presenting features. After a thorough initial clinical evaluation, all the requisite investigations for possible causes of pyrexia were sent for. Her general physical examination revealed numerous maculopapular lesions over the upper abdomen including the inframammary region. [Figure 1] On local examination of genitalia, a purulent and foul smelling discharge was present at the vagina along with extensive vulval ulceration as well as the presence of papular lesions on the perineum, groin, and inguinal region. The most striking feature during her physical examination were the presence of rashes which the patient did not convey to the primary care physician as these were thought to be of little significance and unrelated to pregnancy by the parturient. Moreover, in an Indian set-up, female pregnant patients are reluctant to allow for complete examination by the attending primary physician. Ultrasonography (USG) examination of the abdomen was not informative of any significant pathology and a live foetus of approximately 27 weeks gestation was confirmed by USG report. Awaiting the laboratory investigations, an urgent physician and dermatologist consultation was sought. She was provisionally diagnosed to be a case of PUO with possibility of systemic bacterial infection and local fungal infection (intertrigo). On the basis of provisional diagnosis, she was prescribed tablet cefoperazone in an empirical manner and local application of clotrimazole powder. The laboratory profile turned out to be absolutely normal including blood count, urine complete and culture sensitivity examination, blood culture and sensitivity, erythrocyte sedimentation rate, malaria parasite film, renal function panel, liver function tests, sputum culture and sensitivity, viral markers for HIV and hepatitis, VDRL, and other pathologies. Other routine investigations such as blood sugar were absolutely normal, but peripheral blood film revealed the presence of normochromic normocytic anemia. In spite of administration of antibiotic therapy, she had persistent fever in the range of 101–102°F with occasional remissions of few hours after administration of antipyretics.

Figure 1

Maculopapular lesions on the upper abdomen and inframammary region

The clinical scenario of refractory fever and the laboratory findings enforced us to review our diagnosis. After thorough discussion among the physician, dermatologist and the obstetrician, a possible diagnosis of intertrigo with severe invasive and systemic candidiasis infection was thought of. The clinical scenario was thought of as a flare-up of opportunistic fungal infection in the context of systemic administration of antibiotics. However, the contradictory fact to this clinical scenario was the presence of these rashes for the last one month. The diagnosis was further confirmed by the presence of candida growth on KOH preparation and she was treated with fluconazole tablet 150 mg once a week, washing with KMnO₄ and local application of clotrimazole powder besides the administration of ongoing antibiotic regimen. She responded to this therapeutic regimen and fever subsided gradually over a period of 2 days. The entire later course of gestation was uneventful, and the patient delivered a normal healthy baby at term pregnancy.

DISCUSSION

Infection with candida species commonly occur during third trimester, but occasionally can occur in the earlier part of the gestation also. However, fever represents one of the serious manifestations of invasive systemic candidiasis and as such has to be treated at the earliest to prevent any potential clinical catastrophes.[45] Before labeling the patient febrile, one must be thoroughly acquainted with the exact definition of pyrexia. In context of various studies, a morning temperature of >37.2 °C (>98.9 °F) or an evening temperature of >37.7 °C (>99.9 °F) establishes a definition of fever.[6] Hyperthermia is defined as a temperature greater than 37.5–38.3 °C (100–101 °F), depending on the reference, that occurs without a change in the body's temperature set-point.[78]

In normal pregnancy, the basal temperature is usually high due to the effect of elevated levels of progesterone. However, the increase in temperature is not greater than 0.5 °C. Pathologically, the cause of pyrexia in pregnancy may be bacterial, viral, protozoan (malaria), or fungal infection. The etiological factors and sources may be genital, urinary, gastro-intestinal, or infection of nervous system and chorioamnionitis. Fever can cause miscarriage, preterm delivery, intrauterine death, neural tube defects, behavioral changes, and central nervous system dysfunction.[3] The literary evidence involving various retrospective studies have revealed that fever during the early pregnancy was a common denominator in women who had children with neural tube defects.[2] The central nervous system begins to form during the third week after conception and neural tube closure occurs between 18 and 28 days. The central nervous system continues to develop throughout pregnancy, making it more susceptible than other organ systems. After the eighth week postconception or after the end of the organogenesis period, organ systems are less susceptible to damage. The association of hyperthermia with myelomeningocele, occipital encephalocele, severe mental deficiency, seizures, hypotonia, micropthalmia, midface hypoplasia limb defects, and abdominal wall defects has been observed in various studies.[3] Fever is reported to be a cause of spontaneous abortion by many researchers.[9]

Typically, there is no major difference in the pattern of investigation for pyrexia in pregnant or nonpregnant females. During treatment of such patients, a thorough history elicitation and complete physical examination is very essential for formulating appropriately planned therapeutic and management strategies. Rarely, an unusual cause can be the cause of hyperthermia, which is difficult to diagnose as it happened in the present scenario.

Intertrigo is an inflammation of the flexural body folds, which occurs most probably due to presence of potential risk factors such as relatively high temperature, moisture, sweating, and friction. Inner areas of thighs and groin, genitalia, under surface of breast, armpits, underside of obese abdominal belly, behind the ears, etc. are the most common sites involved in intertrigo. Bacteria and yeast, which are the normal inhabitants of the skin, multiply in such favorable environment thus causing increased pathological load and resultant damage to the affected areas.

Candida and yeast are normal inhabitants in human beings and is found in smaller amounts in mouth, vagina, digestive tract, and skin. In a healthy person, other bacteria and immune system keep a check on these organisms to acquire a pathological state. Whenever there is a break in these protective mechanisms, candida growth can acquire infectious dimensions. Diabetes, malnutrition, poor hygiene, pregnancy, iron, folate, vitamin B12, and zinc deficiency are the common predisposing factors for growth of candida, which are commonly seen in the developing nations.

Vulvovaginal infections are the most common infections caused by candida albicans.[10] Invasive candida infection is characterized with the presence of fever and shock with systemic rashes leading to skin and mucosal damage. Major vital organs like spleen, liver, lungs, and brain may also be involved in such cases. Systemic candida infection usually occur in people with one or more of the following: skin and mucosal damage, long-term use of corticosteroids, decreased immunity, organ or stem cell transplantation or critical illness requiring hospitalization in intensive care.

Symptoms alone can be diagnostic but for confirmation, microscopic examination of smears, biopsy samples, and candida antibody levels can be measured in blood which helps immensely in establishing the diagnosis.[1112] People with cutaneous lesions are instructed to keep the affected areas dry with personal hygiene and local application of antifungal. In systemic fungal infections oral fluconazole may be effective or intravenous amphotericin-B may be used but the latter is accompanied by the side effects like blurred vision, convulsions, pain, and troubled breathing.[1314] Our case also responded to the oral treatment and the need for administration of intravenous amphotericin-B was avoided.

CONCLUSION

Fever in pregnancy may not only affect the mother, but also the foetal involvement can increase the morbidity and mortality making the outcome of gestation fruitless. Therefore, timely and appropriate treatment should be done. Moreover, we should not ignore even the mild form of fungal infection like candida vaginitis as it also has the potential to spread systemically in the presence of other predisposing factors and eventually patient can develop clinical and obstetrical emergencies.