Nocardia Sepsis in a Multigravida With Systemic Lupus Erythematosus and Autoimmune Hepatitis

By Cassar, C L

SUMMARY This report describes a pregnant woman with systemic lupus erythematosus and autoimmune hepatitis who presented with threatened labour and acute renal failure. She developed respiratory distress, haematemesis and became coagulopathic. Intrauterine death occurred and she was admitted to the intensive care unit after caesarean section. She suffered sudden cardiovascular collapse and succumbed. At autopsy, Nocardia was cultured from multiple renal abscesses. The co-existence of Nocardia sepsis, systemic lupus erythematosus, autoimmune hepatitis and pregnancy are discussed. This case illustrates diagnostic challenges associated with Nocardia infection in the presence of co-existing disease.

Key Words: Nocardia, pregnancy, systemic lupus erythematosus, autoimmune hepatitis, sepsis

Systemic lupus erythematosus (SLE) nephritis and autoimmune hepatitis (AIH) are uncommon diseases and pregnancy in these patients is associated with higher risks of serious foetal and maternal complications. Treatment with immunosuppressive agents imposes risks of opportunistic infections, such as Nocardia. This article reports an unusual case of a multigravida with systemic lupus erythematosus and AIH who succumbed to Nocardia sepsis.

CASE HISTORY

A 25-year-old woman, 27 weeks pregnant (gravida 4, para 2, miscarriage 1) was transferred to our hospital with threatened labour. Seven years previously she had been diagnosed with SLE and membranous lupus nephritis, WHO class V. She maintained normal serum creatinine with persistent moderate proteinuria. Five years previously, a liver biopsy found severe fibrosis and early micronodular cirrhosis consistent with AIH, grade A2 B2 stage 4. She had been treated for hypertension for one year and denied alcohol or tobacco use.

Her maintenance medical therapy was oral prednisolone 10 mg, azathioprine 50 mg and atenolol 50 mg, but the latter two were ceased during this pregnancy.

On admission, she reported feeling systemically unwell for several weeks with non-specific symptoms: abdominal pain, poor appetite and malaise. She described exertional dyspnoea being present for several months.

On physical examination she had no rash or purpura, but mild peripheral oedema and oliguria. She was afebrile, blood pressure (BP) 130/70 mmHg, pulse rate 95 beats/minute. Oxygen saturation was 97% on room air. She was administered three doses of oral nifedipine 20 mg and two doses of betamethasone 11.4 mgfor neonatal lung maturation. Cardiotocography was acceptable for 27 weeks gestation. The cervix was closed with no liquor evident and contractions ceased. Laboratory investigations (presented in Table 1) demonstrated new onset acute renal impairment and hyponatraemia.

Her clinical condition deteriorated over 36 hours. She began vomiting small volumes of blood and complaining of abdominal pain and noted foetal movements were less pronounced. Urine microscopy and culture was negative. Despite 3000 ml of intravenous crystalloid, a 24-hour urine collection yielded only 314 ml and demonstrated 530 mg/l of protein. A renal physician diagnosed a flare of lupus nephritis as a cause of the acute deterioration and an intravenous methylprednisone infusion was commenced. Continuous slow intravenous crystalloid was recommended for oliguria. Forty hours after admission foetal heartbeat was not detected and ultrasound confirmed intra-uterine foetal death. She was fatigued, dyspnoeic and had recurrent haematemesis.

She had developed new purpura and was bleeding from mucous membranes and intravenous cannulae sites. She had remained afebrile but had evidence of respiratory distress with respiratory rate of 24 breaths per minute and oxygen saturation of 97% on 2 l/min oxygen via nasal prongs. Pulse rate was 104 and BP was 105/65 mmHg. Jugular venous pressure was elevated to 7 cm and bi-basal crepitations were heard on auscultation of her chest. Pathology tests presented in Table 1 demonstrate a worsening coagulopathy and further deterioration in renal function. Obstetricians and intensivists agreed that her clinical deterioration necessitated urgent caesarean section. She was given four units fresh frozen plasma (FFP) preoperatively and taken to the operating theatre for caesarean section under general anaesthesia. A central line showed a central venous pressure (CVP) of 24 mmHg, with a waveform suggestive of tricuspid regurgitation. Upon opening the abdomen, three litres of straw-coloured ascitic fluid was drained and 500 ml of blood was aspirated from a nasogastric tube.

Postoperatively, she was transferred to the intensive care unit (ICU) intubated and ventilated. In view of the unchanged coagulation studies (Table 1) and ongoing bleeding from gastric aspirates and cannulae sites, she was given a further six units of FFP. For six hours she remained stable with a sinus tachycardia of 110 and a blood pressure of 110/60 without inotropic therapy. Chest X-ray showed cardiomegaly and increased interstitial fluid.

Six hours after caesarean section a sudden vaginal haemorrhage occurred. A four unit packed cell and platelet transfusion was commenced in preparation for urgent return to the operating theatre. She rapidly became hypotensive despite resuscitation with large volumes of intravenous fluid, noradrenaline and vasopressin. She quickly deteriorated further to bradycardia, then pulseless electrical activity and cardiopulmonary resuscitation (CPR) was commenced. The laparotomy wound was opened in an attempt to identify bleeding and the aorta was clamped to improve cerebral and coronary perfusion. Despite prolonged CPR and aggressive resuscitation, she succumbed.

Post mortem examination revealed the following: no anatomical abnormalities of the central nervous system, no evidence of infection, haemorrhage or infarction in the brain. The heart showed biventricular hypertrophy and weighed 470 g, with no thrombus and no evidence of endocarditis, infarction or fibrosis. Examination of the lungs revealed pulmonary oedema and congestion, but no infection or consolidation. Small pulmonary vessels were sclerotic and narrowed. There was altered blood in both the oesophagus and stomach, but no varices were demonstrated. The large bowel was normal. The liver showed established micronodular cirrhosis. The kidneys showed bilateral multiple abscesses. A purulent exudate was cultured and grew Nocardia (unspeciated for laboratory technical reasons). The spleen was enlarged with an appearance consistent with septicaemia.

Histology of the placenta revealed frequent areas of infarction and calcification. Large haemorrhage was noted between the villi in the placenta. There was no evidence of chorio-amnionitis.

DISCUSSION

This case is unusual in the co-existence of multiple complex medical conditions in a young pregnant woman. This appears to be the first reported case of fatal nocardiosis in a pregnant woman with SLE nephritis and AIH.

Nocardia is present in soil and decaying organic matter and becomes an opportunistic pathogen in immunocompromised humans. Patients with SLE are susceptible to infections due to intrinsic immunologic deficits and treatment with corticosteroid and immunosuppressive therapy’. Infection is a leading cause of mortality in SLE, accounting for 25 to 37% of deaths. The presence of lupus nephropathy is associated with a lower survival probability2′. Around 2% of infections in lupus patients are attributed to nocardiosis”. Case series and reviews of nocardiosis in SLE find that diagnosis is frequently made post mortem due to difficulty in clinically distinguishing nocardial infection from lupus flair, and the delay in diagnosis due to its slow growing properties in laboratory medium 1,4.

Nocardia enters the body by inhalation or direct inoculation of the skin after trauma. The lung is the most frequent site accounting for about 80% of infections. Haematological dissemination occurs in approximately half of cases and the CNS is the second most common site of involvement, accounting for approximately 15% of cases6. Rare sites in which disseminated infections have been reported include the epidural space7, thyroid8, pericardium9, joint prosthesis10 and sphenoidal sinuses11 but always in combination with pulmonary, CNS or skin infections. Mok et al12 report a rare case of nocardial meningitis in a SLE patient with no evidence of pulmonary or cutaneous involvement. The present case is unique in that the kidneys are an atypical site for nocardial infection and cases of disseminated Nocardia in the absence of pulmonary, CNS or skin involvement are extremely rare.

Leong et al13 discussed several cases where nocardial abscesses in the lung and brain have disappeared without specific treatment, before dissemination elsewhere. This may explain why a primary site of infection was not identified in our patient.

Pregnancy in women with SLE is associated with higher risks of foetal and maternal complications and lupus nephritis further increases this risk5.14.15. However, this appears to be the first case report of a SLE affected pregnant woman diagnosed with nocardial infection. Opsahl and O’Brien’” reported a case of a primigravida with severe pulmonary sarcoidosis on corticosteroid treatment who suffered systemic nocardiosis during her pregnancy. Others have reported cases of Nocardia skin infections’7 and cerebral abscesses18 in healthy pregnant women in whom pregnancy was the only potential reason for immunosuppression. In the present case our patient’s immunological state was impaired by SLE, cirrhosis and corticosteroid use and pregnancy may have further exacerbated this. Furthermore the added physiological demands of pregnancy on multi- system, multiple pathology organ failure is likely to have contributed to her rapid deterioration. Another unusual aspect of the present case is the concomitant pathologies of SLE and AIH. AIH is a rare chronic liver disease of unknown aetiology. Diagnosis is based on histology, biochemistry and immunological markers19. Younger women have more aggressive disease with a high incidence of cirrhosis at presentation20. AIH has extrahepatic manifestations and can coexist with other autoimmune diseases. SLE alone can be associated with raised hepatic transaminases, but cirrhosis is rare. In isolated case reports where AIH and SLE have co-occurred, authors have described difficulty distinguishing primary AIH liver disease with SLE manifestations from liver disease as a manifestation of SLE21,22.

Pregnancy has an unpredictable effect on AIH; some patients experience remission, whilst AIH exacerbations can also occur and are associated with a high rate of maternal and foetal complications20. Adherence to immunosuppressive therapy and close medical monitoring are essential to successful completion of pregnancy in patients with AIH23,24.

In the present case, the patient did not have documented cardiac or respiratory disease although she described exertional dyspnoea for several months. The autopsy findings suggest that significant pulmonary hypertension may have been a co-morbidity. Pulmonary hypertension is a recognised but uncommon complication of SLE and is associated with a very high mortality rate in pregnancy25.

The co-existence of Nocardia sepsis, SLE nephropathy, AIH cirrhosis and pregnancy has not previously been described. Symptoms of Nocardia can mimic lupus flair and usual markers of sepsis were masked or blunted in this patient by concomitant medical conditions. A high index of suspicion should be kept for uncommon opportunistic pathogens in patients with multi-system disease on long-term immunosupression.

ACKNOWLEDGEMENT

Sincere thanks to Dr Michael Corkeron of The Townsville Hospital, for his advice and encouragement and to the family members of this patient who provided consent for this case to be published.

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C. L. CASSAR*

Department of Anaesthesia, The Townsville Hospital, Townsville, Queensland, Australia

* M.B., B.S.(Hons.), B.Sc.(Hons.), Registrar.

Address for reprints: Dr C. L. Cassar, Department of Anaesthesia, The Townsville Hospital, 100 Angus Smith Drive, Douglas, Qld. 4814.

Accepted for puhlication on March 29, 2007.

Copyright Australian Society of Anaesthetists Aug 2007

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