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Diabetes and rapidly advancing pneumonia

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Q1: What are the possible diagnoses and how would you investigate this patient?

The diagnosis is diabetic ketoacidosis in type 1 diabetes mellitus, which was precipitated by fulminant chest infection and omission of insulin. He survived four days without insulin so there was possibly some endogenous insulin production. At presentation, he had metabolic acidosis with high anion gap (pH 7.25, bicarbonate 4 mmol/l, anion gap 37 mmol/l). In addition he had respiratory alkalosis (arterial carbon dioxide tension 1.2 kPa) caused by compensatory mechanisms and lung infection. He recovered from the diabetic ketoacidosis but pulmonary infection worsened leading to ARDS (arterial oxygen pressure/fractional inspiratory oxygen ratio <150 mm Hg). Preterminally, he had a stress induced upper gastrointestinal bleed.

Bacterial infection of the respiratory tract is a common precipitant of diabetic ketoacidosis in diabetes. In addition to the usual organisms (Streptococcus pneumoniae,Haemophilus influenzae),Staphylococcus aureus,Klebsiella species, andPseudomonas species (Pseudomonas pseudomallei) cause pneumonia more often in diabetics.1 Curiously, pneumococcal pneumonia is not common in diabetics.2 Acute tuberculous pneumonia in such a setting is another differential diagnosis. However, diabetic subjects more often have cavitatory disease and a non-segmental distribution.3 Other important organisms, which usually result in fulminant infection in those with diabetic ketoacidosis, are fungi of the family mucoraceae.1Mucormycosis has a special predilection for diabetics especially during diabetic ketoacidosis. Lee et al reviewed 87 cases of pulmonary mucormycosis over the last 30 years, and observed that diabetes mellitus was the most common underlying predisposition (56%) and, of these patients, 20% had diabetic ketoacidosis at presentation.4 Failure to isolate the organism and lack of response to appropriate antibiotics were clues to the suspicion of fungal infection in this patient. Repeated sputum examination for hyphae, pleural fluid culture, bronchoalveolar lavage, and transbronchial lung biopsy should be done for establishing aetiological diagnosis.4

Q2: How would you manage the condition?

Treatment of pulmonary mucormycosis consists of prompt control of blood glucose, ketoacidosis, and administration of amphotericin B in doses of 0.5 to 1 mg/kg/day with a total dose of at least 2.5 to 3 g and aggressive surgical resection.4 5

Discussion

Pulmonary mucormycosis is a life threatening complication of diabetic ketoacidosis. Mucor belongs to the class zygomycetes, a ubiquitous fungus whose commonest route of entry is the respiratory tract.1 Other predisposing conditions for this fungus include neutropenia, lymphoma or leukaemia, and patients on high doses of corticosteroids and desferrioxamine therapy.4

Pulmonary mucormycosis presents as a rapidly progressive pneumonia having symptoms similar to a bacterial infection such as cough, dyspnoea, or pleuritic chest pain and often with haemoptysis. The radiological picture is not specific and includes lobar or multilobar consolidation, solitary or multiple infiltrates, mediastinal widening, bronchopneumonia, cavitation, and fungal ball and occasionally pleural effusion.1 Lesions due to mucorales may expand very rapidly particularly in the immunocompromised host as in this patient.4

The outstanding characteristics of mucormycosis are: (i) ferrophilia and (ii) angio-invasion. During diabetic ketoacidosis, free iron is relatively increased due to impaired binding of iron with transferrin, thereby, favouring growth of mucor.1 Because of its angioinvasive property, it produces tissue infarction and a characteristic blackish inflammatory exudate, thereby producing obstruction in major airways and haemoptysis.1

The only method for diagnosing pulmonary mucormycosis, is histological demonstration of the fungus in lung biopsy material.1Cultures of sputum and biopsy material for mucor frequently are unhelpful with a high false negative rate.1 There are no serological methods for measuring either antibody to the organism or antigen. Frequently, the organism is identified only at necropsy. In this patient postmortem lung biopsy showed right angled branching hyphae consistent with mucormycosis (fig1).

Learning points

  • In a patient with diabetic ketoacidosis and rapidly advancing pneumonia, other than bacterial infection, mucormycosis is an important consideration.

  • Histological demonstration of the fungus either on bronchoalveolar lavage or lung biopsy material is obligatory to diagnosis.

  • Effective treatment of diabetic ketoacidosis combined with amphotericin B and surgical resection of the lesion yields better results.

Figure 1

Microphotograph of the lung tissue showing broad aseptate fungal hyphae (arrows) with early right angled branching in a necrotic tissue background (haematoxylin and eosin × 550).

Treatment of pulmonary mucormycosis rests on good glycaemic control, management of ketoacidosis, and intravenous amphotericin B. Correction of ketoacidosis is vital for successful outcome.6 It has been shown that serum of diabetic patients with ketoacidosis is conducive to the growth of rhizopus in contrast to the normal human serum.7 Amphotericin B is relatively less effective because of: (i) impaired drug delivery to the site of infection due to vascular occlusion and (ii) higher rates of amphotericin B resistance.5 Therefore, aggressive surgical resection of the diseased lobe and amphotericin B therapy is most useful, when the infection is localised. Survival of patients with mucormycosis has improved with this combined approach, as mortality in surgically treated was 11% compared with 68% in those treated medically alone.5

Final diagnosis

Type 1 diabetes mellitus, diabetic ketoacidosis, and pulmonary mucormycosis with acute respiratory distress syndrome.

References

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