Pulmonary mucormycosis

Pulmonary mucormycosis is an opportunistic pulmonary fungal infection from a fungus belonging to the order Mucorales.

ItPulmonary mucormycosis has to be distinguished from the related counterpart invasive pulmonary aspergillosis (IPA) as modern first-line antifungals typically used for aspergillosis lack activity against fungi causing mucormycosis ¹.

Terminology 

Zygomycosis (pulmonary zygomycosis) is a superseded term that had under its umbrella multiple species of fungi that were from different orders (e.g. Mucorales and Entomophthorale). 

Epidemiology

Mucormycosis is not a reportable disease thus rendering the true incidence of infection unknown and may be under-recognised ². Pulmonary mucormycosis is considered a rare disease most commonly encountered in patients with prolonged neutropenia, including those with a history of solid organ or hematopoietichaematopoietic stem cell transplantation. Patients in treatment with deferoxamine (iron-chelator) are also at risk ¹.

Clinical presentation

Pulmonary infection is clinically indistinguishable from more common moulds such as invasive pulmonary aspergillosis (IPA) ^1,2.

Symptoms may comprise fever refractory to broad-spectrum antibiotics, nonproductive cough, and progressive dyspnoea. Pleuritic chest pain, haemoptysis, and pleural effusion are seen less frequently. Invasion of the major pulmonary blood vessels by hyphae may lead to massive, potentially fatal haemoptysis. Invasion of adjacent organs by traversing tissue planes, including the diaphragm, chest wall, and pleura have also been described ².

Pathology

Microbiology

Agents of mucormycosis are ubiquitous fungi commonly found in decaying organic substrates, including but not limited to bread, fruits, vegetable matter, soil, compost piles and animal excreta. They comprise a group of filamentous fungi in the subphylum Mucormycotina with spores ranging from 3-11 µm in diameter. Thus easily aerosolised and dispersed they can cause infections in humans by either inhalation or when introduced through a cutaneous or percutaneous route. Although frequently harmless for the immunocompetent, they are capable of causing severe, frequently life-threatening infections in humans ^1,2.

Pathogenesis and immunology

The innate immune response to mucormycosis is supplied by mononuclear and polymorphonuclear phagocytes. Only by overcoming these mechanisms can spores germinate into hyphal forms, i.e. the angioinvasive form of infection.While most spores can reach the distal alveolar spaces due to their size, larger spores (>10 µm) may lodge in the nasal turbinates, potentially causing isolated sinusitis ^1,2. Even immunocompetent hosts can develop slowly progressing pulmonary mucormycosis when exposed to inhalation of a high spore inoculum ¹.

Diagnosis

Clinical signs and symptoms of mucormycosis are nonspecific. Microbiological assessment usually makes the diagnosis, but can be hampered by contamination with normal flora. Samples from the nasal cavity are often included (see above). A high level of suspicion in susceptible patient populations is of paramount importance ^1,2.

Radiographic features

Imaging features in pulmonary mucormycosis are nonspecific, it can present as a solitary nodule, lobular consolidation as in pneumonia, cavitary lesion or in disseminated form ².

CT

On CT, ground-glass opacities may be encountered ³. Recently the reversed halo sign orbird's nest signhas been demonstrated as a fairly specific sign capable of suggesting the diagnosis in the correct clinical setting ^3-5. In contrast to cryptogenic organising pneumonia (COP), the peripheral capsule in the reversereversed halo sign tends to be thicker, which is highly suggestive of mucormycosis.

However, differentiation from other infectious agents cannot be made by imaging.

Treatment and prognosis

Surgical treatment in conjunction with systemic antifungal therapy (amphotericin B is the only approved, having many side effects) has been shown to significantly improve survival compared with antifungal therapy alone ¹. Prompt and effective therapy is essential for a successful outcome ^1,2.