Pulmonary mucormycosis is an opportunistic pulmonary fungal infection from a fungus belonging to the order Mucorales.
It 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.
Zygomycosis is a superseded term that had under its umbrella multiple species of fungi that were from different orders (e.g. Mucorales and Entomophthorale).
Mucormycosis is not a reportable disease thus rendering the true incidence of infection unknown and may be under-recognized 2. Pulmonary mucormycosis is considered a rare disease most commonly encountered in patients with prolonged neutropaenia, including those with a history of solid organ or hematopoietic stem cell transplantation. Patients in treatment with deferoxamine (iron-chelator) are also at risk 1.
Pulmonary infection is clinically indistinguishable from more common molds such as invasive pulmonary aspergillosis (IPA) 1,2.
Symptoms may comprise fever refractory to broad-spectrum antibiotics, nonproductive cough, and progressive dyspnea. Pleuritic chest pain, hemoptysis, and pleural effusion are seen less frequently. Invasion of the major pulmonary blood vessels by hyphae may lead to massive, potentially fatal hemoptysis. Invasion of adjacent organs by traversing tissue planes, including the diaphragm, chest wall, and pleura have also been described 2.
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 aerosolized 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.
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.
On CT, ground-glass opacities may be encountered 3. Recently the reversed halo sign has been demonstrated as a fairly specific sign capable of suggesting the diagnosis in the correct clinical setting 3-5. In contrast to cryptogenic organizing pneumonia (COP), the peripheral capsule in the reverse 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.
- 1. Bennett JE, Dolin R, Blaser MJ. Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases: Expert Consult Premium Edition - Enhanced Online Features and Print, 8e. Saunders. ISBN:1455748013. Read it at Google Books - Find it at Amazon
- 2. Goldman L, Schafer AI. Goldman's Cecil Medicine: Expert Consult Premium Edition - Enhanced Online Features and Print, Single Volume. Saunders. ISBN:1437716040. (pages 1994-1997) Read it at Google Books - Find it at Amazon
- 3. Georgiadou SP, Sipsas NV, Marom EM et-al. The diagnostic value of halo and reversed halo signs for invasive mold infections in compromised hosts. Clin. Infect. Dis. 2011;52 (9): 1144-55. doi:10.1093/cid/cir122 - Free text at pubmed - Pubmed citation
- 4. Legouge C, Caillot D, Chrétien ML et-al. The reversed halo sign: pathognomonic pattern of pulmonary mucormycosis in leukemic patients with neutropenia?. Clin. Infect. Dis. 2014;58 (5): 672-8. doi:10.1093/cid/cit929 - Pubmed citation
- 5. Choo JY, Park CM, Lee HJ et-al. Sequential morphological changes in follow-up CT of pulmonary mucormycosis. Diagn Interv Radiol. 2013;20 (1): 42-6. doi:10.5152/dir.2013.13183 - Pubmed citation