Pulmonary Mucormycosis as a Complication
of Chronic Salicylate Poisoning
CARMEN G. ESPINOZA, M.D. AND DEMETRIOS G. HALKIAS, PH.D.
Mucormycosis is an often-fatal opportunistic fungal infection
caused by members of the class Zygomycetes (Phycomycetes),
order Mucorales. Most cases are diagnosed by histologic examination, through the identification of mucormycotic hyphae
in infected tissues. Chronic debilitating conditions accompanied by acidosis such as diabetes mellitus, as well as leukemia,
lymphoma, and immunodeficient states, predispose to the development of this type of opportunistic infection. This report
describes a hitherto undescribed finding, the presence of structures consistent with sporangia in tissue sections, in a case of
pulmonary mucormycosis occurring in a nondiabetic patient
with metabolic acidosis secondary to chronic salicylate poisoning. (Key words: Phycomycosis; Pulmonary mucormycosis;
Fungal infection, lung; Salicylate poisoning) Am J Clin Pathol
1983;80:508-511
THE CLASS ZYGOMYCETES includes the order Mucorales and the order Entomophthorales. Mucormycosis
is a term used to designate infection by members of the
order Mucorales. The order Mucorales includes the genera Mucor, Absidia, and Rhizopus. Species from these
genera are usually found in soil and decaying organic
matter such as fruit, vegetables, and molding bread.
These organisms have been described in hospital environments and as contaminants of commercial elastic
dressings.5,814 Immunocompromised hosts, patients with
certain malignancies, and patients with diabetis-mellitus-associated acidosis are predisposed to the development of mucormycosis. Rarely are healthy people affected by these organisms.2 The diagnosis usually is
made by identification of large, irregular, occasionally
septate hyphae with branching at right angles in sections
stained with hematoxylin and eosin or with silver methenamine. The most frequent forms of the disease are
the rhinocerebral and the pulmonary forms. Cutaneous,
gastric, abdominal-pelvic, cardiac forms occur less
often.9"-12'15
Our report is concerned with a case of pulmonary
mucormycosis in a nondiabetic patient in metabolic
acidosis secondary to salicylate intoxication. In addition,
it also describes the presence of structures consistent
with sporangia in tissue sections.
Received October 27, 1982; received revised manuscript and accepted for publication March 31, 1983.
Address reprint requests to Dr. Espinoza: Laboratory Service, James
A. Haley Veterans Hospital, 13000 N. 30th Street, Tampa, Florida
33612.
Laboratory Service, James A. Haley Veterans Hospital,
and Departments of Pathology and Medical
Microbiology, University of South Florida
College of Medicine, Tampa, Florida
Case Report
A 65-year-old white man was brought to the emergency room of
the James A. Haley Veterans Administration Hospital because of increased shortness of breath and dry cough. The patient's symptoms
had become apparent to the family two days before admission. He
had a long history of alcohol abuse, reportedly drinking one and onehalf cases of beer per day. He had been chronically talcing BC powders
(aspirin 648 mg + salicylamide 194 mg + caffeine 33 mg + potassium
chloride 96 mg) at a rate of 30-40 packets a day. His history includes
partial gastrectomy, cholecystectomy, laminectomy, and chronic obstructive lung disease. On admission he was cooperative and alert but
in moderate respiratory distress. He was thin, unkempt, and afebrile,
with regular pulse of 100 per minute, blood pressure of 106/60 mmHg,
and 24 respirations per minute. Moist rales were present in the left
lower, right lower, and right middle lung fields. Dullness was appreciated in the posterior aspect of the right middle and lower lung fields.
Ecchymoses were present on the toes. No motor or sensory deficits
were detected. Pertinent laboratory data disclosed a salicylate level of
93.4 md/dL (30 mg/dL is the toxic level for this laboratory). The
alcohol level was 0. He had respiratory alkalosis, metabolic acidosis,
hypokalemia, and abnormal coagulation profiles. Blood glucose was
normal on several occasions. Chest x-ray revealed prominent right and
left lower lobe infiltrates consistent with bilateral pneumonia. Sputum
was induced, and cultures showed a mixed flora with no predominant
organisms. On the second day after admission, he became comatose.
CAT scan and lumbar puncture were unremarkable. He required
mechanical ventilation. He developed further ecchymoses on extremities associated with biopsy proven thrombosis of small vessels of skin.
Over the next two weeks, his condition deteriorated with complications
of gangrene of the lower extremities, fever and anuria. Blood cultures
grew Alcaligenes sp. He failed to respond to antibiotics, dialysis, or
supportive therapy. Two weeks after admission he was pronounced
dead.
At autopsy, the lungs were consolidated with thrombosis and infarcts, mainly of the left lung. The lumen and wall of the main pulmonary artery and its branches contained hyphae of mucormycosis
and inflammatory cells (Fig. 1 and 2). In addition to hyphae, sporangiallike structures also were present in some alveolar spaces (Figs. 35). A few budding yeasts and pseudohyphae of Candida species were
identified in only one of the numerous lung sections. No other fungi
or bacteria were identified. Other autopsy findings included severe
atherosclerosis with gangrene of both feet, bilateral renal cortical necrosis, large areas of hepatic centrolobular necrosis, severe acute pancreatitis, and a small well-differentiated adenocarcinoma of the colon
infiltrating down to the serosa.
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Vol. 80 • No. 4
CASE REPORTS
FIG. 1 {upper, left). Section of lung displaying an artery occluded by septic thrombus composed by
mucormycotic hyphae, fibrin and inflammatory cells. Hematoxylin and eosin (X160).
FIG. 2 {upper, right). Broad non-septate hyphae, characteristic of members of the order Mucorales,
infiltrating the lumen (L) and wall (W) of a pulmonary vessel. Gomori Methenamine Silver (X800).
FIG. 3. A {lower, left). Photomicrographs of lung. Numerous sporangial-like structures (B, lower, right) and hyphae
are present infiltrating infarcted lung parenchyma. A. Hematoxylin and eosin (XlOO) B. Hematoxylin and eosin (X400).
509
ESPINOZA AND HALKIAS
510
A.J.C.P. • October 1983
FIG. 4 (left). Close up of one sporangium from Figure 3. Note rhizoids located directly beneath a single sporangiophore
bearing a sporangium. This is characteristic of Rhizopus sp. Hematoxylin and eosin (X 1,000).
FIG. 5 (right). Close up of two structures consistent with sporangia full of sporangiospores. Hematoxylin and eosin (X 1,000).
Discussion
The association of mucormycosis and diabetic ketoacidosis is well recognized and has been the subject
of many reports. It has been postulated that the ketoacidotic state, rather than hyperglycemia, is the most
important triggering factor. Gale and Welch in 19617
first reported the presence of a serum inhibitory factor
in normal serum for in vitro growth of Rhizopus oryzae.
More interestingly, they also found that this inhibitory
activity was absent in the serum of a patient with diabetic ketoacidosis, and following correction of the acidotic state, this inhibitory activity was restored in normal. It appears that the presence or absence of this serum
inhibitory factor correlates well with the extent and severity of clinical disease and may be of prognostic
value." Other conditions frequently accompanied by
acidosis such as uremia10 and diarrhea3 also may be associated with mucormycosis. This case further supports
the important role of acidosis as a predisposing factor
for mucormycosis. This patient's metabolic acidosis was
secondary to chronic salicylate intoxication. This association of mucormycosis and acidosis secondary to salicylate intoxication is not well recognized in the medical
literature. It is mentioned only briefly by Rippon13 without citing a reference. A recent report of a large number
of patients with acid-base disturbances resulting from
salicylates do not mention this complication.6 It is important to be aware of this occurrence because excessive
use of salicylate in adults is becoming more widespread.4
Another interesting aspect in our case was the identification of structures consistent with sporangia in tissue
sections of this patient. The presence of sporangia in
tissue sections has not been reported previously in this
country, although it has been described in the German
literature.' The morphology of the sporangiallike structures situated on stalklike sporangiophores emanating
directly from clusters of rootlike projections (rhizoids)
seen in our patient is characteristic of Rhizopus sp. This
genus was the etiologic agent identified in 13 of 14 culturally proven cases in a recently published study.'' In
summary, we describe a patient with acidosis secondary
to chronic salicylate intoxication complicated with mucormycosis. In addition, sporangiallike structures were
identified in tissue sections of this patient.
Acknowledgment. The authors thank Mrs. Bernadette Farnsworth
for secretarial assistance and Mrs. Pam Reynolds for typing the manuscript.
CASE REPORTS
Vol. 80 • No. 4
References
1. Baker RA: Pulmonary mucormycosis. Am J Pathol 1956; 32:287313
2. Castelli JB, Pallin JL: Lethal rhinocerebral phycomycosis in a
healthy adult: A case report and review of the literature. Otolaryngology 1978; 86:696-703
3. DeWeese DD, Schleuning AS II, Robinson LB: Mucormycosis of
the nose and paranasal sinuses. Laryngoscope 1965; 75:13981407
4. Edwards JL, Taylor RB: Salicylate intoxication in family practice.
Postgrad Med 1980; 67:183-187
5. Everett ED, Pearson S, Rogers W: Rhizopus surgical wound infection associated with elasticized adhesive tape dressings. Arch
Surg 1979; 114:738-739
6. Gabow PA, Anderson RJ, Potts DE, Schrier RW: Acid-base disturbances in the salicylate-intoxicated adult. Arch Intern Med
1978; 138:1481-1484
7. Gale GR, Welch AM: Studies of opportunistic fungi. I. Inhibition
of Rhizopus oryzae by human serum. Am J Med Sci 1961;
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8. Gartenberg G, Bottone EJ, Keusch GT, Weitzmen I: Hospital
acquired mucormycosis (Rhizopus rhizopodiformis) of skin
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Heinemann S: Phycomycosis as postoperative complication of
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Landau JW, Newcomber VD: Acute cerebral phycomycosis (mucormycosis). J Pediatr 1962; 61:363-385
Marchevsky AM, Bottone EJ, Geller SA, Giger DK: The changing
spectrum of disease, etiology and diagnosis of mucormycosis.
Hum Pathol 1980; 11:457-464
Michalak DM, Cooney DR, Rhodes KH, Telander RL, Weinberg
F. Gastrointestinal mucormycosis in infants and children: A
cause of gangrenous intestinal cellulitis and perforation. J Pediatr Surg 1980; 15:320-324
Rippon JW: Medical mycology. The pathogenic fungi and the
pathogenic actinomycetes. Philadelphia, WB Saunders Company, 1974, p 432
Sheldon DL, Johnson WC: Cutaneous mucormycosis. Two documented cases of suspected nosocomial cause. JAMA 1979;
241:1032-1043
Virmani R, Connor DH, McAllister HA: Cardiac Mucormycosis.
A report of five patients and review of 14 previously reported
cases. Am J Clin Pathol 1982; 78:42-47
A Case of Familial Mediterranean Fever with Cutaneous
Vasculitis and Immune Complex Nephritis: Light, Electron,
and Immunofluorescent Study of Renal Biopsy
MENAHEM SCHLESINGER, M.D., JURI KOPOLOVIC, M.D.,
REUVEN J. VISKOPER, M.D., AND NOEMI RON, M.SC.
A 29-year-old patient suffering from familial Mediterranean
fever developed severe myalgia and hematuria. Skin biopsy
showed vasculitis. The kidney biopsy revealed diffuse proliferative and exudative glomerulonephritis. On immunofluorescent examination, IgM deposits accompanied by C 3 were found
in coarse granular peripheral distribution. Electron microscopy
revealed glomerular subepithelial deposits. Familial Mediterranean fever with vasculitis and immune complex nephritis is
discussed (Key words: Familial Mediterranean Fever; Vasculitis; Glomerulonephritis; IgM deposits) Am J Clin Pathol
1983; 80: 511-514
FAMILIAL MEDITERRANEAN FEVER (FMF) is an
inflammatory disease of unknown etiology, characterized by attacks of fever and/or polyserositis involving
mainly the peritoneum, synovium, and pleura. Renal
involvement compatible with immune complex neReceived December 9, 1982; received revised manuscript and accepted for publication April 6, 1983.
Address reprint requests to Dr. Kopolovic: Department of Pathology, The Hebrew University-Hadassah Medical School, P.O.B. 1172,
91120 Jerusalem, Israel.
Barzilai Medical Center, Ashkelon and Department of
Pathology, Hadassah University Hospital and the Hebrew
University-Hadassah Medical School, Jerusalem, Israel
phritis also has been reported,1 but, until now, such complexes have not been demonstrated by immunofluorescence and electron microscopy. This report describes a
patient with FMF who suffered from the combination
of myalgia, deep subcutaneous vasculitis, and immune
complex nephritis demonstrated by light microscopy,
electron microscopy, and immunofluorescence.
Report of a Case
The patient, a 28-year-old man of Jewish Tunisian descent, had a
brother known to suffer from FMF. From the age of 18 years, our
patient experienced recurrent attacks of fever, acute abdominal pain,
and severe arthralgia, necessitating frequent hospitalization. The attacks usually lasted for two to three days. Pleuritis with small pleural
effusions occasionally occurred. Colchicine therapy was commenced
at the age of 24 and continued for three years, following which he
became asymptomatic and therapy was discontinued.
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