Case Report M. R. Buhl, T. P. Joseph, B. E. Snelling, L. Buhl

Temporofacial Zygomycosis in a Pregnant Woman Summary: A 38-year-old Omani woman, seven months pregnant, developed extensive zygomycosis involving maxillary and temporal bones. No evidence of any underlying immune deficiency was detected except that which may be attributed to pregnancy. After delivery the patient was treated with repeated courses of amphotericin B, which resulted in a complete clinical resolution. Zygomycosis in uncomplicated pregnancy has not been previously described.

Zusammenfassung: Temporofaziale Zygomykose bei Eine 38j~hrige Frau aus dem Sultanat Oman entwickelte im siebten Schwangerschaftsmonat eine Zygomykose, die die Oberkieferund Schl~ifenknochen befiel. Es bestand kein Anhalt ffir fiber die schwangerschaftsassoziierte Beeintr~ichtigung der Abwehrlage hinaus bestehende Immunst6rungen. Nach der Entbindung wurde die Patientin erfolgreich mit Amphotericin B behandelt und eine komplette klinische Wiederherstellung erreicht. Bisher liegen keine Berichte fiber eine Zygomykose bei unkomplizierter Schwangerschaft vor.

einer Schwangeren.

Introduction Zygomycosis is an uncommon, often fatal opportunistic fungal infection in humans [1]. The causative organism is an aerobic saprophytic fungus belonging to the order of Mucorales of the class Zygomycetes [2]. It is ubiquitous in soil and is present in decaying vegetation. It may also be a laboratory contaminant and is often seen as a bread mold [2]. It can be routinely cultured from the human nose, throat, oral cavity and stool [3]. The fungus has a tendency to invade the vascular system and to occlude arterial blood flow, causing rapid thrombosis, ischaemia and necrosis of the structures supplied by the affected vessels. The invasion frequently involves the tissues of the mouth, the paranasal sinuses, the orbit and brain, depending on the portal of entry [2,4]. We report a case of zygomycosis causing chronic osteomyelitis in both maxillary and temporal bones and in the left zygomatic bone in a pregnant but otherwise healthy woman.

Case Report A 38-year-old Omani woman, seven months pregnant, presented to the dental department in November 1989 with a four-month history of facial swelling, headache and mild droop of the upper eyelid. On examination there was a unilateral swelling of the left side of the face with a left lower motor neuron facial palsy. There were multiple 54 / 230

Figure 1: Computed tomography scan showing destruction of parts of the left zygomatic bone with swelling of surrounding soft tissue.

retained dental roots, all grossly infected with copious purulent discharge. Her complete blood count was normal except for a haemoglobin of 10.5 g/dl (MCV 70.9 fl, MCH 22.4 pg, and serum ferritin 508 ~tg/1) and a sedimentation rate of 40 mm in 1 h. Chest radiograph showed no abnormality. Computed tomography (CT) of the face showed features of chronic osteomyelitis affecting both maxillary and temporal bones and the left zygomatic bone (Figure 1). The infected dental roots were removed. Miconazole treatment was started and continued throughout the pregnancy; although a cure could not be expected, it was hoped that the miconazole might slow the progression of the suspected zygomycosis until the end of the pregnancy, at which time amphotericin B could be given. Further invasive procedures were deferred until after delivery of the patient's child. In March 1990, after delivery, bilateral maxillary sequestrectomy was performed, revealing multiple black necrotic areas with multiple bone sequesters. Microscopic examination of the biopsy specimens showed severe necrotizing osteomyelitis with areas containing large collections of broad, non-segmented hyphae characteristic of zygomycosis

Received: 9 January 1992/Accepted: 28 April 1992 M. R. Buhl, M. D., Ph.D., T. P. Joseph, InfectiousDisease Unit,L. Buhl,

M. D., Dept. of Histopathology,Sultan Qaboos University,P. O. Box 32485, AI Khod, Muscat, Sultanate of Oman; B. E. Shelling, Dept. of Dentistry, A1Nahda Hospital, Muscat, Sultanateof Oman.

Infection20 (1992) No. 4 © MMV MedizinVerlagGmbHMfinchen,Mfinchen1992

M. R. BuM et aL: Temporofacial Zygomycosis

Figure 2: Zygomycetous osteomyelitis in decalcified maxillar bone tissue, characterized by mycelium of 10-25 Ixm in diameter with branched, thin-walled hyphae presenting non-parallel sides and focal bulbous dilatations (PAS stain x 75). Inset: Higher magnification (x 150) of an area showing the mycelium.

(Figure 2). She was treated with intravenous amphotericin B (0.8 mg/kg/day) for six weeks. The treatment was poorly tolerated and repeated transfusions were needed. In April 1991 she received a second course of amphotericin B (1 mg/kg/day) for three weeks, as CT still showed signs of osteomyelitis. This time the treatment was supplemented with intravenous methylprednisolone (25 mg/day) and sodium bicarbonate, which increased the tolerance. A subsequent maxillary biopsy at the end of therapy was negative for the fungus, and a repeat CT scan showed significant improvement. A third course of amphotericin B (1 mg/kg/day) for three weeks was given in May 1991 despite a negative biopsy report. At follow-up three months later, there was no evidence of recurrence. The facial swelling had subsided and the sedimentation rate had returned to almost normal. Discussion

Zygomycosis very rarely, if ever, occurs in patients with an intact immune system. Person-to-person transmission has not been described [1], but nosocomial transmission via air conditioning systems may occur [5], indicating that heavy exposure may contribute to the establishment of clinical infection. The diagnosis of zygomycosis in our patient was made histopathologically by the identification of broad, non-septal, irregularly shaped hyphae invading the tissue and blood vessels, all features of zygomycetes. As is often the case, all cultures were negative, so neither identification of the fungal species [2] nor in vitro sensitivity testing was possible, although the latter is poorly correlated to the clinical effect [6]. According to authoritative sources [2], the term zygomycosis has replaced the older mucormycosis or phycomycosis.

Our patient did not exhibit any signs of the usual predisposing conditions such as diabetes mellitus, acute leukaemia, uraemia, cirrhosis of the liver, severe malnutrition or any other state of immune suppression [1]. She had not previously had any severe infections, and the immunoglobulin levels (Ig A, E, M and G) were all normal, with a normal electrophoresis. By the end of the treatment, the leukocyte count was normal, as was the T lymphocyte count, including absolute numbers of CD4 and CD8 lymphocytes. No laboratory data are available for the period of pregnancy. The patient was found to be HIV negative. A normal type IV reactivity was shown by a positive Mantoux test, without any evidence of active tuberculosis. All of these investigations indicated a normal function of the patient's immune system after treatment and possibly up to the time of pregnancy as well. The microcytic, hypochromic anaemia found in this patient was due to thalassaemia, most likely homozygous ct + thalassaemia. There is no evidence that et thalassaemia minor predisposes to opportunistic infections, as is the case in a thalassaemia major or 13 thalassaemia with transfusion-dependent anemia. Iron overload may predispose to infection, as many microorganisms require iron [7], but in this case the high ferritin level was most likely secondary to the infection. Amphotericin B is still the treatment of choice for zygomycosis, even though newer antimycotics might add to its efficacy [8]. Amphotericin B crosses the placenta readily [9] and should be avoided during pregnancy. In our patient the febrile reaction associated with the administration of amphotericin B was fully controlled by the concurrent use of corticosteroids, which allowed us to gradually increase the dose of amphotericin B to 1 mg/kg/day. Higher doses have no documented therapeutic advantages [6,9]. The patient responded well to antifungal therapy despite a considerable delay in its administration. In addition, an acute invasive course of infection, which is often seen in rhinocerebral zygomycosis [1], did not develop in our patient. Both of these factors indicate that the possible predisposing immune deficiency was only temporary and of a milder degree. The very poor dental status of this patient most likely contributed to the establishment of infection, even though the portal of entry and the source of infection are unknown. Pregnancy tends to aggravate the course of systemic infections such as varicella, influenza, poliomyelitis, listeriosis and tuberculosis, as well as that of superficial candidosis [10]. Specific infections such as falciparum malaria result in not only increased morbidity but also increased mortality during pregnancy [11], which is attributed to immunosuppression during the second half of pregnancy due to increased cortisol levels [11] and placental and lymphocytic depression with low T lymphocyte and CD4 cell counts [10,12].

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M. R. Buhi et al.: Temporofacial Zygomycosis

Women are more susceptible to infections during pregnancy, due to an unknown but presumably complex immunosuppression related to the mechanisms by which the fetal homograft escapes rejection [10]. The temporofacial zygomycosis described in our patient may

have developed predominantly due to impaired immune defences during pregnancy together with a very poor dental status. This condition, which has not been described previously, emphasizes the need for proper dental screening and care during pregnancy.

References

1. Meyer, R. D.: Agents of mucormycosis and related species. In: MandeE. G. L., Douglas, R. G., Bennett, J. E. (eds.): Principles and practice of infectious diseases, 2nd edition. Wiley Medical Publications, New York 1985, pp. 1452-1456. 2. Rippon, J. W.: Zygomycosis. In: Medical mycology,3rd edition. W. B. Saunders, Philadelphia 1988, pp. 681-713. 3. Taylor, C. G., Alexander, R. E., Green, W. H., Kramer, H. S.: Mucormycosis involving the maxilla. Oral Surg. Oral Med. Oral Pathol. 27 (1969) 806-822. 4. Tabachnic, T. T., Levine, B.: Mucormycosis of the craniofacial structures. J. Oral Surg. 33 (1975) 464--469. 5. Weems, J. J., Davis, B. J., Tablan, O. C., Kautman, L., Martone, W. J,: Construction activity: an independent risk factor for invasive aspergillosis and zygomycosis in patients with haematological malignancy. Infect. Control 8 (1987) 71-75. 6. Cohen, J.: Laboratory monitoring of antifungal chemotherapy. Lancet 337 (1991) t577-1580. 7. Bullen, J. J.: The significance of iron in infection. Rev. Infect. Dis. 3 (1981) 1127-1138.

8. Norden, G., Bjork, S., Persson, H., Svalander, C., Li, X. E., Debo, L.: Cure of zygomycosis caused by a lipase-prodncing Rhizopus rhizopodiformis strain in a renal transplant patient. Scand. J. Infect. Dis. 23 (1991) 377-382. 9. Sande, M. A., Mandeli, G. L.: Antifungal agents. In: Gilman, A. G., Goodman, L. S., Ratl, T. W., Murad, F. (eds.): The pharmacological basis of therapeutics, 7th edition. Macmillan Publishing Co., New York 1985, pp. 121%1223. 10. McLean, A. B.: Infection and the antinatal patient. In: MacLean, A. /3. (ed.): Clinical infections in obstetrics and gynaecology. Blackwell Scientific Publications, Oxford 1990, pp. 21-39. 11. Vleugels, M. P. H., Eling, W. M. C., Rolland, R., De Graayy, R.: Cortisol and toss of malaria immunity in human pregnancy. Br. J. Obstet. Gynaecol. 94 (1987) 758-764. 12. Manson-Bahr, P. E. C., Bell, D. R.: Malaria and babesiosis. In." Manson-Bahr, P. E. C., Bell, D. R. (eds.): Manson's tropical diseases. BailtiSre Tindall, London 1987, pp. 25-26.

Book Review T. W a d s t r 6 m , J. Eliasson, J. H o l d e r , A. L j u n g h (eds.)

Pathogenesis of Wound- and Biomaterial-Associated Infections 570 pages, 116 Figures Springer Verlag, London, Berlin, Heidelberg, New York 1990 Price: £ 49.50 Skin and wound infections, especially in immunocompromised and diabetic patients, remain a major threat to the outcome of any clinical treatment. Numbers of implants and materials used in humans increase annually, and so do wound- and biomaterial-associated infections. The book presents the proceedings of a symposium held in Marienlyst, Denmark, in 1989 on the "Pathogenesis of Wound- and BiomaterialAssociated Infections." This interdisciplinary forum for clinicians, specialists in clinical microbiology, immunology, cell biology as well as protein and surface chemists is a major contribution toward improving our understanding of tissue repair mechanisms, pointing out future areas for research efforts and showing models which might be helpful in the pursuit of this research. In summary: - Molecular studies of the host tissue indicate that pathogen interactions might lead to the development of vaccines which produce antibodies already preoperatively. Some staphylococcal carbohydrate surface polymers would be

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candidates for elaborating these antibodies. - Various strategies which microbes use in the "race for the surface" are presented. An understanding of these mechanisms is a prerequisite for the construction of antibacterial biomaterial surfaces. Immunomodulation, possible "medicine of the 90s," might also enhance the normal wound healing process. Several techniques were studied and the results are presented. - I n vitro and animal studies revealed a phase variation of coagulase-negative staphylococci, where gene mechanisms are probably responsible for the regulation of surface properties and virulence factors of the pathogens. - Several animal models are introduced that were used to study wound infections and wound healing. The choice of the right animal model is emphasized, as different animal models might have different results. Although the symposium focussed on gram-positive pathogens only, this publication contributes significantly to our understanding of the pathogenesis of infections and can be recommended to both clinicians and basic scientists. The data presented are still up to date. R. Holzheimer Boston

Infection 20 (1992) No. 4 © MMV Medizin Verlag GmbH Mfinchen, Mfinchen 1992

Temporofacial zygomycosis in a pregnant woman.

A 38-year-old Omani woman, seven months pregnant, developed extensive zygomycosis involving maxillary and temporal bones. No evidence of any underlyin...
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