- Email: [email protected]
Disseminated zygomycosis (mucormycosis) caused by Saksenaea vasiformis
Journal of Infection (1983) 7, 162-165
CASE REPORT Disseminated zygomycosis (mucormycosis)
caused by
Saksenaea vasiformis R. J. Hay, C. K. Campbell, W. M. Marshall*, B. I. Rees* and J. Pincott*
Mycological Reference Laboratory, London School of Hygiene and Tropical Medicine, London WCIE 7HT and *Hospital for Sick Children, Great Ormond Street, London W C I N 3JH Summary A I4-year-old child from Iraq presented with an acute febrile illness accompanied by large necrotic skin lesions and bronchopneumonia from which he subsequently died. The infection was caused by an unusual zygomycete fungus Saksenaea vasiformis. Previous reports of infection with this organism are rare and tissue invasion has usually followed traumatic injury. In the child reported here no predisposing abnormalities were apparent.
Introduction Opportunistic pathogens range from c o m m o n m e m b e r s of the normal microbial flora to unusual environmental saprophytes. Rarely they m a y cause disease in apparently healthy persons although it is then difficult to explain the m e c h a n i s m of pathogenesis. W e are reporting such an event in which a rare and usually opportunistic fungus, Saksenaea vasiformis, caused a fatal infection in a previously healthy child.
Case report T h e patient was a I4-year-old b o y from Baghdad w h o came to L o n d o n for treatment of a severe progressive soft tissue infection of b o t h legs. Five years previously he had had a swollen left knee which had been successfully treated as tuberculosis b y surgical drainage and c h e m o t h e r a p y ; otherwise he was a healthy b u t thin child who regularly attended school. Five weeks before his arrival in L o n d o n a tender swelling had developed in his left thigh; it was incised and treated with several antibiotics. T h e w o u n d failed to heal and other lesions appeared on his right leg. T h e s e rapdily developed central necrosis over the next two weeks. Similar lesions subsequently appeared on his scalp and left cheek adjacent to the nose (Plate I). T h e y progressed in a similar manner b u t more rapidly. H e became febrile and was soon extremely ill. O n admission to the Hospital for Sick Children in L o n d o n there were several soft tissue lesions and signs of severe b r o n c h o p n e u m o n i a which was confirmed b y chest X-ray. Finger clubbing was not present. Tonsillar tissue was visible b u t there was no significant enlargement of l y m p h glands, liver or spleen. His skin was normal apart from the lesions described above. Investigations showed haemoglobin lO.8 g / d l , total white cell count 57 x IO9/1 (87 per 0163-4453/83/o5oi6z + 06 $02.oo/0
© The British Society for the Study of Infection
Saksenaea vasiformis
I63
cent neutrophils, I3 per cent lymphocytes), platelets 250 × io9/1, ESR 24 m m in I hour. Total serum proteins, electrolytes, liver function tests and serum immunoglobulins were normal for his age (IgG I28, IgA 232 , I g M 68 international units/ml). T h e urine contained no sugar, protein, casts or red cells. Sputum was aspirated from the trachea; neither acid-alcohol-fast bacilli (AAFB) nor pus cells were present but Candida albicans and commensal organisms grew in cultures. AAFB were not seen in gastric aspirate. Impression smears as well as a biopsy which included both skin and deeper soft tissues were taken from one of the necrotic skin lesions. T h e child's condition rapidly deteriorated and he required assisted ventilation. Within 24 hours of admission he developed a major arterial occlusion in his left arm. Arterectomy was performed within two hours and an extensive embolus removed from the brachial artery. He died several hours later; permission for autopsy was refused.
Laboratory findings Impressions on glass slides were taken from the vertical cut edge of the biopsy before fixation in order to detect both superficial and deep infecting organisms. Part of the specimen was used for bacterial and viral cultures: the remainder was fixed in neutral buffered formalin, embedded in paraffin wax and sections cut of 5 # m thickness. T h e impressions were stained by haematoxylin and eosin, the periodic acid-Schiff (PAS) technique, and methenamine silver. Sections of the skin showed extensive necrosis and a heavy inflammatory infiltrate throughout the epidermis, dermis and subcutaneous tissue. T h e infiltrate mainly comprised neutrophils but multinucleate giant cells (Plate 2) were also seen. These contained fragments of fungal hyphae which were readily visible by means of the PAS and silver stains. Neither vasculitis nor thrombosis was apparent. T h e stained impressions revealed that the intact hyphae (Plate 3) were large, irregular and ribbon-like, branching, non-septate and nonsporing. T h e appearances were typical of zygomycete hyphae. T h e biopsy material was cultured at 37 °C on both blood and Sabouraud's agar and a slow growth of a white mould was observed. Subculture at 3o °C on Sabouraud's medium resulted in very rapid growth of the mould but sporing structures could not be seen. Attempts to induce sporulation by growth on various mycological media at temperatures from IO °C to 37 °C were unsuccessful. In culture on agar containing Czapek's solution at 26 °C, however, a poor thin hyphal growth supported scanty sporangia typical of Saksenaea vasiformis. These were flask shaped structures with a long neck arising from a short stalk with branched rhizoids (Plate 4). T h e rectangular sporangiospores were formed in venter and neck and were released through a terminal opening. T h e patient's death was ascribed to a disseminated infection caused by the zygomycete S. vasiformis.
Discussion Infection with zygomycete fungi (zygo- or mucormycosis) is well recognised 1 but most infections arise in persons with serious underlying disorders of various types, such as uncontrolled diabetes mellitus, haematological malig-
164
R.j. HAY ET a t .
nancies, severe malnutrition, chronic renal failure or immunodeficiency disorders. Secondary infection of w o u n d s such as burns, where there is extensive necrosis, or in association with contamination o f surgical dressings by the organisms 2 has been reported also. A l t h o u g h our patient was of a thin build his diet was normal and he attended school regularly. T h e r e was no history to suggest an underlying immunodeficiency disorder. H e had had one serious infection of his knee several years earlier b u t had recovered completely from this, apparently w i t h o u t u n d u e delay. His immunoglobins were normal. T h e r e was nothing in the available history to suggest chronic p u l m o n a r y or gastrointestinal disorder or diabetes mellitus. T h e peripheral blood count revealed a massive neutrophil leucocytosis b u t abnormal lymphocytes were not seen. T h e r e was no haematological or clinical evidence of leukaemia or lymphoma. T r a u m a to the skin was not k n o w n to preceed the first lesion. T h e evolution o f the lesions suggested spread via the b l o o d - s t r e a m b u t a site of entry for infection could not be discerned. T h e r e is only one previous report o f an infection with S. vasiformis. ~ T h i s was in a I9-year-old male w h o had a cranial infection following severe trauma to the head. Vigorous surgical and medical treatment (amphotericin B) was curative. In another report 4 o f the same patient, reference is made to two other cases of zygomycosis caused b y Saksenaea. Both followed tissue injury; in one the infection arose in a w o u n d sustained in c o m b a t and in the other the patient had been severely burned. T h e organism Saksenaea vasiformis was first isolated from forest soil in I n d i # and has since been f o u n d in soil in Central America and Israel 4 as well as the U.S.A. 6 At present, it appears to be a rare cause of zygomycosis. It is possible h o w e v e r that there have been m o r e h u m a n cases o f infection with S. vasiformis since in histologically proven cases of zygomycosis the organisms m a y fail to sporulate or even to grow on c o m m o n l y used culture media. Baker 7 suggests that in 5-1o per cent of reported cases o f m u c o r m y c o s i s (zygomycosis) the patients m a y be otherwise apparently normal and in the reported examples of Saksenaea infection (four including our case) all patients had been previously healthy although in three there was underlying severe damage to tissues. T h e clinical features of a rapidly progressive infection with negative cultures accompanied b y large necrotic lesions and signs o f arterial occlusion should alert the clinician to the possibility o f zygomycosis. Biopsy as in this case m a y be the best m e t h o d o f diagnosis. Early treatment is critical as delay is associated with greater mortality, s Extensive surgical d e b r i d e m e n t c o m b i n e d with amphotericin B offers the best choice of success. References
i. Lehrer RI, Howard DH, Sypherd PS, Edwards JE, Segal GP, Winston DJ. Mucormycosls. Ann Intern Med 198o; 93: 93-1o8. 2. Gartenberg G, Bottone EJ, Keusch GT, Weitzman I. Hospital-acquired mucormycosis (Rhizopus rhizopodiformis) of skin and subcutaneous tissue: epidemiology, mycology and treatment. N Engl J Med 1978; 299: I I 15-I 118. 3. Dean DF, Ajello J, Irwin RS, Woelk WK, Skarulis GJ. Cranial zygomycosis caused by Saksenaea vasiformis. J Neurosurg 1977; 46: 97-1o3.
Journal of Infection
Plates I a n d 2
iii~!}i ;iiiiiii
Plate i. T h e patient showing the extent of the left facial lesion.
Plate 2. Giant cells in skin biopsy contain fragments of h y p h a e in their cytoplasm. Periodic acid-Schiff stain x 528.
HAY ET AL.
(Facing p. 164)
Journal of Infection
Plates 3 and 4
g
l
Plate 3. Impressions from the cut surface of the skin biopsy demonstrate a hypha with the characteristic morphology of the zygomycetes. The hypha is branched, ribbon-like and irregular, without septa. Methanamine silver stain x 528.
Plate 4. Flask shaped sporangium typical of S. vasiformis.
HAY
If{"AL.
Saksenaea vasiformis
I65
4. Ajello L, Dean DF, Irwin RS. The zygomycete Saksenaea vasiformis as a pathogen of humans with a critical review of the etiology of zygomycosis. Myeologia I976; 68: 52-62. 5. Saksena SB. A new genus of the Mucorales. Mycologia x953; 45:426-436. 6. Hodges CS. Fungi isolated from southern forest tree nursery soils. Mycologia I962; 54: 22 x-229. 7. Baker RD. Mucormycosis. In: The pathologic anatomy of mycoses. Berlin: Springer-Verlag, I97I : 832-918. 8. Meyer RD, Armstrong D. Mucormycosis--changing status. CRC Crit Rev Clin Lab Sci I973; 4: 421-45I.
CASE REPORT Disseminated zygomycosis (mucormycosis)
caused by
Saksenaea vasiformis R. J. Hay, C. K. Campbell, W. M. Marshall*, B. I. Rees* and J. Pincott*
Mycological Reference Laboratory, London School of Hygiene and Tropical Medicine, London WCIE 7HT and *Hospital for Sick Children, Great Ormond Street, London W C I N 3JH Summary A I4-year-old child from Iraq presented with an acute febrile illness accompanied by large necrotic skin lesions and bronchopneumonia from which he subsequently died. The infection was caused by an unusual zygomycete fungus Saksenaea vasiformis. Previous reports of infection with this organism are rare and tissue invasion has usually followed traumatic injury. In the child reported here no predisposing abnormalities were apparent.
Introduction Opportunistic pathogens range from c o m m o n m e m b e r s of the normal microbial flora to unusual environmental saprophytes. Rarely they m a y cause disease in apparently healthy persons although it is then difficult to explain the m e c h a n i s m of pathogenesis. W e are reporting such an event in which a rare and usually opportunistic fungus, Saksenaea vasiformis, caused a fatal infection in a previously healthy child.
Case report T h e patient was a I4-year-old b o y from Baghdad w h o came to L o n d o n for treatment of a severe progressive soft tissue infection of b o t h legs. Five years previously he had had a swollen left knee which had been successfully treated as tuberculosis b y surgical drainage and c h e m o t h e r a p y ; otherwise he was a healthy b u t thin child who regularly attended school. Five weeks before his arrival in L o n d o n a tender swelling had developed in his left thigh; it was incised and treated with several antibiotics. T h e w o u n d failed to heal and other lesions appeared on his right leg. T h e s e rapdily developed central necrosis over the next two weeks. Similar lesions subsequently appeared on his scalp and left cheek adjacent to the nose (Plate I). T h e y progressed in a similar manner b u t more rapidly. H e became febrile and was soon extremely ill. O n admission to the Hospital for Sick Children in L o n d o n there were several soft tissue lesions and signs of severe b r o n c h o p n e u m o n i a which was confirmed b y chest X-ray. Finger clubbing was not present. Tonsillar tissue was visible b u t there was no significant enlargement of l y m p h glands, liver or spleen. His skin was normal apart from the lesions described above. Investigations showed haemoglobin lO.8 g / d l , total white cell count 57 x IO9/1 (87 per 0163-4453/83/o5oi6z + 06 $02.oo/0
© The British Society for the Study of Infection
Saksenaea vasiformis
I63
cent neutrophils, I3 per cent lymphocytes), platelets 250 × io9/1, ESR 24 m m in I hour. Total serum proteins, electrolytes, liver function tests and serum immunoglobulins were normal for his age (IgG I28, IgA 232 , I g M 68 international units/ml). T h e urine contained no sugar, protein, casts or red cells. Sputum was aspirated from the trachea; neither acid-alcohol-fast bacilli (AAFB) nor pus cells were present but Candida albicans and commensal organisms grew in cultures. AAFB were not seen in gastric aspirate. Impression smears as well as a biopsy which included both skin and deeper soft tissues were taken from one of the necrotic skin lesions. T h e child's condition rapidly deteriorated and he required assisted ventilation. Within 24 hours of admission he developed a major arterial occlusion in his left arm. Arterectomy was performed within two hours and an extensive embolus removed from the brachial artery. He died several hours later; permission for autopsy was refused.
Laboratory findings Impressions on glass slides were taken from the vertical cut edge of the biopsy before fixation in order to detect both superficial and deep infecting organisms. Part of the specimen was used for bacterial and viral cultures: the remainder was fixed in neutral buffered formalin, embedded in paraffin wax and sections cut of 5 # m thickness. T h e impressions were stained by haematoxylin and eosin, the periodic acid-Schiff (PAS) technique, and methenamine silver. Sections of the skin showed extensive necrosis and a heavy inflammatory infiltrate throughout the epidermis, dermis and subcutaneous tissue. T h e infiltrate mainly comprised neutrophils but multinucleate giant cells (Plate 2) were also seen. These contained fragments of fungal hyphae which were readily visible by means of the PAS and silver stains. Neither vasculitis nor thrombosis was apparent. T h e stained impressions revealed that the intact hyphae (Plate 3) were large, irregular and ribbon-like, branching, non-septate and nonsporing. T h e appearances were typical of zygomycete hyphae. T h e biopsy material was cultured at 37 °C on both blood and Sabouraud's agar and a slow growth of a white mould was observed. Subculture at 3o °C on Sabouraud's medium resulted in very rapid growth of the mould but sporing structures could not be seen. Attempts to induce sporulation by growth on various mycological media at temperatures from IO °C to 37 °C were unsuccessful. In culture on agar containing Czapek's solution at 26 °C, however, a poor thin hyphal growth supported scanty sporangia typical of Saksenaea vasiformis. These were flask shaped structures with a long neck arising from a short stalk with branched rhizoids (Plate 4). T h e rectangular sporangiospores were formed in venter and neck and were released through a terminal opening. T h e patient's death was ascribed to a disseminated infection caused by the zygomycete S. vasiformis.
Discussion Infection with zygomycete fungi (zygo- or mucormycosis) is well recognised 1 but most infections arise in persons with serious underlying disorders of various types, such as uncontrolled diabetes mellitus, haematological malig-
164
R.j. HAY ET a t .
nancies, severe malnutrition, chronic renal failure or immunodeficiency disorders. Secondary infection of w o u n d s such as burns, where there is extensive necrosis, or in association with contamination o f surgical dressings by the organisms 2 has been reported also. A l t h o u g h our patient was of a thin build his diet was normal and he attended school regularly. T h e r e was no history to suggest an underlying immunodeficiency disorder. H e had had one serious infection of his knee several years earlier b u t had recovered completely from this, apparently w i t h o u t u n d u e delay. His immunoglobins were normal. T h e r e was nothing in the available history to suggest chronic p u l m o n a r y or gastrointestinal disorder or diabetes mellitus. T h e peripheral blood count revealed a massive neutrophil leucocytosis b u t abnormal lymphocytes were not seen. T h e r e was no haematological or clinical evidence of leukaemia or lymphoma. T r a u m a to the skin was not k n o w n to preceed the first lesion. T h e evolution o f the lesions suggested spread via the b l o o d - s t r e a m b u t a site of entry for infection could not be discerned. T h e r e is only one previous report o f an infection with S. vasiformis. ~ T h i s was in a I9-year-old male w h o had a cranial infection following severe trauma to the head. Vigorous surgical and medical treatment (amphotericin B) was curative. In another report 4 o f the same patient, reference is made to two other cases of zygomycosis caused b y Saksenaea. Both followed tissue injury; in one the infection arose in a w o u n d sustained in c o m b a t and in the other the patient had been severely burned. T h e organism Saksenaea vasiformis was first isolated from forest soil in I n d i # and has since been f o u n d in soil in Central America and Israel 4 as well as the U.S.A. 6 At present, it appears to be a rare cause of zygomycosis. It is possible h o w e v e r that there have been m o r e h u m a n cases o f infection with S. vasiformis since in histologically proven cases of zygomycosis the organisms m a y fail to sporulate or even to grow on c o m m o n l y used culture media. Baker 7 suggests that in 5-1o per cent of reported cases o f m u c o r m y c o s i s (zygomycosis) the patients m a y be otherwise apparently normal and in the reported examples of Saksenaea infection (four including our case) all patients had been previously healthy although in three there was underlying severe damage to tissues. T h e clinical features of a rapidly progressive infection with negative cultures accompanied b y large necrotic lesions and signs o f arterial occlusion should alert the clinician to the possibility o f zygomycosis. Biopsy as in this case m a y be the best m e t h o d o f diagnosis. Early treatment is critical as delay is associated with greater mortality, s Extensive surgical d e b r i d e m e n t c o m b i n e d with amphotericin B offers the best choice of success. References
i. Lehrer RI, Howard DH, Sypherd PS, Edwards JE, Segal GP, Winston DJ. Mucormycosls. Ann Intern Med 198o; 93: 93-1o8. 2. Gartenberg G, Bottone EJ, Keusch GT, Weitzman I. Hospital-acquired mucormycosis (Rhizopus rhizopodiformis) of skin and subcutaneous tissue: epidemiology, mycology and treatment. N Engl J Med 1978; 299: I I 15-I 118. 3. Dean DF, Ajello J, Irwin RS, Woelk WK, Skarulis GJ. Cranial zygomycosis caused by Saksenaea vasiformis. J Neurosurg 1977; 46: 97-1o3.
Journal of Infection
Plates I a n d 2
iii~!}i ;iiiiiii
Plate i. T h e patient showing the extent of the left facial lesion.
Plate 2. Giant cells in skin biopsy contain fragments of h y p h a e in their cytoplasm. Periodic acid-Schiff stain x 528.
HAY ET AL.
(Facing p. 164)
Journal of Infection
Plates 3 and 4
g
l
Plate 3. Impressions from the cut surface of the skin biopsy demonstrate a hypha with the characteristic morphology of the zygomycetes. The hypha is branched, ribbon-like and irregular, without septa. Methanamine silver stain x 528.
Plate 4. Flask shaped sporangium typical of S. vasiformis.
HAY
If{"AL.
Saksenaea vasiformis
I65
4. Ajello L, Dean DF, Irwin RS. The zygomycete Saksenaea vasiformis as a pathogen of humans with a critical review of the etiology of zygomycosis. Myeologia I976; 68: 52-62. 5. Saksena SB. A new genus of the Mucorales. Mycologia x953; 45:426-436. 6. Hodges CS. Fungi isolated from southern forest tree nursery soils. Mycologia I962; 54: 22 x-229. 7. Baker RD. Mucormycosis. In: The pathologic anatomy of mycoses. Berlin: Springer-Verlag, I97I : 832-918. 8. Meyer RD, Armstrong D. Mucormycosis--changing status. CRC Crit Rev Clin Lab Sci I973; 4: 421-45I.