Phialophora richardsiae Infection in Humans
David L. Pitrak, Elmer W. Koneman, Robert C. Estupinan, and Johnny Jackson
From the Section of Infectious Diseases, Department of Medicine, and the Section of Microbiology, Division of Clinical Pathology, Department of Pathology, University of Illinois College of Medicine, Chicago, Illinois
Phialophora richardsiae infection in humans is rare. The first human isolate was recov- ered from a patient with a phaeomycotic cyst in 1968. Since 1975 seven other cases have appeared in the world literature, and an additional case is reported here. The mean age of these nine patients was 61.4 years. Two patients had diabetes mellitus, one had diabetes mellitus and disseminated adrenocortical carcinoma, and one had a myeloproliferative disorder. The mode of acquisition was presumed to be inoculation with contaminated plant material, but a history consistent with an inoculation injury was obtained in only four patients and a retained splinter was found in the lesion of only one patient. Infection with P. richardsiae was not associated with systemic symptoms or signs. Six patients presented with a single subcutaneous cystic granulomatous lesion. One patient had chronic dacryocystitis. More extensive or invasive disease occurred in two patients, both with an ultimately fatal underlying neoplastic process. A specific etiologic diagnosis was made by culture of purulent material obtained by excisional biopsy in six patients, incision and drainage in one patient, aspiration in one, and spontaneous drainage in one. Subcutane- ous nodules were cured with surgical excision. There is insufficient information concern- ing antifungal therapy to recommend its use.
Phialophora richardsiae is one of the many demati- aceous (darkly pigmented or black) fungi that can be isolated from plant material and soil. It is a com- mon contaminant of wood and is an industrial nui- sance, causing blueing of wood pulp and paper. P. richardsiae and other members of the genus Phialophora, as well as other related fungi, can cause disease in humans, most often manifested as an in- fectious subcutaneous granuloma or abscess [1-4]. Subcutaneous phaeohyphomycosis, phaeosporotri- chosis, hyphodermomycosis, subcutaneous mycotic cyst, and phaeomycotic cyst are all names that have been used to refer to this form of dematiaceous fun- gal infection.
Schwartz and Emmons obtained the first human isolate of P. richardsiae from a subcutaneous abscess in 1968 [5]. Since that time seven other cases of hu- man infection with P. richardsiae have been reported, all in the past 13 years [6-11]. We report a case of phaeomycotic cyst due to P. richardsiae and review the previously reported human infections caused by this organism.
Received for publication 18 September 1987 and in revised form 18 April 1988.
Please address requests for reprints to Dr. David Pitrak, Sec- tion of Infectious Diseases, Department of Medicine, University of Illinois College of Medicine, 840 South Wood Street, Chicago, Illinois 60612.
Case Report
A 60-year-old woman with hypertension, diabetes mellitus, and atherosclerotic heart disease sought medical attention for a lump on the medial aspect of her left foot. The lump had been present for ~6 weeks, causing mild discomfort but not interfering with ambulation. She denied any recent trauma or breaks in the skin, but she recalled lacerating her foot at that exact location at age 9 years. She recently noted 2+ urine tests for glucose but denied other specific symptoms.
Physical examination revealed an obese but other- wise well-appearing woman. She was afebrile, and her vital signs were normal. A hyperpigmented area was seen on the medial aspect of the left foot (fig- ure 1). Palpation of the area revealed a subcutane- ous cystic nodule 1.0 cm in diameter. The overlying skin was intact. A 1.2-cm linear scar was clearly visible just next to the cyst. There was no regional lymph- adenopathy. Examination failed to reveal any evi- dence of peripheral neuropathy or vascular insuffi- ciency. Aspiration of the cyst was performed, and the material was sent for culture. After 48 hours’ in- cubation at 35°C-37℃, a mold grew on the blood agar plate. The identification of P. richardsiae was made; subsequently the entire subcutaneous nodule was excised. The patient recovered uneventfully and 14 months later was still free of the infection.
Colonial morphology. On potato dextrose agar the subculture of the original clinical isolate formed a rough, velvety-to-low-wooly, gray-brown colony with an entire margin measuring 2.5 cm after 10 days of incubation at 30℃ (figure 2). The reverse side was a dark brown-black. Subculture to 2% Sabouraud dextrose agar yielded a colony 6 cm in diameter in 10 days at 30℃, which had a distinct faint-red tinge. The reverse side of the colony was burgundy red, with
the pigment confined to the mycelial mat and with no leaching into the agar.
Microscopic features. The microscopic appear- ance varied depending upon the area from which the mounts were made. In the less-mature, actively grow- ing portion of the colony, the hyphae were uniform in size but relatively narrow, averaging 2-3 um in di- ameter. They appeared hyaline, and septations were not conspicuous. A few bottle-shaped phialides with tapered tips 8-12 um in length were derived irregu- larly from the hyphae. Elliptical yellow-brown phialo- conidia 1-2 um in length lined up in single file along the sides of the phialides and along the hyphae (fig- ure 3).
Mounts from the older areas of the culture showed uniform yellow-brown hyphae with prominent sep- tations. The phialides tended to be longer than those in less-mature areas, measuring up to 25 um in length. Sporulation was heavy, with a tendency for the phialoconidia to form clusters at the tips of the tapered phialides (figure 4). These phialoconidia were more spherical, slightly larger, and more deeply stain- ing than the less-mature ones. Many of the mature phialides showed apical flaring and saucer-like col-
larettes (figure 5), distinctive microscopic features by which P. richardsiae can be differentiated from other Phialophora species.
Histologic features of tissue biopsy. A 1.5-cm piece of skin and a 0.8-cm nonencapsulated, nodu- lar mass in the deep dermis extending into the sub- cutaneous fat were submitted for histologic study. Microscopic examination of the hematoxylin-eosin- stained tissue sections revealed an intact hyperkera- totic epidermis. The nodular area of induration in the deep dermis revealed a small central area of necrosis containing a scant amount of cellular de- bris. A concentric zone of dense fibrosis with hyalini- zation surrounded this core, and it in turn was sur- rounded by a zone of inflammatory reaction composed of large macrophages, lymphocytes, oc- casional giant cells, and a few plasma cells (figure 6). Acid-fast stains were negative. Sections stained with Gomori methenamine silver (GMS) revealed a few sparse hyphal fragments adjacent to the central area of necrosis (figure 7). Similar fragments were
seen in sections stained with periodic acid-Schiff (PAS). Grains, granules, or sclerotic bodies charac- teristic of chromoblastomycosis and mycetoma were not observed in these sections.
Antifungal susceptibility tests. Antifungal sus-
ceptibility tests with amphotericin B and 5-fluoro- cystosine (5-FC) were performed on a pure subcul- ture of the original isolate at the Mayo Medical Laboratories, Rochester, Minnesota. The methods described by Shadomy were used [12]. The MICs for amphotericin B and 5-FC were 0.6 µg/mL (reported as sensitive) and 160 µg/mL (reported as resistant), respectively.
Case Reviews
Table 1 summarizes the clinical characteristics of the nine reported cases of human infection due to P. richardsiae. The patients ranged in age from 43 years to 80 years, with a mean age of 61.4 years. Six patients were male, and three were female. Four pa- tients were from the United States, including one from Puerto Rico; one was from Jamaica; and one was from Germany. Nationality was not specified for three. Only patients 2 and 5 acquired their dis- ease outside the United States. Patient 4 had resided in the United States for several years, had visited Puerto Rico only once since coming to the United States, and developed his lesion in the United States.
The lesions were located on the upper extremities in four patients; a single digit was involved in three and the olecranon bursa in one. Four patients had lower extremity lesions, with the foot involved in three and the lower leg in one. A discrete nodule could be palpated in six patients. One patient had
an ulcerative lesion with multiple abscesses and draining sinus tracts over the lower one-third of his right leg. Another patient had drainage from an ul- cerative lesion on the dorsum of the right foot. The duration of disease was reported in eight cases and ranged from 1 month to 30 years. Patient 2 had the unique presentation of chronic dacryocystitis with a 2- to 3-mm “stone” in the lacrimal sac.
Systemic signs or symptoms were lacking or were not reported for six patients. One patient presented with ascites and dependent edema complicating adrenocortical carcinoma with intraabdominal dis- semination and hepatic metastases. Another patient presented with nonketotic hyperosmolar coma due to diabetes mellitus. Patient 7 presented with fever and a right upper lobe pulmonary infiltrate, in ad- dition to the draining lesion in her right foot. She had been evaluated previously for recurrent fevers and hepatosplenomegaly associated with a my- eloproliferative disorder. She eventually died of dis- seminated nocardiosis, and it is doubtful that her fever was due to infection with P. richardsiae. In ad- dition to the patients with adrenocortical carcinoma and myeloproliferative disorder, three other patients had a chronic underlying medical illness. One pa- tient had hypertension and another mild congestive heart failure. Three patients had diabetes mellitus (including the patient with adrenocortical carci- noma, who was also diabetic for 3 months).
A history of trauma or inoculation injury could not be elicited or was not reported in five patients. Another patient denied trauma but remembered working with plywood 1 month before a nodule ap- peared on his left index finger. A splinter was found in the lesion at the time of surgery, and it is likely that subcutaneous inoculation occurred while the pa- tient was working with plywood. The patient with the olecranon mass had suffered a puncture wound to the elbow from a thorn. In one patient a subcuta- neous nodule arose 3 months after a steroid injec- tion for extensor tendonitis. Our patient recalled lacerating her foot at the exact site of her subcuta- neous nodule 51 years before the appearance of the lesion.
Complete excision of a discrete nodule was per- formed in five patients. Cure was achieved in all cases, although the duration of follow-up was speci- fied in only two cases. One patient was cured after incision and drainage of a discrete nodule and was still free of disease 2 months later. The patient with dacryocystitis had a “stone” removed from the lac-
| Patient | Age (y)/ sex | Country of origin | Location of infection | Previous trauma | Duration of illness | Underlying disease | Systemic symptoms and signs | Culture source | Histology | Treatment | Outcome (follow-up period) |
|---|---|---|---|---|---|---|---|---|---|---|---|
| no. [refer- ence] | |||||||||||
| 1 [5] 2 [6] | 80/M 50/F | United States Germany | 1.5-cm tender nod- ules on left fifth finger Dacryocystitis with a 2-3-mm "stone" in lac- rimal sac of right eye | None Unknown | Several months 12 y | Mild heart failure Unknown | None Unknown | Excisional biopsy. "Stone" from lac- rimal sac | Fibrous capsule, granulomatous inflammation, central necrosis, hyphae Epithelial cells and leukocytes sur- rounded by hyphae | Excision Unknown | Cured Unknown |
| 3 [7] | 79/M | United States | 2-cm x 5-cm nod- ule over olecra- non process of left elbow | Puncture wound from thorn | 30 y | None | None | Excisional biopsy | Fibrous capsule, granulomatous inflammation, central necrosis, hyphae | Excision | Cured (4 mo) |
| 4 [8] | 65/M | (U.S.) Puerto Rico | Painful swelling on sole of right foot | None | Unknown | Diabetes mellitus | None | Incision and drainage | Not done | Incision and drainage | Cured (2 mo) |
| 5 [8] | 43/M | Jamaica | Ulcerative lesions with draining sinus tracts over lower 1/3 of leg | None | 1 mo | Diabetes mellitus, disseminated adrenocortical carcinoma | Ascites, pedal edema, diabetic ketoacidosis | Spontaneous drainage | Multiple micro- abscesses in dermis, hyphae | None | Died |
| 6 [9] 7 [10] | 52/M 70/M | United States United States | 1-cm mass on volar aspect of left index finger Draining sinus dorsum of right foot | Working with plywood 6 mo previously None | 5 mo >2 y | None Myeloprolifera- tive disorder | None Fever, pulmonary infiltrate | Excisional biopsy Bone biopsy | Granulomatous inflammation. acellular debris, hyphae, retained splinter Granulomatous inflammation, necrotic bone, hyphae | Excision Surgical debride- ment, ampho- tericin B and 5-FC | Cured Died |
| 8 [11] | 54/M | United States | 0.7-cm mass over dorsum middle phalanx of right index finger | Steroid injection | 3 mo | None | None | Excisional biopsy | Fibrous capsule, granulomatous inflammation, acellular debris, hyphae | Excision | Cured |
| 9 [PR]* | 60/F | United States | 1.0-cm pigmented nodule on medi- al aspect of left foot | Laceration of foot at age 9 y | 1.5 mo | Diabetes mellitus, hypertension | None | Aspiration | Fibrous capsule, granulomatous inflammation, central necrosis, hyphae | Excision | Cured (14 mo) |
* PR = present report.
rimal gland, but the extent of the procedure per- formed and the final outcome were not stated in the report.
Patient 7 did not have a discrete lesion and received antifungal therapy with amphotericin B (1 week, to- tal dose of 161 mg), followed by 5-FC (2.5 weeks, 150 mg/[kg·d]). Debridement of the infected bone of the right foot was also performed. Despite in vitro susceptibility of the fungus to amphotericin B, drain- age of the purulent material persisted after 1 week of amphotericin B therapy and the 2.5-week course of 5-FC. However, 3 weeks after cessation of antifun- gal therapy, the lesion resolved spontaneously. It is unclear whether antifungal therapy contributed to the outcome. The patient was admitted 2 weeks later and subsequently died of a rapidly fatal disseminated nocardial infection.
Patient 5 also had more extensive disease, with draining sinus tracts over the lower one-third of his right leg. He died 6 weeks after presentation, with no reference by the authors as to whether the pa- tient received antifungal therapy or underwent sur- gical debridement. At postmortem examination mul- tiple microabscesses in the dermis with extension into the epidermis were noted. Much of the epidermis was destroyed. However, except for focal fat necrosis, the subcutaneous tissue was not involved. The patient’s death was attributed to metastatic adrenocortical carcinoma and not to disseminated fungal disease.
In seven cases P. richardsiae was isolated from purulent material. Specimens were obtained by aspi- ration in one patient, by incision and drainage in one patient, from culture of spontaneous drainage in one patient, and from excision of a subcutaneous lesion in four patients. In the case of patient 2, the fungus was isolated from culture of the “stone” removed from the lacrimal sac. In patient 7 the organism grew from bone obtained by surgical debridement but did not grow from purulent material draining from the open lesion (although it was not specified whether this material was sent for fungal culture).
Histologic examination of tissue was done in seven patients. The characteristic finding in six patients was a granulomatous inflammatory reaction, often with giant-cell formation. Each of the five discrete nodular lesions had a dense fibrous capsule, and an area of central necrosis was present in four of these lesions. The bone from patient 7 showed necrosis with surrounding granulomatous inflammation. Only the tissue from patient 5 had the histologic ap- pearance of multiple microabscesses composed of
aggregates of granulocytes, as well as lymphocytes. Hyphal elements could be demonstrated in the tis- sue sections from all pathologic specimens with GMS and PAS stains. Hyphal elements were also seen on microscopic examination of the “stone” removed from the lacrimal sac of patient 2, which contained epithelial cells and leukocytes as well.
The information regarding susceptibility testing of P. richardsiae or other dematiaceous fungi is limited. Corrado et al. looked at the susceptibilities of the isolates from their two patients to amphoteri- cin B, 5-FC, and miconazole [8]. They performed susceptibility tests on cultures after 6 days and 3 weeks of incubation. The 6-day cultures showed a predominance of primary phialoconidia, whereas secondary phialoconidia predominated at 3 weeks. The isolates were resistant to 5-FC at both 6 days and 3 weeks of incubation. The 6-day cultures were also resistant to amphotericin B and miconazole; with the 3-week cultures the MICs were 7.8 µg/mL for amphotericin B and 62.5 µg/mL for miconazole. When the inoculum was decreased from 105 spores/mL to 103 spores/mL, both isolates appeared more susceptible to all three agents, at both 6 days and 3 weeks of culture. However, this apparent in- crease in susceptibility could be offset by incubation for 72 hours instead of 48 hours. The isolate from patient 7 was tested for susceptibility to amphoteri- cin B, miconazole, clotrimazole, and ketoconazole. The inoculum was not adjusted for a standard spore count, and testing was performed only after 48 hours of growth. Of all the agents tested, amphotericin B appeared to be the most active, with MICs and MBCs of 0.15 µg/mL and 0.31 µg/mL, respectively. Micon- azole and ketoconazole had MICs of 0.24 µg/mL and 0.5 ug/mL, but MBCs of 2.0 µg/mL and 6.2 ug/mL, respectively. Inhibition at 0.15-2.0 µg of clotrimazole/mL was seen; however, the isolate was not killed at levels >10 µg/mL. The isolate was com- pletely resistant to 5-FC.
Discussion
P. richardsiae is a rare cause of disease in humans. In 1968 Schwartz and Emmons first established it as one of the agents of phaeomycotic cyst. Several other species of dematiaceous fungi can also cause this type of lesion, namely Phialophora gougerotii (Exophiala jeanselmei), Phialophora repens, Wan- giella dermatitidis (formerly Phialophora dermati- tidis), Phialophora spinifera, Phialophora parasit-
ica, Phialophora verrucosa, Phialophora hoffmannii, Phaeoannellomyces elegans, and Phoma species [1-4, 13-20]. Even when the cases of phaeomycotic cyst due to all known agents are considered, this le- sion is rare, and the agents that cause phaeomycotic cyst rarely cause other types of infection. Conversely, other dematiaceous fungi, such as the agents of chro- moblastomycosis, rarely cause phaeomycotic cysts. In the past P. gougerotii (also formerly known as Phialophora jeanselmei and currently named Ex- ophiala jeanselmei) has been the agent most fre- quently reported in association with cases of phae- mycotic cyst. P. richardsiae and other species were usually described in single case reports of phae- mycotic cyst. However, during the past few years reports of P. richardsiae causing this type of infec- tion have outnumbered those of all others.
The reason for the emergence of P. richardsiae is unclear. It may merely reflect a greater interest in reporting cases of phaeomycotic cyst due to this or- ganism than those caused by P. gougerotii, an already established cause of this lesion. In many reported cases of phaemycotic cyst, the etiologic agent was not isolated. Therefore, P. richardsiae may have been commoner than was appreciated. It is also possible that geographic differences may play a role in the increased incidence of these infections. Most of the early reported cases of phaeomycotic cyst were from Europe and tropical regions of the Americas and Africa. Many of the recently reported cases are from the United States, where P. richardsiae may be more prevalent in the environment. Whatever the reason, these recent reports clearly establish P. richardsiae, along with P. gougerotii, as one of the principal causes of phaeomycotic cyst.
Phaeomycotic cyst is one of a variety of diseases caused by the dematiaceous fungi. There have been several systems used to classify these mycoses. Em- mons et al. recognized black piedra, tinea nigra, chro- momycosis, phaeomycotic cyst, mycetoma, and ce- rebral chromomycosis as distinct clinical entities caused by this group of fungi [1]. McGinnis has pro- posed an alternate classification whereby all of the diseases caused by these fungi are divided into two major groups, chromoblastomycosis and phaeohy- phomycosis [3].
Chromoblastomycosis is a cutaneous and subcu- taneous infection characterized by hyperkeratosis and epidermal hyperplasia, intraepidermal microab- scess formation, granulomatous inflammation in the dermis, and the presence of sclerotic bodies. Yeast
and hyphal forms are not seen; the sclerotic bodies may be a vegetative form intermediate between yeast and hyphae.
Phaeohyphomycosis is a group of diseases in which the involved tissues contain yeast forms, hyphae, pseudohyphae, or a combination of these. Sclerotic bodies and grains are not seen. McGinnis further divides this group into superficial, cutane- ous and corneal, subcutaneous, and systemic phaeo- hyphomycoses. Phaeomycotic cyst is a distinct type of subcutaneous phaeohyphomycosis characteris- tically presenting as a solitary, well-encapsulated subcutaneous granuloma with central necrosis. The overlying skin is normal, and there is no regional lymphadenopathy.
The taxonomy of the dematiaceous fungi them- selves has also been an area of great confusion, due, in part, to the fact that many of these fungi display more than one morphologic form in culture and in tissues. The identifying features and classification of this group of fungi have been elucidated by McGinnis [3]. P. richardsiae most closely resembles P. verrucosa, but these species can be differentiated by careful microscopic morphologic examination. The phialides of P. verrucosa are generally short and distinctly urn-shaped, with a broad base and a cup- like collarette. In contrast, P. richardsiae has longer, more slender, tapering phialides that, when mature, terminate in a flat, saucer-shaped collarette (figure 5).
P. richardsiae infections manifested as single dis- tinct subcutaneous nodules in six of the patients reported in the literature. Another patient presented with chronic dacryocystitis. The other two patients had cutaneous involvement and purulent drainage from the ulcerative lesions: one had bone involve- ment, with surrounding granulomatous inflamma- tion, and the other had multiple draining sinuses over the lower one-third of his leg. Both of these atypical presentations occurred in patients with malignancy and probably with accompanying severe immuno- suppression. Therefore, while the particular species of dematiaceous fungi is an important determinant of the clinical syndrome, the immune status of the host is also an important factor. Three patients, in- cluding the patient with adrenocortical carcinoma, had diabetes mellitus. The inability of patients with diabetes mellitus to clear infections with the demati- aceous fungi had been previously observed by others. It is reasonable to conclude that the defects in dia- betes that result in increased susceptibility to other fungal infections, such as candidiasis, are responsi-
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ble for the increased risk of infection with P. richard- siae and other dematiaceous fungi as well. Phaeo- mycotic cysts due to other dematiaceous fungi are also associated with a number of underlying diseases, including malnutrition, carcinoma, hematologic or lymphoreticular malignancy, tuberculosis, leprosy, filariasis, syphilis, schistosomiasis, chronic renal fail- ure, and steroid use, in addition to diabetes mellitus.
The mode of infection with P. richardsiae, as with the other agents of phaeomycotic cysts, is presumed to be subcutaneous inoculation with wood splinters or other contaminated plant material. In the series reported by Ziefer and Connor, six of 25 lesions were found to contain slivers or splinters [4]. These authors concluded that the presence of vegetable ma- terial may be necessary for phaeomycotic cyst for- mation. In experimental animals the inoculation of P. gougerotii without foreign material does not pro- duce infection. However, this model completely ig- nores the significance of host factors in these infec- tions.
Only one of the patients in our review had a splin- ter identified in the lesion. One patient had a punc- ture wound from a thorn, and another received a ste- roid injection for tendonitis of the finger. It is difficult to comprehend how an injection under ster- ile conditions could implant P. richardsiae. It is pos- sible that the organism was already present in the tissues and the steroid injection allowed the infec- tion to progress with formation of a phaeomycotic cyst. Of interest, our patient clearly recalled cutting her foot at age 9 years, 51 years before the develop- ment of a subcutaneous nodule at the same site. We speculate that P. richardsiae was introduced into the tissue at that time, but a clinially apparent infection did not occur until 51 years later, perhaps with reac- tivation occurring as a consequence of her diabetes. These were the only four cases in our review in which an inoculation injury could be substantiated.
The lack of a history of trauma or inoculation in- jury in the majority of patients may be due to a long lag period from the time of the injury to the devel- opment of the lesion. Under these circumstances many patients may not recall a previous injury, es- pecially if the injury was minor. The unusual pre- sentation of chronic dacryocystitis in patient 2 may have been due to inoculation via contaminated plant material that was introduced into the eye, but again this could not be documented by the history presented in the case report.
The diagnosis of infection with P. richardsiae and the other agents of phaeomycotic cysts can be con-
firmed by isolation of the organisms from material obtained by aspiration, incision and drainage, exci- sion, or spontaneous drainage. When specimens for histopathologic examination are available, a char- acteristic pattern is seen. The lesion is in the subcu- taneous tissue and is usually limited by a fibrous cap- sule. There is granulomatous inflammation with giant-cell formation and a central area of necrosis. Hyphal elements were seen in the specimens of all the reported cases of infection with P. richardsiae when the sections were stained with GMS or PAS.
The histopathology of the lesion removed from our patient is shown in figures 4 and 5. Only the le- sions from the two patients with invasive disease had atypical histopathology. The patient with adrenocor- tical carcinoma had dermal and epidermal microab- scesses composed of aggregates of granulocytes and lymphocytes. This type of histologic appearance shares features with chromoblastomycosis. It is un- usual for the agents of phaeomycotic cysts to cause chromoblastomycosis and vice versa, but variable clinical presentations with other species of demati- aceous fungi have been observed. P. verrucosa, for example, is considered an agent of chromoblastomy- cosis, but there is a single report of this organism causing the formation of a phaemycotic cyst [16].
Information regarding the medical management of patients with P. richardsiae and the other demati- aceous fungi is almost completely lacking. Only one patient in the cases reviewed here received antifun- gal therapy. This patient was treated initially with surgical debridement and amphotericin B and later with a course of 5-FC. The lesion resolved 3 weeks after antifungal therapy was discontinued, and it is impossible to determine what effect, if any, the an- tifungal therapy had on the lesion. Chromoblastomy- cosis due to other dematiaceous fungi is frequently reported to respond to 5-FC, which is considered the treatment of choice for this type of infection. How- ever, phaeomycotic cysts are usually treated by exci- sion alone. Some authors have recommended con- comitant therapy with 5-FC, although evidence of benefit is lacking. There is one report of phaeo- mycotic cyst due to P. gougerotii that completely resolved with ketoconazole therapy [21]. Whether this therapy will be effective in other cases of phaeomycotic cyst due to P. gougerotii or other spe- cies of dematiaceous fungi is unknown.
Amphotericin B appears to be the most active agent against P. richardsiae in in vitro susceptibility tests. However, the antifungal susceptibility testing for the dematiaceous fungi is far from standardized,
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and results vary with the size of the inoculum, the age of the primary culture, and the period of obser- vation. Furthermore, as pointed out by Corrado and co-workers, susceptibility testing has traditionally fo- cused on the effects of antifungal agents on spores, but it is the hyphal form that is present in host tis- sues [8]. Until susceptibility testing is standardized, the results of these tests will continue to be of limited value in the management of these infections.
In summary, P. richardsiae infection in humans is rare. The first isolate was recovered from a patient with a phaeomycotic cyst, and recent reports firmly establish P. richardsiae as one of the principal agents of phaeomycotic cyst. Invasive disease is unusual and occurs only in patients who are severely immuno- compromised. Conditions associated with deficient cell-mediated immunity appear to increase the risk of acquiring infection with P. richardsiae, but a nor- mal host may also become infected. The mode of acquisition is probably inoculation with plant ma- terial containing the organism; however, it is not al- ways possible to elicit a history of an inoculation in- jury or to find a retained splinter within the lesion. The histopathology of the lesions in P. richardsiae infection typically consists of granulomatous inflam- mation and the presence of hyphal elements. The specific etiologic diagnosis requires appropriate cul- tures of material obtained by aspiration, incision and drainage, or surgical excision. The lesions usually re- spond to surgical excision, and surgery is currently considered the treatment of choice. However, the role of medical therapy has not been adequately explored. The clinical presentation, risk factors, and response to therapy of infections due to P. richardsiae are simi- lar to those of other agents of phaeomycotic cysts. Further observations, especially in the area of an- tifungal susceptibility testing, are needed to deter- mine whether a specific etiologic diagnosis is impor- tant in the management of these infections.
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