Australasian Journal of Dermatology (2016) 57, e46–e48
doi: 10.1111/ajd.12302
CASE SERIES
Concurrent pyoderma gangrenosum and infection with Scedosporium apiospermum Dev Tilakaratne, Emma Ryan and Annette Pearce Department of Dermatology, Royal Adelaide Hospital, Adelaide, South Australia, Australia
ABSTRACT We present a patient with pyoderma gangrenosum (PG) following hip surgery, who developed an exacerbation of her ulceration in conjunction with new areas on her lower limbs. Clinically, features of PG and deep fungal infection were apparent. Scedosporium apiospermum was isolated from the ulcers. Key words: deep fungal infection, immunosuppression, pathergy, pyoderma gangrenosum, Scedosporium apiospermum.
INTRODUCTION Scedosporium apiospermum is an emerging pathogen that predominantly infects immunosuppressed individuals.1 Cutaneous infection with this ubiquitous opportunistic organism most commonly causes mycetoma; however, other manifestations including fatal systemic infection, have also been reported.2 We present a case of recurrent ulceration at sites of previously diagnosed pyoderma gangrenosum (PG), from which S. apiospermum was isolated. Although bacterial, viral and other fungal organisms have been reported to cause secondary infection of PG, to our knowledge this is the first reported case of concurrent PG and S. apiospermum infection. We also review reports of fungal infection complicating PG and the relevance of this particular organism. An 88-year-old woman at a private hospital developed clinically and histologically diagnosed PG within days of a
Correspondence: Dr Dev Tilakaratne, Department of Dermatology, Royal Adelaide Hospital, Adelaide, SA 5000, Australia. Email: [email protected] Dev Tilakaratne, MBBS. Emma Ryan, FACD. Annette Pearce, BMBS. Conflict of interest: none Submitted 15 June 2014; accepted 26 November 2014.
Figure 1 Left shin ulceration developing at site of previous ulceration 6 years previously.
left total hip replacement, occurring at the surgical site. Six years previously she had developed chronic ulceration on her left shin after an injury with a garden stake, at the time diagnosed and treated as PG, and which healed after several months. She had a background history of two separate episodes of low-grade non-Hodgkin’s lymphoma in 1976 and 2009, manifesting as cervical lymphadenopathy that were treated with chemotherapy. Computed tomography (CT) surveillance performed 2 months prior to hospital admission was negative. Her left hip lesion was managed by a private dermatologist with i.v. immunoglobulin and i.v. hydrocortisone, and subsequently, oral prednisolone. Healing was slow, heightening concerns over the risk of peri-prosthetic hip infection. Two episodes of acute bleeding peptic ulceration limited the prednisolone dosage, leading to the addition of oral cyclosporine, which caused renal impairment. Mycophenolate mofetil was considered but was withheld, given her gastrointestinal bleeds. Two months after discharge, she was re-admitted with bleeding peptic ulceration. Several days later she developed a left shin ulcer over the site of the previous PG (Fig. 1), attributed to ill-fitting compression stockings. Ulceration over the previous left hip PG site extended and was thought
Abbreviation: PG
pyoderma gangrenosum
© 2015 The Australasian College of Dermatologists
PG or deep fungal infection
e47
Figure 3 Left shin demonstrating new punched out ulcers extruding pus through recently healed ulceration.
Figure 2 Improving ulceration on left shin (top) and left hip (bottom) after 3 days of increased prednisolone dose and continuing cyclosporine and i.v. ceftriaxone.
to be a recurrence. Both ulcers initially enlarged rapidly despite empirical i.v. ceftriaxone, an increase in oral prednisolone from 25 mg to 37.5 mg daily and continued cyclosporine 100 mg twice daily. She remained afebrile and normotensive with stable observations and was transferred to the Royal Adelaide Hospital after 3 days. The large ulcers on her left shin and hip had scattered deep pits, a yellow sloughy, granulating base and undermined violaceous edges. Compared to pretransfer photos, the shin ulcer was improving (Fig. 2), a change attributed to the use of antibiotics and increased prednisolone. There was no lymphadenopathy. Her white cell count was 17.0, with a neutrophilia. She was diagnosed with an exacerbation of PG in light of ill-fitting stockings as a pathergic stimulus and the clinical appearance of PG. Prednisolone was increased to 50 mg daily and cyclosporine to 150 mg twice daily for 3 days. Due to her previous lymphoma and recent renal impairment, cyclosporine was replaced by i.v. Ig 2 g/kg, administered over 3 days. Within days her ulcers demonstrated rapid healing, including partial re-epithelialisation before developing new punched out ulcers extruding frank pus through the re-epithelialised skin (Fig. 3). A culture from pre-transfer swabs yielded S. apiospermum. A histological examination demonstrated a crust of inflammatory cells and serous fluid,
spongiosis and neutrophil exocytosis with intra-epidermal pustules. There were also dermal abscesses with necrosis and suppurative folliculitis. Gomori methenamine. silver and Periodic acid-Schiff-D stains demonstrated irregular fungal hyphae, branched at almost 90-degree angles in the deep dermis. A Gram stain was negative. A tissue culture isolated S. apiospermum. The features were suggestive of concurrent deep fungal infection and PG. She improved within days of commencing a 3-month course of oral voriconazole 200 mg twice daily. She was kept on monthly i.v. Ig and is slowly weaning off prednisolone, experiencing complete healing of the shin and steady improvement of the hip. A whole-body positron emission tomography-CT was suspicious for lymphoma recurrence in the paratracheal nodes and small bowel. Her oncologist has elected to re-image in 3–6 months time due to the likelihood that recurrence will be low grade, given her history. There have been increasing reports of cutaneous infections with S. apiospermum over the past 15 years. In 2013, Boyce and Collins reported a case of sporotrichoid-like lymphocutaneous infection due to S. apiospermum; the first such case in Australia.2 This is the first reported case of PG complicated by S. apiospermum infection. Worldwide, there have been numerous reports of PG-like fungal infections that were initially misdiagnosed as PG, but were due to organisms including Sporothrix schenckii, Cryptococcus spp. and Blastomyces spp., Rhizopus arrhizus and Penicillium marneffei.3–5 The fact that there are numerous reports of such misdiagnoses suggests that the clinical diagnosis of PG is not infallible, and diagnostic accuracy may be increased by utilising histology and microbiology. Many of these articles report on instances where the diagnosis of PG was made clinically, and the diagnosis of a fungal infection was made subsequently on the results of histology or microbiology. Without a histological confirmation of PG in these instances it is most likely that the clinical appearance was due to fungal infection alone. There have been three reports of patients with PG who developed fungal infections at sites separate to the PG location while receiving immunosuppressives. The first was a 46-year-old man with myelodysplastic syndrome with left © 2015 The Australasian College of Dermatologists
e48
D Tilakaratne et al.
facial PG confirmed on clinical and histological grounds, who was maintained with oral prednisolone and dapsone. He developed systemic sepsis with Aspergillus spp. manifesting as bilateral pneumonia, neck abscesses and ulcers on his trunk and limbs.6 Neck abscess aspirates cultured Aspergillus and an ulcer histopathology showed branching septate hyphae. The second was a 66-year-old man with pretibial PG who developed a fungal granuloma on the forearm containing Rhinocladiella atrovirens while on maintenance treatment with oral prednisolone, cyclosporine and mycophenolate mofetil.7 The granuloma resolved with oral voriconazole. The third was a 42-year-old man with a 5-year history of recurrent PG (site not stated) who, after a 12-month remission, developed post-traumatic lower extremity ulcers that were resistant to high-dose oral prednisolone and cyclophosphamide.8 A histology demonstrated acutely branching septate hyphae and fruiting bodies consistent with A. flavus, confirmed by tissue culture. The ulcers healed with surgical debridement, grafting, i.v. amphotericin B and immunosuppressives. In the Australian literature, there have been no reports of concurrent PG with fungal infection. Saracino and colleagues reported 26 cases of PG requiring inpatient management in an Australian tertiary hospital over a 5-year period.9 All 21 patients who had cultures were negative for fungi. Although initially our patient was diagnosed with PG due to ill-fitting stockings, it is more likely that PG and infection with S. apiospermum were occurring concurrently. It is possible that S. apiospermum, being ubiquitous in soil, was inoculated into the left shin at the time of garden stake injury several years previously, and that the recent combination of immunosuppression, lymphoma and her age allowed this organism to express its pathogenic potential. A review of demographic and clinical findings in 20 patients with cutaneous fungal infections with S. apiospermum found that 18 were immunocompromised either through medication or leukaemia and eight died, four of whom had only limited cutaneous disease at presentation.1 Variable resistance of S. apiospermum to itraconazole and amphotericin B has been reported, whereas in vitro and in vivo studies demonstrate excellent response to voriconazole.10
© 2015 The Australasian College of Dermatologists
CONCLUSION This case reminds us that a diagnosis of PG does not exclude an infective component, and that fungal infection may be coexistent. Australian dermatologists must be aware of S. apiospermum as an emerging pathogen with the potential for overwhelming infection, particularly in immunosuppressed individuals. Early treatment with voriconazole is recommended.
REFERENCES 1.
2.
3.
4.
5.
6.
7. 8.
9.
10.
Uenotsuchi T, Moroi Y, Urabe K et al. Cutaneous Scedosporium apiospermum infection an immunocompromised patient and a review of the literature. Acta Derm. Venereol. 2005; 85: 156–9. Boyce Z, Collins N. Scedosporium apiospermum: an unreported cause of fungal sporotrichoid-like lymphocutaneous infection in Australia and a review of the literature. Australas. J. Dermatol. 2013; doi: 10.1111/ajd.12119. [Epub ahead of print]. Weenig RH, Davis MDP, Dahl PR et al. Skin ulcers misdiagnosed as pyoderma gangrenosum. N. Engl. J. Med. 2002; 347: 1412–8. Lysy J, Zimmerman J, Ackerman Z et al. Atypical auricular pyoderma gangrenosum simulating fungal infection. J. Clin. Gastroenterol. 1989; 11: 561–4. Kerr OA, Bong C, Wallis C et al. Primary cutaneous mucormycosis masquerading as pyoderma gangrenosum (Correspondence). Br. J. Dermatol. 2004; 150: 1212–34. Yang C-C, Hsu P-C, Cheng C-W et al. Coexistence of fatal disseminated invasive Aspergillosis and pyoderma gangrenosum: a case report. Med. Princ. Pract. 2011; 20: 380–3. Tai YJ, Kelly R. Pyoderma gangrenosum complicated by herpes simplex virus infection. Australas. J. Dermatol. 2005; 46: 161–4. Harmon CB, Daniel Su WP, Peters MS. Cutaneous Aspergillosis complicating pyoderma gangrenosum. J. Am. Acad. Dermatol. 1993; 29: 656–8. Saracino A, Kelly R, Liew D et al. Pyoderma gangrenosum requiring inpatient management: a report of 26 cases with follow up. Australas. J. Dermatol. 2011; 52: 218–21. Yu Z, Hu L, Jiang M et al. Dermatic Scedosporium apiospermum infection after autologous bone marrow transplantation. Intern. Med. 2013; 52: 689–93.
doi: 10.1111/ajd.12302
CASE SERIES
Concurrent pyoderma gangrenosum and infection with Scedosporium apiospermum Dev Tilakaratne, Emma Ryan and Annette Pearce Department of Dermatology, Royal Adelaide Hospital, Adelaide, South Australia, Australia
ABSTRACT We present a patient with pyoderma gangrenosum (PG) following hip surgery, who developed an exacerbation of her ulceration in conjunction with new areas on her lower limbs. Clinically, features of PG and deep fungal infection were apparent. Scedosporium apiospermum was isolated from the ulcers. Key words: deep fungal infection, immunosuppression, pathergy, pyoderma gangrenosum, Scedosporium apiospermum.
INTRODUCTION Scedosporium apiospermum is an emerging pathogen that predominantly infects immunosuppressed individuals.1 Cutaneous infection with this ubiquitous opportunistic organism most commonly causes mycetoma; however, other manifestations including fatal systemic infection, have also been reported.2 We present a case of recurrent ulceration at sites of previously diagnosed pyoderma gangrenosum (PG), from which S. apiospermum was isolated. Although bacterial, viral and other fungal organisms have been reported to cause secondary infection of PG, to our knowledge this is the first reported case of concurrent PG and S. apiospermum infection. We also review reports of fungal infection complicating PG and the relevance of this particular organism. An 88-year-old woman at a private hospital developed clinically and histologically diagnosed PG within days of a
Correspondence: Dr Dev Tilakaratne, Department of Dermatology, Royal Adelaide Hospital, Adelaide, SA 5000, Australia. Email: [email protected] Dev Tilakaratne, MBBS. Emma Ryan, FACD. Annette Pearce, BMBS. Conflict of interest: none Submitted 15 June 2014; accepted 26 November 2014.
Figure 1 Left shin ulceration developing at site of previous ulceration 6 years previously.
left total hip replacement, occurring at the surgical site. Six years previously she had developed chronic ulceration on her left shin after an injury with a garden stake, at the time diagnosed and treated as PG, and which healed after several months. She had a background history of two separate episodes of low-grade non-Hodgkin’s lymphoma in 1976 and 2009, manifesting as cervical lymphadenopathy that were treated with chemotherapy. Computed tomography (CT) surveillance performed 2 months prior to hospital admission was negative. Her left hip lesion was managed by a private dermatologist with i.v. immunoglobulin and i.v. hydrocortisone, and subsequently, oral prednisolone. Healing was slow, heightening concerns over the risk of peri-prosthetic hip infection. Two episodes of acute bleeding peptic ulceration limited the prednisolone dosage, leading to the addition of oral cyclosporine, which caused renal impairment. Mycophenolate mofetil was considered but was withheld, given her gastrointestinal bleeds. Two months after discharge, she was re-admitted with bleeding peptic ulceration. Several days later she developed a left shin ulcer over the site of the previous PG (Fig. 1), attributed to ill-fitting compression stockings. Ulceration over the previous left hip PG site extended and was thought
Abbreviation: PG
pyoderma gangrenosum
© 2015 The Australasian College of Dermatologists
PG or deep fungal infection
e47
Figure 3 Left shin demonstrating new punched out ulcers extruding pus through recently healed ulceration.
Figure 2 Improving ulceration on left shin (top) and left hip (bottom) after 3 days of increased prednisolone dose and continuing cyclosporine and i.v. ceftriaxone.
to be a recurrence. Both ulcers initially enlarged rapidly despite empirical i.v. ceftriaxone, an increase in oral prednisolone from 25 mg to 37.5 mg daily and continued cyclosporine 100 mg twice daily. She remained afebrile and normotensive with stable observations and was transferred to the Royal Adelaide Hospital after 3 days. The large ulcers on her left shin and hip had scattered deep pits, a yellow sloughy, granulating base and undermined violaceous edges. Compared to pretransfer photos, the shin ulcer was improving (Fig. 2), a change attributed to the use of antibiotics and increased prednisolone. There was no lymphadenopathy. Her white cell count was 17.0, with a neutrophilia. She was diagnosed with an exacerbation of PG in light of ill-fitting stockings as a pathergic stimulus and the clinical appearance of PG. Prednisolone was increased to 50 mg daily and cyclosporine to 150 mg twice daily for 3 days. Due to her previous lymphoma and recent renal impairment, cyclosporine was replaced by i.v. Ig 2 g/kg, administered over 3 days. Within days her ulcers demonstrated rapid healing, including partial re-epithelialisation before developing new punched out ulcers extruding frank pus through the re-epithelialised skin (Fig. 3). A culture from pre-transfer swabs yielded S. apiospermum. A histological examination demonstrated a crust of inflammatory cells and serous fluid,
spongiosis and neutrophil exocytosis with intra-epidermal pustules. There were also dermal abscesses with necrosis and suppurative folliculitis. Gomori methenamine. silver and Periodic acid-Schiff-D stains demonstrated irregular fungal hyphae, branched at almost 90-degree angles in the deep dermis. A Gram stain was negative. A tissue culture isolated S. apiospermum. The features were suggestive of concurrent deep fungal infection and PG. She improved within days of commencing a 3-month course of oral voriconazole 200 mg twice daily. She was kept on monthly i.v. Ig and is slowly weaning off prednisolone, experiencing complete healing of the shin and steady improvement of the hip. A whole-body positron emission tomography-CT was suspicious for lymphoma recurrence in the paratracheal nodes and small bowel. Her oncologist has elected to re-image in 3–6 months time due to the likelihood that recurrence will be low grade, given her history. There have been increasing reports of cutaneous infections with S. apiospermum over the past 15 years. In 2013, Boyce and Collins reported a case of sporotrichoid-like lymphocutaneous infection due to S. apiospermum; the first such case in Australia.2 This is the first reported case of PG complicated by S. apiospermum infection. Worldwide, there have been numerous reports of PG-like fungal infections that were initially misdiagnosed as PG, but were due to organisms including Sporothrix schenckii, Cryptococcus spp. and Blastomyces spp., Rhizopus arrhizus and Penicillium marneffei.3–5 The fact that there are numerous reports of such misdiagnoses suggests that the clinical diagnosis of PG is not infallible, and diagnostic accuracy may be increased by utilising histology and microbiology. Many of these articles report on instances where the diagnosis of PG was made clinically, and the diagnosis of a fungal infection was made subsequently on the results of histology or microbiology. Without a histological confirmation of PG in these instances it is most likely that the clinical appearance was due to fungal infection alone. There have been three reports of patients with PG who developed fungal infections at sites separate to the PG location while receiving immunosuppressives. The first was a 46-year-old man with myelodysplastic syndrome with left © 2015 The Australasian College of Dermatologists
e48
D Tilakaratne et al.
facial PG confirmed on clinical and histological grounds, who was maintained with oral prednisolone and dapsone. He developed systemic sepsis with Aspergillus spp. manifesting as bilateral pneumonia, neck abscesses and ulcers on his trunk and limbs.6 Neck abscess aspirates cultured Aspergillus and an ulcer histopathology showed branching septate hyphae. The second was a 66-year-old man with pretibial PG who developed a fungal granuloma on the forearm containing Rhinocladiella atrovirens while on maintenance treatment with oral prednisolone, cyclosporine and mycophenolate mofetil.7 The granuloma resolved with oral voriconazole. The third was a 42-year-old man with a 5-year history of recurrent PG (site not stated) who, after a 12-month remission, developed post-traumatic lower extremity ulcers that were resistant to high-dose oral prednisolone and cyclophosphamide.8 A histology demonstrated acutely branching septate hyphae and fruiting bodies consistent with A. flavus, confirmed by tissue culture. The ulcers healed with surgical debridement, grafting, i.v. amphotericin B and immunosuppressives. In the Australian literature, there have been no reports of concurrent PG with fungal infection. Saracino and colleagues reported 26 cases of PG requiring inpatient management in an Australian tertiary hospital over a 5-year period.9 All 21 patients who had cultures were negative for fungi. Although initially our patient was diagnosed with PG due to ill-fitting stockings, it is more likely that PG and infection with S. apiospermum were occurring concurrently. It is possible that S. apiospermum, being ubiquitous in soil, was inoculated into the left shin at the time of garden stake injury several years previously, and that the recent combination of immunosuppression, lymphoma and her age allowed this organism to express its pathogenic potential. A review of demographic and clinical findings in 20 patients with cutaneous fungal infections with S. apiospermum found that 18 were immunocompromised either through medication or leukaemia and eight died, four of whom had only limited cutaneous disease at presentation.1 Variable resistance of S. apiospermum to itraconazole and amphotericin B has been reported, whereas in vitro and in vivo studies demonstrate excellent response to voriconazole.10
© 2015 The Australasian College of Dermatologists
CONCLUSION This case reminds us that a diagnosis of PG does not exclude an infective component, and that fungal infection may be coexistent. Australian dermatologists must be aware of S. apiospermum as an emerging pathogen with the potential for overwhelming infection, particularly in immunosuppressed individuals. Early treatment with voriconazole is recommended.
REFERENCES 1.
2.
3.
4.
5.
6.
7. 8.
9.
10.
Uenotsuchi T, Moroi Y, Urabe K et al. Cutaneous Scedosporium apiospermum infection an immunocompromised patient and a review of the literature. Acta Derm. Venereol. 2005; 85: 156–9. Boyce Z, Collins N. Scedosporium apiospermum: an unreported cause of fungal sporotrichoid-like lymphocutaneous infection in Australia and a review of the literature. Australas. J. Dermatol. 2013; doi: 10.1111/ajd.12119. [Epub ahead of print]. Weenig RH, Davis MDP, Dahl PR et al. Skin ulcers misdiagnosed as pyoderma gangrenosum. N. Engl. J. Med. 2002; 347: 1412–8. Lysy J, Zimmerman J, Ackerman Z et al. Atypical auricular pyoderma gangrenosum simulating fungal infection. J. Clin. Gastroenterol. 1989; 11: 561–4. Kerr OA, Bong C, Wallis C et al. Primary cutaneous mucormycosis masquerading as pyoderma gangrenosum (Correspondence). Br. J. Dermatol. 2004; 150: 1212–34. Yang C-C, Hsu P-C, Cheng C-W et al. Coexistence of fatal disseminated invasive Aspergillosis and pyoderma gangrenosum: a case report. Med. Princ. Pract. 2011; 20: 380–3. Tai YJ, Kelly R. Pyoderma gangrenosum complicated by herpes simplex virus infection. Australas. J. Dermatol. 2005; 46: 161–4. Harmon CB, Daniel Su WP, Peters MS. Cutaneous Aspergillosis complicating pyoderma gangrenosum. J. Am. Acad. Dermatol. 1993; 29: 656–8. Saracino A, Kelly R, Liew D et al. Pyoderma gangrenosum requiring inpatient management: a report of 26 cases with follow up. Australas. J. Dermatol. 2011; 52: 218–21. Yu Z, Hu L, Jiang M et al. Dermatic Scedosporium apiospermum infection after autologous bone marrow transplantation. Intern. Med. 2013; 52: 689–93.
