CLINICAL CASE
J Vasc Access 2014 ; 15 ( 4): 321- 324 DOI: 10.5301/jva.5000181
Pyoderma gangrenosum: an exceptional complication of venous access device Sophie La Marca, Gilles Toussoun, Christophe Ho Quoc, Henry Sebban, Emmanuel Delay Department of Plastic and Reconstructive Surgery, Centre Léon Bérard, Lyon - France
ABSTRACT Introduction: Pyoderma gangrenosum (PG) is a rare disease whose precise etiology remains unknown. It causes rapidly developing skin necrosis and can occur after surgery, or after a nonspecific external stimulus. This condition is difficult to diagnose because it often mimics a fulminant infection. Clinical case: We present a case of very significant local presentation of PG after placement of a venous access device. Fifteen days after placement, the patient developed extensive cutaneous ulcers and necrosis in the subclavicular area, which led to the misdiagnosis of infection. The device was removed and the patient was given antibiotics. Because there was no improvement following antibiotic treatment, combined with the worrying and extensive appearance of the skin and extremely intense pain, the diagnosis of PG was made. The patient was immediately treated with high-dose corticosteroids, resulting in rapid improvement of the lesions and relief of pain. Conclusion: PG should be considered in cases of extensive, antibiotic-resistant ulceration and treatment with corticosteroids should be initiated. Clinical improvement is usually dramatic, with almost immediate suppression of the pain and arrest of the lesion’s progression. Early treatment is the best guarantee for an effective recovery. Key words: Pyoderma gangrenosum, Steroid therapy, Venous access device Accepted: July 29, 2013
INTRODUCTION Pyoderma gangrenosum (PG) is a rare disease of the group of neutrophilic dermatoses (1). First described in 1930 by Brunsting and Goeckermann (2), the causative agents were thought to be staphylococci and streptococci. In fact, the exact etiology of PG remains unknown and seems to correspond to an immune dysfunction disorder (3). No diagnostic criteria have been established for PG, only criteria for exclusion of the condition. Infection must firstly be eliminated as a cause of the symptoms. The diagnosis should be considered in the case of rapidly developing lesions (4) and the ineffectiveness of antibiotics. Clinically, this inflammatory skin disease causes rapidly developing skin necrosis. These purely cutaneous lesions start with the development of acneiform pustules or erythematous nodules. The disease progresses to necrotic ulceration, characterized by a very clean edge, hollow at the peak, purple in color and surrounded by a very painful, gently sloping inflammatory bead (5).
One of the characteristic clinical signs is abnormally high pain, which causes the patient to scream at the slightest touch of the wound with a pad or compress. This pain is difficult to control despite carefully monitored analgesic treatment (6). The patients’ psychological state seems to also play a significant role in the occurrence of this disease. Due to the fulminant nature of PG, patients are often very distressed. Hyperthermia is often associated with an increase in inflammatory parameters, which confirms the initial diagnosis of infection. PG may occur or deteriorate following a nonspecific trauma (pathergy), especially after surgery (4). Cases are reported in the literature following abdominal surgery (7, 8) (splenectomy, cholecystectomy and ileostomy), gynecological surgery (9) (hysterectomy) or plastic surgery (breast reduction, breast augmentation or reconstruction and lower limb reconstruction). Cases occurring after trauma, an injection, acupuncture or an insect bite site have also been described. A biopsy should not be systematic, at the risk of further aggravating the lesion. Generally, the histology shows
© 2013 Wichtig Editore - ISSN 1129-7298
321
Pyoderma gangrenosum
a significant infiltration of polynuclear neutrophils in the dermis, edema, thrombosis of small and medium size vessels as well as areas of necrosis and hemorrhage, very suggestive of the diagnosis (10). There is no such thing as a pathognomonic, histological PG lesion. In 50% of the cases, there are associated systemic diseases, especially inflammatory bowel disease (Crohn’s disease and ulcerative colitis) or arthritis (6, 11, 12). Given the frequent association of this diagnosis with systemic diseases, etiological investigation must be carried out based on clinical signs and laboratory analyses. Other more rare diseases have also been associated with PG, such as immune deficiency, leukemia and solid tumors. We report here a case of PG developed at the site of placement of a central venous line. Central venous catheters represent an important development in the administration of medication or fluids, helping to reduce the local complications of chemotherapy, particularly skin necrosis following extravasation from chemotherapy. A similar case has been described in the literature, which resulted in the death of the patient (13). CLINICAL CASE In October 2006, a 69-year-old female patient was admitted to the Oncology Department suffering from pneumonic leiomyosarcoma that required a left pneumonectomy. In 2008, local recurrence made further surgery necessary, with posterior parietal pleurectomy and resection of ribs 5 and 6. She underwent adjuvant radiotherapy in 2009. The appearance of suspected spinal lesions and a second localization on the left leg required chemotherapy and further radiotherapy. In June 2011, pulmonary nodules appeared on the right side. Chemotherapy with trabectedin was prescribed and a venous access device was placed. The procedure was performed under local anesthesia and consisted of placing a tunneled port-a-cath into the right jugular vein, with ultrasound monitoring. The correct position of the device was verified by fluoroscopy, and at the same time we noted the appearance of a hematoma. Chemotherapy with trabectedin was started on the same day the device was placed. In the days following the beginning of chemotherapy at home, we noticed the appearance of an inflammatory area, pain at the site of the venous access device and fever. There was significant inflammation, with an increase in C-reactive protein and the number of leukocytes. Because the infection was suspected to have arisen as a result of the venous access device, it was withdrawn 15 days after initial placement. Treatment with the antibiotics rocephin and vancomycin was started. Local samples were taken and the catheter was sent for bacteriological analysis.
322
Fig. 1 - Suspected pyoderma gangrenosum.
Subsequently, the local condition degraded significantly and uncontrollable pain was reported. The Oncology Department then consulted plastic surgeons for advice. This was 8 days after removal of the device, and 3 weeks into the first chemotherapy treatment. The extravasation of cytotoxic chemotherapy was ruled out after examination by a nurse. On clinical examination, the skin was very much inflamed, with some ulceronecrotic areas extending to the entire right lateral chest area. The patient was in a lot of pain, despite treatment with morphine, and was in a state of anxiety (Fig. 1). Given the extensive ulceronecrotic appearance, the absence of local bacteria, the very intense pain on removing the catheter, together with the state of anxiety, the diagnosis of PG was made. A biopsy was carried out on the edges of the lesion, but did not confirm a formal diagnosis. We found nonspecific, purely dermal inflammatory-type lesions with a common lymphohistiocytic basis. In particular, altered, grouped polynuclear neutrophils were found with purulent and acute inflammation, mainly in the deep part of the sample. We did not find any intravascular thrombosis, or fibroid deposit. There was no visible adnexal structure and lumpy necrotic areas were present. The examination of special stains did not reveal a pathogen on periodic acid Schiff, Grocott and Giemsa staining. Treatment with high-dose corticosteroids (1 mg/kg/day) was initiated, first intravenously, then orally, and was combined with antibiotic treatment. The cutaneous lesion was treated using a fat-based dressing. We regularly reviewed the patient and found a spectacular improvement of the lesions and the rapid disappearance of pain (Fig. 2). Corticosteroids were continued for approximately 8 weeks, with a gradual reduction in dose.
© 2013 Wichtig Editore - ISSN 1129-7298
La Marca et al
Fig. 2 - Evolution of lesions on day 21 of corticosteroid treatment.
The diagnosis was made given the absence of bacteria in samples taken during the removal of the port-a-cath, and in the absence of improvement during antibiotic therapy. Despite a nonspecific biopsy, the diagnosis was made and appropriate treatment implemented. The proposed treatment was high-dose corticosteroids (methylprednisolone 0.5 to 1 mg/kg/day) parenterally, and orally once the lesions are stable, or cyclosporine (5 mg/kg/day) alone or in combination. Clinical improvement is usually dramatic, with almost immediate suppression of pain, no further progression of the lesion and the appearance of granulation tissue (14). The duration of treatment is not standardized and can range from a few weeks to a few months. Corticosteroid treatment is gradually reduced to avoid the risk of skin lesions reappearing. For certain cases of very localized PG that are not associated with systemic diseases, topical treatment is recommended, such as dressings containing corticosteroids or intralesional corticosteroid injections, particularly when immunosuppressive treatment is contraindicated. Thereafter, prevention by corticosteroids is recommended for any trauma. One of the difficulties encountered by the surgeon is to induce immunosuppression when presented with clinical and biological symptoms of infection. Our approach is to combine corticosteroids with antibiotics, while waiting to see how the disease evolves. The goal of treatment is to prevent the progression of ulcers, promote re-epithelialization and decrease pain. With such a presentation of this type of local infection, the first approach for the plastic surgeon could be to excise skin necrosis. A vicious circle would then be set up, with aggravation of the lesion (pathergy) (10) during any trauma (Koebner phenomenon).
Fig. 3 - Final evolution after six weeks of treatment with corticosteroids.
CONCLUSIONS
Immunological assessment for antinuclear antibodies, polynuclear neutrophils, anticytoplasmic antibodies, anticyclic citrullinated peptide antibodies, rheumatoid factors and autoimmune inflammatory bowel disease antibodies was carried out and came back negative. The local remote condition showed skin coverage of satisfactory quality. Cutaneous aftereffects are marked by the presence of telangiectasia (Fig. 3).
PG presents a difficult diagnostic challenge. With an array of rapidly expanding inflammatory and necrotic skin lesions that are resistant to antibiotics, PG should be considered as a differential diagnosis. Early diagnosis is the most important factor in ensuring that patients are treated effectively. Financial support: No financial support to declare.
DISCUSSION
Conflict of interest: The authors declare they have no conflict of interest.
This case illustrates the difficulty of diagnosing PG. The skin lesions and hyperthermia were firstly reported as an infection in the central venous device. The extravasation of cytotoxic chemotherapy was ruled out, following examination by the nurse in charge of its administration.
Address for correspondence: Sophie la Marca 8 rue de l’abondance 69003 Lyon, France [email protected]
© 2013 Wichtig Editore - ISSN 1129-7298
323
Pyoderma gangrenosum
REFERENCES 1. 2. 3.
4.
5.
6.
7.
324
Wallach D. Neutrophilic dermatoses: an overview. Clin Dermatol. 2000;18(3):229-231. Brunsting LA, Goeckermann WE. PG clinical and experi mental observations. Arch Dermatol. 1930;22:655-680. Oka M, Berking C, Nesbit M, et al. Interleukin-8 over expression is present in pyoderma gangrenosum ulcers and leads to ulcer formation in human skin xenografts. Lab Invest. 2000;80(4):595-604. Powell FC, Su WP, Perry HO. Pyoderma gangrenosum: classification and management. J Am Acad Dermatol. 1996;34(3):395-409, quiz 410-412. Jain A, Nanchahal J, Bunker C. Pyoderma gangrenosum occurring in a lower limb fasciocutaneous flap – a lesson to learn. Br J Plast Surg. 2000;53(5):437-440. Su WP, Davis MD, Weenig RH, Powell FC, Perry HO. Pyoderma gangrenosum: clinocopathologic correlation and proposed diagnostic criteria. Int J Dermatol. 2004;43: 790-800. Borlu M, Utaş S. Pyoderma gangrenosum after cho lecystectomy. J Eur Acad Dermatol Venereol. 2001;15(2): 185-186.
8. Patel P, Topilow A. Images in clinical medicine. Atypical pyoderma gangrenosum in a splenectomy incision. N Engl J Med. 2002;347(18):1419. 9. Keohane SG, Graham-Brown RA. Pyoderma gangrenosum complicating hysterectomy for fibroids. Clin Exp Dermatol. 1995;20(6):490-491. 10. Le Huu S, Spertini F, Roggero P, Egloff DV, Raffoul W. Pyoderma gangrenosum: a rare pathology or an omitted diagnosis? Ann Chir Plast. 2009;54(1):82-87. 11. Bennet ML, Jackson JM, Jorizzo JL, Fleischer AB Jr, White WL, Callen JP. Pyoderma gangrenosum. A comparison of typical and atypical forms with an emphasis on time to remission. Case review of 86 patients from 2 institutions. Medicine. 2000;79(1):37-46. 12. Hickman JG, Lazarus GS. Pyoderma gangrenosum: a reappraisal of associated systemic diseases. Br J Dermatol. 1980;102(2):235-237. 13. Inan I, Myers PO, Braun R, Hagen ME, Morel P. Pyoderma gangrenosum after totally implanted central venous access device insertion. World J Surg Oncol. 2008;6(1):31. 14. Viard R, Scevola A, Veber M, Toussoun G, Delay E. Pyoderma gangrenosum: spontaneous healing after early diagnosis. About three cases and general review. Ann Chir Plast Esthet 2013;58(2):146-51.
© 2013 Wichtig Editore - ISSN 1129-7298
J Vasc Access 2014 ; 15 ( 4): 321- 324 DOI: 10.5301/jva.5000181
Pyoderma gangrenosum: an exceptional complication of venous access device Sophie La Marca, Gilles Toussoun, Christophe Ho Quoc, Henry Sebban, Emmanuel Delay Department of Plastic and Reconstructive Surgery, Centre Léon Bérard, Lyon - France
ABSTRACT Introduction: Pyoderma gangrenosum (PG) is a rare disease whose precise etiology remains unknown. It causes rapidly developing skin necrosis and can occur after surgery, or after a nonspecific external stimulus. This condition is difficult to diagnose because it often mimics a fulminant infection. Clinical case: We present a case of very significant local presentation of PG after placement of a venous access device. Fifteen days after placement, the patient developed extensive cutaneous ulcers and necrosis in the subclavicular area, which led to the misdiagnosis of infection. The device was removed and the patient was given antibiotics. Because there was no improvement following antibiotic treatment, combined with the worrying and extensive appearance of the skin and extremely intense pain, the diagnosis of PG was made. The patient was immediately treated with high-dose corticosteroids, resulting in rapid improvement of the lesions and relief of pain. Conclusion: PG should be considered in cases of extensive, antibiotic-resistant ulceration and treatment with corticosteroids should be initiated. Clinical improvement is usually dramatic, with almost immediate suppression of the pain and arrest of the lesion’s progression. Early treatment is the best guarantee for an effective recovery. Key words: Pyoderma gangrenosum, Steroid therapy, Venous access device Accepted: July 29, 2013
INTRODUCTION Pyoderma gangrenosum (PG) is a rare disease of the group of neutrophilic dermatoses (1). First described in 1930 by Brunsting and Goeckermann (2), the causative agents were thought to be staphylococci and streptococci. In fact, the exact etiology of PG remains unknown and seems to correspond to an immune dysfunction disorder (3). No diagnostic criteria have been established for PG, only criteria for exclusion of the condition. Infection must firstly be eliminated as a cause of the symptoms. The diagnosis should be considered in the case of rapidly developing lesions (4) and the ineffectiveness of antibiotics. Clinically, this inflammatory skin disease causes rapidly developing skin necrosis. These purely cutaneous lesions start with the development of acneiform pustules or erythematous nodules. The disease progresses to necrotic ulceration, characterized by a very clean edge, hollow at the peak, purple in color and surrounded by a very painful, gently sloping inflammatory bead (5).
One of the characteristic clinical signs is abnormally high pain, which causes the patient to scream at the slightest touch of the wound with a pad or compress. This pain is difficult to control despite carefully monitored analgesic treatment (6). The patients’ psychological state seems to also play a significant role in the occurrence of this disease. Due to the fulminant nature of PG, patients are often very distressed. Hyperthermia is often associated with an increase in inflammatory parameters, which confirms the initial diagnosis of infection. PG may occur or deteriorate following a nonspecific trauma (pathergy), especially after surgery (4). Cases are reported in the literature following abdominal surgery (7, 8) (splenectomy, cholecystectomy and ileostomy), gynecological surgery (9) (hysterectomy) or plastic surgery (breast reduction, breast augmentation or reconstruction and lower limb reconstruction). Cases occurring after trauma, an injection, acupuncture or an insect bite site have also been described. A biopsy should not be systematic, at the risk of further aggravating the lesion. Generally, the histology shows
© 2013 Wichtig Editore - ISSN 1129-7298
321
Pyoderma gangrenosum
a significant infiltration of polynuclear neutrophils in the dermis, edema, thrombosis of small and medium size vessels as well as areas of necrosis and hemorrhage, very suggestive of the diagnosis (10). There is no such thing as a pathognomonic, histological PG lesion. In 50% of the cases, there are associated systemic diseases, especially inflammatory bowel disease (Crohn’s disease and ulcerative colitis) or arthritis (6, 11, 12). Given the frequent association of this diagnosis with systemic diseases, etiological investigation must be carried out based on clinical signs and laboratory analyses. Other more rare diseases have also been associated with PG, such as immune deficiency, leukemia and solid tumors. We report here a case of PG developed at the site of placement of a central venous line. Central venous catheters represent an important development in the administration of medication or fluids, helping to reduce the local complications of chemotherapy, particularly skin necrosis following extravasation from chemotherapy. A similar case has been described in the literature, which resulted in the death of the patient (13). CLINICAL CASE In October 2006, a 69-year-old female patient was admitted to the Oncology Department suffering from pneumonic leiomyosarcoma that required a left pneumonectomy. In 2008, local recurrence made further surgery necessary, with posterior parietal pleurectomy and resection of ribs 5 and 6. She underwent adjuvant radiotherapy in 2009. The appearance of suspected spinal lesions and a second localization on the left leg required chemotherapy and further radiotherapy. In June 2011, pulmonary nodules appeared on the right side. Chemotherapy with trabectedin was prescribed and a venous access device was placed. The procedure was performed under local anesthesia and consisted of placing a tunneled port-a-cath into the right jugular vein, with ultrasound monitoring. The correct position of the device was verified by fluoroscopy, and at the same time we noted the appearance of a hematoma. Chemotherapy with trabectedin was started on the same day the device was placed. In the days following the beginning of chemotherapy at home, we noticed the appearance of an inflammatory area, pain at the site of the venous access device and fever. There was significant inflammation, with an increase in C-reactive protein and the number of leukocytes. Because the infection was suspected to have arisen as a result of the venous access device, it was withdrawn 15 days after initial placement. Treatment with the antibiotics rocephin and vancomycin was started. Local samples were taken and the catheter was sent for bacteriological analysis.
322
Fig. 1 - Suspected pyoderma gangrenosum.
Subsequently, the local condition degraded significantly and uncontrollable pain was reported. The Oncology Department then consulted plastic surgeons for advice. This was 8 days after removal of the device, and 3 weeks into the first chemotherapy treatment. The extravasation of cytotoxic chemotherapy was ruled out after examination by a nurse. On clinical examination, the skin was very much inflamed, with some ulceronecrotic areas extending to the entire right lateral chest area. The patient was in a lot of pain, despite treatment with morphine, and was in a state of anxiety (Fig. 1). Given the extensive ulceronecrotic appearance, the absence of local bacteria, the very intense pain on removing the catheter, together with the state of anxiety, the diagnosis of PG was made. A biopsy was carried out on the edges of the lesion, but did not confirm a formal diagnosis. We found nonspecific, purely dermal inflammatory-type lesions with a common lymphohistiocytic basis. In particular, altered, grouped polynuclear neutrophils were found with purulent and acute inflammation, mainly in the deep part of the sample. We did not find any intravascular thrombosis, or fibroid deposit. There was no visible adnexal structure and lumpy necrotic areas were present. The examination of special stains did not reveal a pathogen on periodic acid Schiff, Grocott and Giemsa staining. Treatment with high-dose corticosteroids (1 mg/kg/day) was initiated, first intravenously, then orally, and was combined with antibiotic treatment. The cutaneous lesion was treated using a fat-based dressing. We regularly reviewed the patient and found a spectacular improvement of the lesions and the rapid disappearance of pain (Fig. 2). Corticosteroids were continued for approximately 8 weeks, with a gradual reduction in dose.
© 2013 Wichtig Editore - ISSN 1129-7298
La Marca et al
Fig. 2 - Evolution of lesions on day 21 of corticosteroid treatment.
The diagnosis was made given the absence of bacteria in samples taken during the removal of the port-a-cath, and in the absence of improvement during antibiotic therapy. Despite a nonspecific biopsy, the diagnosis was made and appropriate treatment implemented. The proposed treatment was high-dose corticosteroids (methylprednisolone 0.5 to 1 mg/kg/day) parenterally, and orally once the lesions are stable, or cyclosporine (5 mg/kg/day) alone or in combination. Clinical improvement is usually dramatic, with almost immediate suppression of pain, no further progression of the lesion and the appearance of granulation tissue (14). The duration of treatment is not standardized and can range from a few weeks to a few months. Corticosteroid treatment is gradually reduced to avoid the risk of skin lesions reappearing. For certain cases of very localized PG that are not associated with systemic diseases, topical treatment is recommended, such as dressings containing corticosteroids or intralesional corticosteroid injections, particularly when immunosuppressive treatment is contraindicated. Thereafter, prevention by corticosteroids is recommended for any trauma. One of the difficulties encountered by the surgeon is to induce immunosuppression when presented with clinical and biological symptoms of infection. Our approach is to combine corticosteroids with antibiotics, while waiting to see how the disease evolves. The goal of treatment is to prevent the progression of ulcers, promote re-epithelialization and decrease pain. With such a presentation of this type of local infection, the first approach for the plastic surgeon could be to excise skin necrosis. A vicious circle would then be set up, with aggravation of the lesion (pathergy) (10) during any trauma (Koebner phenomenon).
Fig. 3 - Final evolution after six weeks of treatment with corticosteroids.
CONCLUSIONS
Immunological assessment for antinuclear antibodies, polynuclear neutrophils, anticytoplasmic antibodies, anticyclic citrullinated peptide antibodies, rheumatoid factors and autoimmune inflammatory bowel disease antibodies was carried out and came back negative. The local remote condition showed skin coverage of satisfactory quality. Cutaneous aftereffects are marked by the presence of telangiectasia (Fig. 3).
PG presents a difficult diagnostic challenge. With an array of rapidly expanding inflammatory and necrotic skin lesions that are resistant to antibiotics, PG should be considered as a differential diagnosis. Early diagnosis is the most important factor in ensuring that patients are treated effectively. Financial support: No financial support to declare.
DISCUSSION
Conflict of interest: The authors declare they have no conflict of interest.
This case illustrates the difficulty of diagnosing PG. The skin lesions and hyperthermia were firstly reported as an infection in the central venous device. The extravasation of cytotoxic chemotherapy was ruled out, following examination by the nurse in charge of its administration.
Address for correspondence: Sophie la Marca 8 rue de l’abondance 69003 Lyon, France [email protected]
© 2013 Wichtig Editore - ISSN 1129-7298
323
Pyoderma gangrenosum
REFERENCES 1. 2. 3.
4.
5.
6.
7.
324
Wallach D. Neutrophilic dermatoses: an overview. Clin Dermatol. 2000;18(3):229-231. Brunsting LA, Goeckermann WE. PG clinical and experi mental observations. Arch Dermatol. 1930;22:655-680. Oka M, Berking C, Nesbit M, et al. Interleukin-8 over expression is present in pyoderma gangrenosum ulcers and leads to ulcer formation in human skin xenografts. Lab Invest. 2000;80(4):595-604. Powell FC, Su WP, Perry HO. Pyoderma gangrenosum: classification and management. J Am Acad Dermatol. 1996;34(3):395-409, quiz 410-412. Jain A, Nanchahal J, Bunker C. Pyoderma gangrenosum occurring in a lower limb fasciocutaneous flap – a lesson to learn. Br J Plast Surg. 2000;53(5):437-440. Su WP, Davis MD, Weenig RH, Powell FC, Perry HO. Pyoderma gangrenosum: clinocopathologic correlation and proposed diagnostic criteria. Int J Dermatol. 2004;43: 790-800. Borlu M, Utaş S. Pyoderma gangrenosum after cho lecystectomy. J Eur Acad Dermatol Venereol. 2001;15(2): 185-186.
8. Patel P, Topilow A. Images in clinical medicine. Atypical pyoderma gangrenosum in a splenectomy incision. N Engl J Med. 2002;347(18):1419. 9. Keohane SG, Graham-Brown RA. Pyoderma gangrenosum complicating hysterectomy for fibroids. Clin Exp Dermatol. 1995;20(6):490-491. 10. Le Huu S, Spertini F, Roggero P, Egloff DV, Raffoul W. Pyoderma gangrenosum: a rare pathology or an omitted diagnosis? Ann Chir Plast. 2009;54(1):82-87. 11. Bennet ML, Jackson JM, Jorizzo JL, Fleischer AB Jr, White WL, Callen JP. Pyoderma gangrenosum. A comparison of typical and atypical forms with an emphasis on time to remission. Case review of 86 patients from 2 institutions. Medicine. 2000;79(1):37-46. 12. Hickman JG, Lazarus GS. Pyoderma gangrenosum: a reappraisal of associated systemic diseases. Br J Dermatol. 1980;102(2):235-237. 13. Inan I, Myers PO, Braun R, Hagen ME, Morel P. Pyoderma gangrenosum after totally implanted central venous access device insertion. World J Surg Oncol. 2008;6(1):31. 14. Viard R, Scevola A, Veber M, Toussoun G, Delay E. Pyoderma gangrenosum: spontaneous healing after early diagnosis. About three cases and general review. Ann Chir Plast Esthet 2013;58(2):146-51.
© 2013 Wichtig Editore - ISSN 1129-7298
