- Email: [email protected]
Wet gangrene in hemodialysis patients with calciphylaxisis is associated with a poor prognosis
PII: S0967-2109(01)00084-9
Cardiovascular Surgery, Vol. 9, No. 6, pp. 565–570, 2001 2001 The International Society for Cardiovascular Surgery Published by Elsevier Science Ltd. All rights reserved 0967-2109/01 $20.00
www.elsevier.com/locate/cardiosur
Wet gangrene in hemodialysis patients with calciphylaxisis is associated with a poor prognosis Catharina A. Davis and R. James Valentine Division of Vascular Surgery, Department of Surgery, The University of Texas Southwestern Medical Center, Dallas, TX 75235-9031, USA Calciphylaxis is a rare syndrome characterized by progressive vascular calcification and ischemic tissue loss in patients with chronic renal failure. We report our five-year experience with five patients who developed foot gangrene due to calciphylaxis. All five patients had characteristic clinical, laboratory, and radiologic findings of the disorder, but no diagnostic variable was uniformly present. All five had progressed to advanced gangrene at the time of surgical consultation. Despite aggressive local attempts to control infection, all five patients died of septic complications. Parathyroidectomy was performed in three patients but did not alter the course in any case. This small experience suggests that the outcome of foot gangrene associated with calciphylaxis is predicated on the degree of tissue loss. Aggressive local wound care does not appear to be adequate to control infection in patients who have already developed gangrene. Although parathyroidectomy may have important long-term advantages in patients with calciphylaxis, it does not appear to affect outcome in these advanced cases. 2001 The International Society for Cardiovascular Surgery. Published by Elsevier Science Ltd. All rights reserved Keywords: calciphylaxis, end stage renal disease, foot gangrene
Introduction The onset of advanced foot ischemia in a patient with end stage renal disease (ESRD) and widespread tissue calcification portends a dismal prognosis. Previous studies have documented a reduced limb salvage rate after revascularization in patients with ESRD [1], but the combination of advanced gangrene, severe medial calcinosis, and ESRD appears to be particularly morbid. This combination has been termed ‘calciphylaxis’ to reflect the metastatic soft tissue calcification commonly seen in these patients. Affected individuals present with skin lesions localized to the distal forefoot which then progress to gangrene. Previous reports based on small series of patients with calciphylaxis have documented high
Correspondence to: R. James Valentine, M.D. Tel.: +1-214-6483514; Fax: +1-214-648-2790; e-mail: [email protected]
CARDIOVASCULAR SURGERY
DECEMBER 2001 VOL 9 NO 6
rates of major amputation and mortality associated with this disorder [2]. The diagnosis of calciphylaxis is not always clear. It should be suspected in a patient with ESRD who presents with advanced distal foot ischemia or tissue loss, especially if pedal pulses are present [3]. A number of clinical and laboratory findings may accompany these symptoms and skin punch biopsy may show characteristic findings. Treatment consists of aggressive wound care or amputation to control sepsis. Parathyroidectomy has also been recommended for definitive treatment of calciphylaxis and has been reported to improve wound healing in advanced cases [4]. We report the outcome of five patients with forefoot tissue loss due to calciphylaxis who presented to our vascular surgery service.
Methods The five patients were referred to our vascular surgery service between 1994 and 1999. This group 565
Wet gangrene in hemodialysis patients: C. A. Davis and R. J. Valentine
represents all patients who met the diagnostic criteria for calciphylaxis at our institutions during the study period (Table 1). Medical records were scrutinized to determine demographics; cause of ESRD; comorbid conditions; method and duration of dialysis; serum calcium, phosphorus, and parathyroid hormone (PTH) levels; peripheral vascular symptoms; and physical findings. All available radiographic studies and noninvasive vascular tests were reviewed. Therapeutic interventions and outcome were carefully documented.
Results The mean age of the five study patients (two men, three women) was 38±14 yr. All patients were on hemodialysis for a mean of 3.7±3 yr. ESRD was attributed to diabetes and hypertension in two, to systemic lupus erythematosis (SLE) in two, and to hypertension in one. One patient had a history of chronic atrial fibrillation, and one had a history of deep venous thrombosis. A summary of patient characteristics is shown in Table 2. The five patients presented to the hospital with tissue loss involving the distal legs and feet. Three patients had nonhealing ulcers, and two had dry gangrene at initial presentation. Tissue loss was bilateral in all patients. Ulcers appeared to be arterial in origin and were located on the anterior ankles and on the dorsal foot surfaces. Gangrene involved the distal third of the forefeet in two patients (Figure 1). Severe skin mottling accompanied the tissue loss in all five patients (livedo reticularis). All five patients had progression of their ischemic lesions in the hospital. At the time of vascular surgery consultation, four of the five had already progressed to wet gangrene, and two had clinical signs of sepsis. Palpable pulses or normal (triphasic) Doppler signals were obtained in the pedal arteries of all five patients (Table 2). None of the patients had upper extremity involvement. The mean calcium–phosphorus product (Ca–PO4, normal range <70) among the five patients was 77±52 (range, 12–143), and three had Ca–PO4 >60. Table 1
Characteristic features of calciphylaxis
Physical exam Distal acral gangrene Palpable distal pulses X-ray Vascular calcifications Laboratory studies Hyperparathyroidism (elevated PTHa) Calcium–phosphorus product >60 Skin punch biopsy Epidermal necrosis Dermal inflammatory infiltrates Medial calcifications a
PTH=parathyroid hormone level
566
The mean PTH level was 629±536 pg/ml (normal 120–240), and four of the five had levels above the normal range. Foot radiographs were available for four of the five patients, all of which demonstrated extensive vascular calcifications involving the distal tibial and pedal arterial segments (Figure 2). All five patients underwent diagnostic punch biopsies of the affected skin, which demonstrated epidermal necrosis, dermal inflammatory infiltrates, and medial calcifications characteristic of calciphylaxis (Figure 3). Aggressive wound care was instituted immediately in all five patients. This included multiple incisions and debridements followed by hydrotherapy and application of skin grafts when feasible. All five patients underwent at least two surgical debridements, and two patients had five operations. The four patients with wet gangrene had rapid progression of tissue loss despite aggressive wound care and expired due to complications of sepsis. The fifth patient had dry gangrene on initial presentation. Amputation below the knee was recommended, but the patient refused. Urgent, bilateral above-knee amputations were eventually performed after the patient developed sepsis, but she ultimately succumbed to diffuse coagulopathy with hemorrhagic shock three weeks later. Subtotal parathyroidectomy was performed in three of the five patients to improve the potential for wound healing and survival as suggested by others [5]. Two patients did not have parathyroidectomy because of sepsis. Parathyroidectomy was performed in the other three at variable intervals during hospitalization when foot infections appeared to be under control. Parathyroidectomy did not delay amputation in any case. However, all three patients had progression of wet gangrene despite parathyroidectomy, and all three died of septic complications.
Discussion Calciphylaxis occurs most commonly in patients with ESRD and secondary hyperparathyroidism. Fortunately, calciphylaxis is rare, affecting less than 1% of patients with both disorders. The exact mechanism of tissue loss in patients with calciphylaxis remains unknown. The underlying pathophysiology has been attributed to widespread deposition of calcium in small arteries of the lower extremity, leading to progressive luminal encroachment and ischemia. While medial calcification seen in skin biopsy specimens provides some evidence that primary calcium deposition may be the initiating step in the development of calciphylaxis, the universal presence of dermal inflammatory infiltration suggest that there may be an additional inflammatory component. One of our five patients with biopsy-proved calciphylaxis did not have an elevated PTH level. At necropsy, this CARDIOVASCULAR SURGERY
DECEMBER 2001 VOL 9 NO 6
CARDIOVASCULAR SURGERY
F
M
M
F F
23
DECEMBER 2001 VOL 9 NO 6
49
55
26 38
ESRD, HTN, SLE ESRD, HTN, IDDM
ESRD, HTN, atrial fib
ESRD, SLE, HTN seizures ESRD, HTN, NIDDM
D/P
Wet gangrene BLE Wet gangrene BLE
Wet gangrene BLE
Wet gangrene BLE
D D
D
P
Dry gangrene both feet P
Physical exam
92 12
39
80–100
143
556 40
847
280
1420
Diagnostics PTH CaXPO4
Patient care
X-ray and Punch biopsy Wound care, amputation, parathryoidectomy X-ray and Punch biopsy Wound care, debridement, parathyroidectomy X-ray and Punch biopsy Wound care, debridement, parathyroidectomy Punch biopsy Local wound care X-ray and post mortem Local wound care exam
X-ray or biopsy
Sepsis, death Sepsis, death
Sepsis, death
Sepsis, death
Coagulopathy, sepsis, death
Outcome
a ESRD: end stage renal disease; SLE: systemic lupus erythematosus; HTN: hypertension; NIDDM: noninsulin dependent diabetes mellitus; BLE: bilateral lower extremities; IDDM: insulin dependent diabetes mellitus; CHF: congestive heart failure; DVT: deep vein thrombosis; P: palpable pedal pulse; D: Doppler signal only
B W
B
B
B
Past medical history
Sex
Age
Race
Summary of patient characteristicsa
Table 2
Wet gangrene in hemodialysis patients: C. A. Davis and R. J. Valentine
567
Wet gangrene in hemodialysis patients: C. A. Davis and R. J. Valentine
Figure 1 Distal forefoot gangrene in a patient with calciphylaxis
Figure 2 Foot radiograph demonstrating extensive calcification of the posterior tibial and plantar arteries
patient proved to have widespread tissue calcification involving multiple organs. This suggests that other mechanisms besides secondary hyperparathyroidism may be responsible for calcium deposition. Accordingly, the incidence of calciphylaxis may be higher than previously suspected in groups of patients with ESRD. 568
The distribution of cutaneous necrosis is highly variable. In addition to acral lesions, previous reports have documented involvement of the proximal leg, fingers, abdominal wall, and penis [5–7]. It appears that the distal feet and toes represent the most common site of involvement, but a number of patients with involvement in other areas may have been diagCARDIOVASCULAR SURGERY
DECEMBER 2001 VOL 9 NO 6
Wet gangrene in hemodialysis patients: C. A. Davis and R. J. Valentine
Figure 3 Punch biopsy of an acral ulcer in a patient with calciphylaxis showing typical medial calcification
nosed incorrectly. Our experience had centered on acral gangrene. None of the patients in the present series had involvement of the thigh, abdominal wall, or upper extremity, so we are unable to comment on the proper management of these lesions. Others have shown that aggressive wound care and digital amputations, combined with timely parathyroidectomy, may lead to significant improvement in many cases [5–9]. Parathyroidectomy has been suggested as the single most important intervention in the long-term treatment of patients with calciphylaxis [5–9]. However, parathyroidectomy had little impact on the outcome of our small group of patients. We suspect that the difference in outcome between patients in our study and the previous reports is associated with the advanced degree of tissue loss in our patients. In the present study, the majority of patients had already progressed to wet gangrene with impending sepsis at the time of surgical consultation. Despite aggressive wound care, these patients progressed rapidly to overwhelming infection and death. Based on the experience of others, we speculate that our patients did not receive parathyroidectomy early enough to reverse changes associated with calciphylaxis. Our small experience suggests that parathyroidectomy does not improve the survival or wound healing potential of patients with calciphylaxis who have already progressed to wet gangrene. We believe that we missed the opportunity to salCARDIOVASCULAR SURGERY
DECEMBER 2001 VOL 9 NO 6
vage the five patients in this study with timely amputations. All five patients in this series were admitted to general medical services with consultations requested from physical medicine, general surgery and vascular services. We feel that the delay in definitive care of these patients was probably due to delay in consulting surgical services. All five patients had developed advanced tissue loss by the time of surgical consultation, and all five expired due to complications of uncontrolled sepsis, despite multiple surgical debridements and aggressive wound care. This suggests that control of sepsis is paramount in patients with advanced complications of calciphylaxis. The decision for amputation is clearly based on individual circumstances, but our experience suggests that local wound care is not adequate therapy in advanced cases of tissue loss due to calciphylaxis. While it would have been desirable to treat the wounds in the early stages, before ischemia progressed to wet gangrene, we were not afforded this opportunity. In fact, parathyroidectomy may have had significant benefit in healing open wounds in the earlier stages. Accordingly, we advocate early referral of these patients to the surgeon to ensure timely wound care and prevention of infection. We consider the onset of advanced gangrene, particularly if associated with infection, as an indication for primary amputation. We acknowledge that there are significant limitations with this study. Because it is retrospective in 569
Wet gangrene in hemodialysis patients: C. A. Davis and R. J. Valentine
nature, a number of patients with calciphylaxis who had a more favorable outcome may have been missed. Specifically, some patients with minimal tissue loss may not have been seen by the surgery service. It is unlikely that any patient with infectious complications requiring operative debridement would have been missed, although some requiring minimal debridement at the bedside may have gone undetected. However, including additional patients with less advanced ischemia would not have altered our conclusions that outcome is largely affected by the onset of superimposed sepsis. Patients with less extensive tissue loss may benefit from parathyroidectomy, but our data suggest that patients with wet gangrene tend to suffer early deaths, before any long term benefit can be achieved. In summary, our experience with five patients who had advanced forefoot ischemia due to calciphylaxis suggests that early outcome is predicated on the degree of tissue loss. Aggressive wound care does not appear to be adequate to control infection in patients who have already developed gangrene. Our limited experience suggests that major amputations are indicated in these circumstances. Although parathyroidectomy may have important long-term advantages, it does not appear to affect outcome in these advanced cases.
570
References 1. Johnson, B. L., Glickman, M. D., Bandyk, D. F. et al., Failure of foot salvage in patients with end-stage renal disease after surgical revascularization. Journal of Vascular Surgery, 1995, 22, 280–286. 2. Androgue, J. H., Frazier, M. R., Zeloff, B. et al., Systemic calcinosis revisited. American Journal of Nephrology, 1981, 1, 175– 183. 3. Angelis, M., Wong, L. L., Myers, S. et al., Calciphylaxis in patients on hemodialysis: a prevalence study. Surgery, 1997, 122, 1083–1090. 4. Dereure, O., Leray, H., Barneon, G. et al., Extensive necrotizing livedo reticularis in a patient with chronic renal failure, hyperparathyroidism, and coagulation disorder: regression after subtotal parathyroidectomy. Dermatology, 1996, 192, 167–170. 5. Duh, Q. Y., Lim, R. C. and Clark, O. H., Calciphylaxis in secondary hyperparathyroidism. Archives of Surgery, 1991, 7, 1213–1218. 6. Coates, T., Kirkland, G. S., Dymock, R. B. et al., Cutaneous necrosis from calcific uremic arteriopathy. American Journal of Kidney Disease, 1998, 32, 384–391. 7. Bleyer, A. J., Choi, M., Igwemezie, B. et al., A case control study of proximal calciphylaxis. American Journal of Kidney Disease, 1998, 32, 376–383. 8. Hafner, J., Keusch, G., Wahl, C. et al., Uremic small-artery disease with medial calcification and intimal hyperplasia (so-called calciphylaxis): a complication of chronic renal failue and benefit from parathyroidectomy. Journal of the American Academy of Dermatology, 1995, 33, 954–962. 9. Skinner, K. A. and Zuckerbraun, L., Recurrent secondary hyperparathyroidism (an argument for total parathyroidectomy). Archives of Surgery, 1996, 131, 724–727. Paper accepted 1 May 2001
CARDIOVASCULAR SURGERY
DECEMBER 2001 VOL 9 NO 6
Cardiovascular Surgery, Vol. 9, No. 6, pp. 565–570, 2001 2001 The International Society for Cardiovascular Surgery Published by Elsevier Science Ltd. All rights reserved 0967-2109/01 $20.00
www.elsevier.com/locate/cardiosur
Wet gangrene in hemodialysis patients with calciphylaxisis is associated with a poor prognosis Catharina A. Davis and R. James Valentine Division of Vascular Surgery, Department of Surgery, The University of Texas Southwestern Medical Center, Dallas, TX 75235-9031, USA Calciphylaxis is a rare syndrome characterized by progressive vascular calcification and ischemic tissue loss in patients with chronic renal failure. We report our five-year experience with five patients who developed foot gangrene due to calciphylaxis. All five patients had characteristic clinical, laboratory, and radiologic findings of the disorder, but no diagnostic variable was uniformly present. All five had progressed to advanced gangrene at the time of surgical consultation. Despite aggressive local attempts to control infection, all five patients died of septic complications. Parathyroidectomy was performed in three patients but did not alter the course in any case. This small experience suggests that the outcome of foot gangrene associated with calciphylaxis is predicated on the degree of tissue loss. Aggressive local wound care does not appear to be adequate to control infection in patients who have already developed gangrene. Although parathyroidectomy may have important long-term advantages in patients with calciphylaxis, it does not appear to affect outcome in these advanced cases. 2001 The International Society for Cardiovascular Surgery. Published by Elsevier Science Ltd. All rights reserved Keywords: calciphylaxis, end stage renal disease, foot gangrene
Introduction The onset of advanced foot ischemia in a patient with end stage renal disease (ESRD) and widespread tissue calcification portends a dismal prognosis. Previous studies have documented a reduced limb salvage rate after revascularization in patients with ESRD [1], but the combination of advanced gangrene, severe medial calcinosis, and ESRD appears to be particularly morbid. This combination has been termed ‘calciphylaxis’ to reflect the metastatic soft tissue calcification commonly seen in these patients. Affected individuals present with skin lesions localized to the distal forefoot which then progress to gangrene. Previous reports based on small series of patients with calciphylaxis have documented high
Correspondence to: R. James Valentine, M.D. Tel.: +1-214-6483514; Fax: +1-214-648-2790; e-mail: [email protected]
CARDIOVASCULAR SURGERY
DECEMBER 2001 VOL 9 NO 6
rates of major amputation and mortality associated with this disorder [2]. The diagnosis of calciphylaxis is not always clear. It should be suspected in a patient with ESRD who presents with advanced distal foot ischemia or tissue loss, especially if pedal pulses are present [3]. A number of clinical and laboratory findings may accompany these symptoms and skin punch biopsy may show characteristic findings. Treatment consists of aggressive wound care or amputation to control sepsis. Parathyroidectomy has also been recommended for definitive treatment of calciphylaxis and has been reported to improve wound healing in advanced cases [4]. We report the outcome of five patients with forefoot tissue loss due to calciphylaxis who presented to our vascular surgery service.
Methods The five patients were referred to our vascular surgery service between 1994 and 1999. This group 565
Wet gangrene in hemodialysis patients: C. A. Davis and R. J. Valentine
represents all patients who met the diagnostic criteria for calciphylaxis at our institutions during the study period (Table 1). Medical records were scrutinized to determine demographics; cause of ESRD; comorbid conditions; method and duration of dialysis; serum calcium, phosphorus, and parathyroid hormone (PTH) levels; peripheral vascular symptoms; and physical findings. All available radiographic studies and noninvasive vascular tests were reviewed. Therapeutic interventions and outcome were carefully documented.
Results The mean age of the five study patients (two men, three women) was 38±14 yr. All patients were on hemodialysis for a mean of 3.7±3 yr. ESRD was attributed to diabetes and hypertension in two, to systemic lupus erythematosis (SLE) in two, and to hypertension in one. One patient had a history of chronic atrial fibrillation, and one had a history of deep venous thrombosis. A summary of patient characteristics is shown in Table 2. The five patients presented to the hospital with tissue loss involving the distal legs and feet. Three patients had nonhealing ulcers, and two had dry gangrene at initial presentation. Tissue loss was bilateral in all patients. Ulcers appeared to be arterial in origin and were located on the anterior ankles and on the dorsal foot surfaces. Gangrene involved the distal third of the forefeet in two patients (Figure 1). Severe skin mottling accompanied the tissue loss in all five patients (livedo reticularis). All five patients had progression of their ischemic lesions in the hospital. At the time of vascular surgery consultation, four of the five had already progressed to wet gangrene, and two had clinical signs of sepsis. Palpable pulses or normal (triphasic) Doppler signals were obtained in the pedal arteries of all five patients (Table 2). None of the patients had upper extremity involvement. The mean calcium–phosphorus product (Ca–PO4, normal range <70) among the five patients was 77±52 (range, 12–143), and three had Ca–PO4 >60. Table 1
Characteristic features of calciphylaxis
Physical exam Distal acral gangrene Palpable distal pulses X-ray Vascular calcifications Laboratory studies Hyperparathyroidism (elevated PTHa) Calcium–phosphorus product >60 Skin punch biopsy Epidermal necrosis Dermal inflammatory infiltrates Medial calcifications a
PTH=parathyroid hormone level
566
The mean PTH level was 629±536 pg/ml (normal 120–240), and four of the five had levels above the normal range. Foot radiographs were available for four of the five patients, all of which demonstrated extensive vascular calcifications involving the distal tibial and pedal arterial segments (Figure 2). All five patients underwent diagnostic punch biopsies of the affected skin, which demonstrated epidermal necrosis, dermal inflammatory infiltrates, and medial calcifications characteristic of calciphylaxis (Figure 3). Aggressive wound care was instituted immediately in all five patients. This included multiple incisions and debridements followed by hydrotherapy and application of skin grafts when feasible. All five patients underwent at least two surgical debridements, and two patients had five operations. The four patients with wet gangrene had rapid progression of tissue loss despite aggressive wound care and expired due to complications of sepsis. The fifth patient had dry gangrene on initial presentation. Amputation below the knee was recommended, but the patient refused. Urgent, bilateral above-knee amputations were eventually performed after the patient developed sepsis, but she ultimately succumbed to diffuse coagulopathy with hemorrhagic shock three weeks later. Subtotal parathyroidectomy was performed in three of the five patients to improve the potential for wound healing and survival as suggested by others [5]. Two patients did not have parathyroidectomy because of sepsis. Parathyroidectomy was performed in the other three at variable intervals during hospitalization when foot infections appeared to be under control. Parathyroidectomy did not delay amputation in any case. However, all three patients had progression of wet gangrene despite parathyroidectomy, and all three died of septic complications.
Discussion Calciphylaxis occurs most commonly in patients with ESRD and secondary hyperparathyroidism. Fortunately, calciphylaxis is rare, affecting less than 1% of patients with both disorders. The exact mechanism of tissue loss in patients with calciphylaxis remains unknown. The underlying pathophysiology has been attributed to widespread deposition of calcium in small arteries of the lower extremity, leading to progressive luminal encroachment and ischemia. While medial calcification seen in skin biopsy specimens provides some evidence that primary calcium deposition may be the initiating step in the development of calciphylaxis, the universal presence of dermal inflammatory infiltration suggest that there may be an additional inflammatory component. One of our five patients with biopsy-proved calciphylaxis did not have an elevated PTH level. At necropsy, this CARDIOVASCULAR SURGERY
DECEMBER 2001 VOL 9 NO 6
CARDIOVASCULAR SURGERY
F
M
M
F F
23
DECEMBER 2001 VOL 9 NO 6
49
55
26 38
ESRD, HTN, SLE ESRD, HTN, IDDM
ESRD, HTN, atrial fib
ESRD, SLE, HTN seizures ESRD, HTN, NIDDM
D/P
Wet gangrene BLE Wet gangrene BLE
Wet gangrene BLE
Wet gangrene BLE
D D
D
P
Dry gangrene both feet P
Physical exam
92 12
39
80–100
143
556 40
847
280
1420
Diagnostics PTH CaXPO4
Patient care
X-ray and Punch biopsy Wound care, amputation, parathryoidectomy X-ray and Punch biopsy Wound care, debridement, parathyroidectomy X-ray and Punch biopsy Wound care, debridement, parathyroidectomy Punch biopsy Local wound care X-ray and post mortem Local wound care exam
X-ray or biopsy
Sepsis, death Sepsis, death
Sepsis, death
Sepsis, death
Coagulopathy, sepsis, death
Outcome
a ESRD: end stage renal disease; SLE: systemic lupus erythematosus; HTN: hypertension; NIDDM: noninsulin dependent diabetes mellitus; BLE: bilateral lower extremities; IDDM: insulin dependent diabetes mellitus; CHF: congestive heart failure; DVT: deep vein thrombosis; P: palpable pedal pulse; D: Doppler signal only
B W
B
B
B
Past medical history
Sex
Age
Race
Summary of patient characteristicsa
Table 2
Wet gangrene in hemodialysis patients: C. A. Davis and R. J. Valentine
567
Wet gangrene in hemodialysis patients: C. A. Davis and R. J. Valentine
Figure 1 Distal forefoot gangrene in a patient with calciphylaxis
Figure 2 Foot radiograph demonstrating extensive calcification of the posterior tibial and plantar arteries
patient proved to have widespread tissue calcification involving multiple organs. This suggests that other mechanisms besides secondary hyperparathyroidism may be responsible for calcium deposition. Accordingly, the incidence of calciphylaxis may be higher than previously suspected in groups of patients with ESRD. 568
The distribution of cutaneous necrosis is highly variable. In addition to acral lesions, previous reports have documented involvement of the proximal leg, fingers, abdominal wall, and penis [5–7]. It appears that the distal feet and toes represent the most common site of involvement, but a number of patients with involvement in other areas may have been diagCARDIOVASCULAR SURGERY
DECEMBER 2001 VOL 9 NO 6
Wet gangrene in hemodialysis patients: C. A. Davis and R. J. Valentine
Figure 3 Punch biopsy of an acral ulcer in a patient with calciphylaxis showing typical medial calcification
nosed incorrectly. Our experience had centered on acral gangrene. None of the patients in the present series had involvement of the thigh, abdominal wall, or upper extremity, so we are unable to comment on the proper management of these lesions. Others have shown that aggressive wound care and digital amputations, combined with timely parathyroidectomy, may lead to significant improvement in many cases [5–9]. Parathyroidectomy has been suggested as the single most important intervention in the long-term treatment of patients with calciphylaxis [5–9]. However, parathyroidectomy had little impact on the outcome of our small group of patients. We suspect that the difference in outcome between patients in our study and the previous reports is associated with the advanced degree of tissue loss in our patients. In the present study, the majority of patients had already progressed to wet gangrene with impending sepsis at the time of surgical consultation. Despite aggressive wound care, these patients progressed rapidly to overwhelming infection and death. Based on the experience of others, we speculate that our patients did not receive parathyroidectomy early enough to reverse changes associated with calciphylaxis. Our small experience suggests that parathyroidectomy does not improve the survival or wound healing potential of patients with calciphylaxis who have already progressed to wet gangrene. We believe that we missed the opportunity to salCARDIOVASCULAR SURGERY
DECEMBER 2001 VOL 9 NO 6
vage the five patients in this study with timely amputations. All five patients in this series were admitted to general medical services with consultations requested from physical medicine, general surgery and vascular services. We feel that the delay in definitive care of these patients was probably due to delay in consulting surgical services. All five patients had developed advanced tissue loss by the time of surgical consultation, and all five expired due to complications of uncontrolled sepsis, despite multiple surgical debridements and aggressive wound care. This suggests that control of sepsis is paramount in patients with advanced complications of calciphylaxis. The decision for amputation is clearly based on individual circumstances, but our experience suggests that local wound care is not adequate therapy in advanced cases of tissue loss due to calciphylaxis. While it would have been desirable to treat the wounds in the early stages, before ischemia progressed to wet gangrene, we were not afforded this opportunity. In fact, parathyroidectomy may have had significant benefit in healing open wounds in the earlier stages. Accordingly, we advocate early referral of these patients to the surgeon to ensure timely wound care and prevention of infection. We consider the onset of advanced gangrene, particularly if associated with infection, as an indication for primary amputation. We acknowledge that there are significant limitations with this study. Because it is retrospective in 569
Wet gangrene in hemodialysis patients: C. A. Davis and R. J. Valentine
nature, a number of patients with calciphylaxis who had a more favorable outcome may have been missed. Specifically, some patients with minimal tissue loss may not have been seen by the surgery service. It is unlikely that any patient with infectious complications requiring operative debridement would have been missed, although some requiring minimal debridement at the bedside may have gone undetected. However, including additional patients with less advanced ischemia would not have altered our conclusions that outcome is largely affected by the onset of superimposed sepsis. Patients with less extensive tissue loss may benefit from parathyroidectomy, but our data suggest that patients with wet gangrene tend to suffer early deaths, before any long term benefit can be achieved. In summary, our experience with five patients who had advanced forefoot ischemia due to calciphylaxis suggests that early outcome is predicated on the degree of tissue loss. Aggressive wound care does not appear to be adequate to control infection in patients who have already developed gangrene. Our limited experience suggests that major amputations are indicated in these circumstances. Although parathyroidectomy may have important long-term advantages, it does not appear to affect outcome in these advanced cases.
570
References 1. Johnson, B. L., Glickman, M. D., Bandyk, D. F. et al., Failure of foot salvage in patients with end-stage renal disease after surgical revascularization. Journal of Vascular Surgery, 1995, 22, 280–286. 2. Androgue, J. H., Frazier, M. R., Zeloff, B. et al., Systemic calcinosis revisited. American Journal of Nephrology, 1981, 1, 175– 183. 3. Angelis, M., Wong, L. L., Myers, S. et al., Calciphylaxis in patients on hemodialysis: a prevalence study. Surgery, 1997, 122, 1083–1090. 4. Dereure, O., Leray, H., Barneon, G. et al., Extensive necrotizing livedo reticularis in a patient with chronic renal failure, hyperparathyroidism, and coagulation disorder: regression after subtotal parathyroidectomy. Dermatology, 1996, 192, 167–170. 5. Duh, Q. Y., Lim, R. C. and Clark, O. H., Calciphylaxis in secondary hyperparathyroidism. Archives of Surgery, 1991, 7, 1213–1218. 6. Coates, T., Kirkland, G. S., Dymock, R. B. et al., Cutaneous necrosis from calcific uremic arteriopathy. American Journal of Kidney Disease, 1998, 32, 384–391. 7. Bleyer, A. J., Choi, M., Igwemezie, B. et al., A case control study of proximal calciphylaxis. American Journal of Kidney Disease, 1998, 32, 376–383. 8. Hafner, J., Keusch, G., Wahl, C. et al., Uremic small-artery disease with medial calcification and intimal hyperplasia (so-called calciphylaxis): a complication of chronic renal failue and benefit from parathyroidectomy. Journal of the American Academy of Dermatology, 1995, 33, 954–962. 9. Skinner, K. A. and Zuckerbraun, L., Recurrent secondary hyperparathyroidism (an argument for total parathyroidectomy). Archives of Surgery, 1996, 131, 724–727. Paper accepted 1 May 2001
CARDIOVASCULAR SURGERY
DECEMBER 2001 VOL 9 NO 6