|Year : 2014 | Volume
| Issue : 2 | Page : 98-102
Symmetrical peripheral gangrene and extremity amputations
Friday S Ejagwulu1, Abdulrasheed Ibrahim2
1 Department of Orthopaedics and Trauma Surgery, Division of Plastic Surgery, Ahmadu Bello University Teaching Hospital, Shika-Zaria, Kaduna State, Nigeria
2 Department of Surgery, Division of Plastic Surgery, Ahmadu Bello University Teaching Hospital, Shika-Zaria, Kaduna State, Nigeria
|Date of Web Publication||16-Mar-2015|
Department of Surgery, Division of Plastic Surgery, Ahmadu Bello University Teaching Hospital, P.M.B. 06, Shika Zaria, Kaduna
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Symmetrical peripheral gangrene (SPG) is a rare syndrome. It is characterized by bilateral distal ischemia leading to gangrene, in the absence of major vascular occlusive disease. It is considered a cutaneous marker of disseminated intravascular coagulation, and more than half of the patients who survive require amputation of the affected limb(s). The etio-pathogenesis of SPG is not well understood, but the hallmark is the occurrence of microcirculatory failure. We present two patients with SPG. The aim of this report is to sensitize and to help make the diagnosis easier for the clinician. Patients who are identified to be at risk require frequent observation and examination of the appearance of their distal extremities, nose, and ears. No treatment is universally effective. It should be individualized according to the underlying disease and patient's general condition. The guiding principle is prompt identification and reduction or removal of aggravating factors.
Keywords: Amputations, distal extremities, gangrene, sepsis, symmetrical
|How to cite this article:|
Ejagwulu FS, Ibrahim A. Symmetrical peripheral gangrene and extremity amputations. Ann Nigerian Med 2014;8:98-102
| Introduction|| |
Amputations are usually the result of complications of diabetes mellitus, peripheral arterial disease, trauma, and malignant tumors. Infections contribute significantly to the incidence of amputations, however, infections are typically preceded by the above conditions.  There are occasional reports in medical literature of symmetrical peripheral gangrene (SPG) and subsequent extremity amputation following systemic infection. 
Symmetrical peripheral gangrene was first described by Hutchison in 1891 in a 37-year-old male who developed gangrene of fingers, toes, and ear lobules after shock. , It is characterized by bilateral distal ischemia leading to gangrene, in the absence of major vascular occlusive disease. , It is a devastating syndrome and mortality is estimated to be up to 40%. More than half of the patients who survive require amputation of the affected limb. ,
Symmetrical peripheral gangrene is a rare syndrome. A recent literature search revealed less than 100 cases. This accounts for the lack of consistent information regarding its incidence, etiology, prevention, and management. ,, The loss of an extremity may manifest as an extensive and evolving threat to the physical, psychological, and social functioning of the patient. , The purpose of this report is to present a recent experience with this syndrome, and to discuss potential risk factors and management of SPG. This additional information will help in the prevention of gangrene, reducing the socioeconomic problems arising from amputation.
| Case Report|| |
A 5-year-old male child presented with symmetrical auto-amputation at the distal third of both legs and amputation stumps of the second, third and fourth digit of both hands [Figure 1]. There was a history of fever associated with chills and rigors, headache, and malaise 3 weeks prior to presentation. The mother subsequently noticed a gradually progressive peripheral darkening of the distal third of the digits of both hands and the feet, which started on day 6 of the fever. He also developed jaundice, decreased urine output and altered sensorium during the course of his illness. The parents sought unorthodox treatment with herbal medications (applications of pastes and oral herbs). There was no past history of trauma or thrombo-embolic episodes.
|Figure 1: (a) Auto-amputation at the distal third of both legs and (b) distal interphalangeal joints of the second, third and fourth digits of both hands|
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General physical examination revealed an anxious boy. He was pale, febrile and dehydrated. He had septic amputation stumps at the distal third of the tibia and fibula and healed symmetrical stumps of the index, middle and ring fingers of both hands. The skin around the digits was warm to touch with normal sensations to touch, pain, and temperature. All the peripheral pulses of the affected limbs were normal. Cardiovascular and respiratory examinations were unremarkable. A peripheral blood film showed trophozoites of Plasmodium falciparum. The hemoglobin was 9 g/dl, with a neutrophil count of 61% and the total white blood cell count was elevated (15,000/ml 3 ). The peripheral smear showed anisopoikilocytosis with polychromasia. The blood culture was sterile. Due to financial constraints and the absence of clinical manifestations, the investigations for a hyper-coagulable state was not done. A diagnosis of complicated P. falciparum malaria with disseminated intravascular coagulation (DIC) resulting in SPG was made. He was resuscitated with intravenous fluid and had blood transfusion with packed cells. He had treatment with anti-malarial (artemether-lumefantrine) and broad spectrum antibiotics. He had a refashioning of the amputation of the tibia and fibula, and was discharged for follow-up at the orthopedic outpatient department. Patient is however yet to procure his prosthesis.
A 48-year-old lady had a complaint of fever associated with chills and rigors for 3 weeks. She was seen at a peripheral clinic and had a prescription of drugs, which patient could not give the details. She subsequently noticed darkening of right half of the upper lip and all the digits of the both hands and feet, which was painful and progressive over a 1 week period. There was no history of cough, abdominal pain or vomiting. There were no genitourinary symptoms. On physical examination, she was afebrile, dehydrated, and pale. There was no significant peripheral lymphadenopathy. A pulse rate of 125/min, respiratory rate of 28/min, and blood pressure of 100/70 mmHg was recorded. The radial, femoral and popliteal pulses were all palpable. Examination of both upper and lower limbs revealed blackish discoloration of all digits of both hands up to the metacarpophalangeal joints, and all the toes extending up to middle third of the leg [Figure 2].
The overlying skin was cold and dry with definite lines of demarcation between the gangrenous and normal skin. Investigations revealed a haemoglobin of 9.8 g/dl, and a total leukocyte count of 15,600/mm 3 . Peripheral blood smear revealed a normocytic hypochromic picture with neutrophilia and left shift. Blood biochemistry revealed normal parameters. Urine and blood cultures were sterile. A clinical diagnosis of SPG was considered. Initially, she underwent bilateral amputation below the knee joint. Two weeks after the first operation, bilateral digital amputations were carried out at the level of the metacarpophalangeal joints. Wound healing was uneventful and she was discharged from hospital 3 weeks later. She was given a referral for prosthesis of the lower limbs, but she is unable to afford it because of lack of funds.
| Discussion|| |
The etio-pathogenesis of SPG is not well understood, but the hallmark is the occurrence of microcirculatory failure.  It is thus reasonable to speculate that for SPG to become established there must be a low-flow state in the microcirculation of the affected parts, leading to occlusion of these vessels.  DIC has been suggested as crucial in the pathogenesis of vascular occlusion. It has been described in several reports as the cutaneous marker of DIC. ,,,
Gram-negative septicemia is most commonly associated with clinically overt DIC occurring in 30-50% of patients, and contrary to the common belief, it appears to be equally common in Gram-positive sepsis.  Microbial endotoxins (lipopolysaccharide) and exotoxins induce generalized inflammatory response that is characterized by activation of cytokines. The ensuing septicemic shock may lead to occlusion of the reticulo-endothelial system and prevent the rapid clearing of platelet and fibrin microemboli. 
Symmetrical peripheral gangrene has also been reported in falciparum malaria.  Again, the exact mechanism, which may initiate intravascular coagulation in malaria remains unclear. However, significant parasitemia may activate the complement system, trigger the coagulation pathway, and lead to an alteration in lipid distribution across the parasitized erythrocytes, with an activation of the intrinsic coagulation pathway. The parasitized erythrocytes remain in the microcirculation by a molecular interaction with endothelial receptors, mainly vascular cell adhesion molecule I, intercellular adhesion molecule I, and histidine-rich protein.  The sequestration of parasitized erythrocytes due to the decreased deformability of red cells and/or adherence of infected red cells to microvascular endothelium is thought to initiate microcirculatory occlusion in malaria.  Elevated levels of fibrin/fibrinogen degradation products reflecting the ongoing fibrinolysis have been documented, even in uncomplicated falciparum malaria.  SPG can also occur as a complication of ergotism, measles, protein C or S or antithrombin III deficiency, and malignancy. It is aggravated by increased sympathetic tone, cold injury to extremities, use of vasopressors, diabetes mellitus and renal failure. ,
Laboratory markers consistent with the diagnosis of DIC include prolongation of prothrombin time (increased international normalized ratio value), platelet count of <100,000/mm 3 , and a low fibrinogen concentration.  Tests for fibrin-degradation products or d-dimers may be helpful to differentiate DIC from other conditions that are associated with a low platelet count or prolonged clotting times. 
Intense reflex vasoconstriction in the digital vessels of the extremities may cause a nonthrombotic occlusion when the intraluminal hydrostatic pressure falls below the critical closing pressure.  The onset is typically insidious and dependent upon blood supply; regions of the body with excellent blood supply are relatively protected, while precarious blood supply served by end arteries increases susceptibility.  Frequently affected parts of the body therefore, are the toes, feet, fingers, hands ear lobes and penis. , The ischemic changes in the limbs begin distally and may progress proximally to involve the entire extremity.  Dry gangrene is commonly a result of arterial occlusion associated with limited putrefaction and absence of invasive bacterial proliferation. 
Symmetrical peripheral gangrene can develop at any age and in either sex. , A strong index of suspicion by the physician is instrumental in establishing the diagnosis.  The first sign of vascular compromise maybe fever followed by marked coldness, pallor, cyanosis, pain and restricted mobility of the extremities.  Infrequently, clinical features of the underlying condition may be apparent and help in early recognition of the syndrome. Clinical evidence of DIC such as bleeding from multiple sites, multiple organ failure, and severe acidosis may be present initially or develop subsequently.  Cyanosis and hemorrhagic bullae may develop in a symmetrical acral distribution over the fingers and toes.  These changes are usually associated in the early stages with intact distal pulses.  Symptoms progress and if not reversed, manifests as dry gangrene which becomes apparent within the first 12-24 h after the onset of these changes. ,, This advances proximally with a line of demarcation developing in about 14 days. In severe cases, auto-amputation may occur.  Autopsy often reveals thrombi concentrated in the small vessels and not the large vessels. ,,,
No treatment is universally satisfactory. Rather, treatment should be guided by the underlying disease and the patient's general condition.  The guiding principle is a prompt identification and reduction or elimination of aggravating factors. , Accepted first-line measures include, an early and aggressive intervention with appropriate antibiotics for sepsis and shock, and cautious anticoagulation if there is evidence of DIC. ,, Management of falciparum malaria should be started immediately with the suspicion of falciparum malaria as the etiology of SPG.  Adjuvant therapy with topical nitroglycerine, intravenous epoprostenol, sympathetic blockade, and hyperbaric oxygen have been reported in the management of established SPG, with dismal outcomes. ,,
The findings of this report suggest similarities with the demographic and clinical pattern described in earlier studies. ,,,,, It is seen in all age groups with no particular predilection for gender, with a devastating clinical outcome of symmetrical multiple limb amputations.
Existing data show that DIC was present in up to 85% of patients with SPG.  We considered severe malaria and infection leading to sepsis as the predominant cause of DIC in our patients. DIC is one of the World Health Organization (WHO) criteria for severe malaria, and serve as an independent marker of poor prognosis.  The WHO defines complicated malaria as those accompanied with one or more of the following clinical or laboratory findings, that is, an impaired level of consciousness, severe anemia, hypoglycemia, acidosis, hyperlactatemia, hyperparasitemia of more than 5%, and renal impairment.  In most of the published cases reporting on SPG, parasitemia is either not mentioned or not exceptionally elevated. Our patient had already received a single loading dose of artemether-lumefantrine before the first determination of parasitemia. SPG appears usually within the first 3 days, even with effective anti-malarial therapy, at which time parasitemia is often very significantly reduced. ,
Disseminated intravascular coagulation due to bacterial infections is the major cause of SPG. ,, Consistent with diagnosis of sepsis, our patient had an infection with evidence of systemic inflammatory response syndrome. However, the blood and urine cultures were negative. Nevertheless, in the present case and in most of the cases reported in the literature, fever followed by other constitutional symptoms, cyanosis, pallor, and pain in the affected limbs, is strongly suggestive of SPG. ,
The affected extremities should be protected from further trauma, cold, and secondary infection.  Amputation may be inevitable, but it is rarely urgently required.  The patient should be observed carefully while demarcation of the gangrene occurs, and only then should amputation be done. This preliminary conservative approach helps in avoiding loss of viable tissue and gives ample time for the patient's clinical condition to become stable. , Appropriate debridement and grafting or major amputation can usually be done on a planned basis.  The level of amputation should be determined by the line of demarcation of gangrene and considerations of stump stability, requirements for prosthesis, and ambulation. 
| Conclusion|| |
These cases were reported so as to sensitize, and make the diagnosis of SPG easier for the clinician. Patients who are identified to be at risk require frequent observation and examination of the appearance of their distal extremities, nose, and ears. At the first sign of marked coldness, pallor, cyanosis, or pain in these areas, SPG should be suspected. It is tragic to have patients who survive sepsis or complicated P. falciparum malaria, do so with the loss of hands and/or feet. 
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[Figure 1], [Figure 2]