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Two cases of purpura fulminans
TWO C A S E S OF P U R P U R A F U L M I N A N S
By EDITH FREDERIKS,MoD. University Hospital, Leiden and A. J. C. HUFFSTADT,M.D. University Hospital, Groningen, The Netherlands FOR the diagnosis of purpura fulminans, Hjort et aL (I964) laid down the following criteria : it is a disease of children, preceded by a benign infection after a latent period characterised by skin hmmorrhages with rapid progression in waves and severe afibrinogenmmia ; if the patient survives this critical phase, extensive skin necrosis follows ; blood-coagulation abnormalities are found due to intravascular thrombosis as can be demonstrated by skin biopsy. Differential Diagnosis.mWith these criteria purpura fulminans is a different entity from other kinds of purpura following infectious diseases ; the latter are mostly more superficially situated in the skin and are usually due to increased permeability of small vessels ; thrombocytopenia and disturbances in blood-coagulations are seldom found. With purpura fulminans, afibrinogenmmia and thrombocytopenia are an essential feature while factors II, v and VIII are diminished. The whole process might be thus explained : following the infectious disease, antigen-antibody complexes settle in the reticulo-endothelial system causing thrombocyte disintegration which results in thrombosis in the small vessels. For this thrombosing process the various coagulation factors are used up and this leads to hmmorrhage. Skin biopsy in these cases has shown intravascular thrombosis in the small vessels. C a u s e . ~ T h e question as to which comes first : thrombosis or hmmorrhage in the skin, or whether both occur simultaneously, is still unsolved, but therapeutic successes with heparin have indicated that thrombosis is most likely to be the primary lesion, caused by an as yet unknown agent. I f heparin is given in sufficiently high dosage to prevent any blood-coagulation (I5O i.u. per kg. body weight every 4 to 6 hours i.v. during at least one week) curiously enough no more extensions of the hmmorrhages are found and hmmostatic factors return in the blood. In 1964 out of more than ioo cases described since 1884 (Guelliot, I884 ; Henoch, 1887) as purpura fulminans, Hjort selected 5o to which his above-mentioned criteria applied. The onset of the disease after a latent period following the recovery of a seemingly benign infection, indicates that the cause may be sought in a hypersensitive reaction as in Shwartzman's phenomenon. The real cause is still unknown. T r e a t m e n t . - - F o r the above-mentioned reasons, treatment cannot be essentially specific. The following measures however have been found beneficial : Heparin, for reasons explained above (Little, I959 ; van Dam et al., I965 ; Allen, 1966 ; Antley and McMillan, I967). Blood transfusion to combat shock and anmmia, deficiencies in fibrinogen and other blood-coagulation factors. Corticosteroids (van Creveld et al., I965), not to diminish the production of antibodies but rather to stop symptoms secondary to antigen-antibody reaction. It might be thought dangerous to use corticosteroids as these depress the RES and so may increase abnormalities in the blood, but with heparin admLnistration this need not be feared. High doses of penicillin to exclude the production of bacterial antigens. 9o
TWO CASES OF PURPURA F U L M I N A N S
9I
Apart from these measures others have been proposed : Dextran, which acts as an anti-thrombotic agent besides combating hypovohemia (Moncrief et al., 1963 ; Patterson et al., 1965 ; Gruber and Bergentz, 1966). Epsilon-aminocaproic acid, which would seem contra-indicated since by preventing solution ofthrombi it will promote thrombosis. Mention must be made however, of two cases in which from the moment of administration of eaca, progression of the purpura seemed halted. Hyperbaric oxygen has only been described as useful in a case which did not fulfil the criteria for the diagnosis of purpura fulminans, but it may be helpful as an addition to the treatments mentioned above (Waddell et aL, 1965). CASE REPORTS Case I.--A 2-year-old girl became seriously ill 13 days after an attack of staphylococcal angina ; cutaneous and subcutaneous hmmorrhagic infarctions appeared first on right lower leg and knee, on the left thigh and hip, and spread during the next six days over both legs leaving only the medial side of the right thigh free. Four days later, small infarctions were noted on the left cheek and right shoulder and upper arm which healed without intervention. During this illness blood-coagulation was completely disturbed and afibrinogenmmia diagnosed. Treatment at that time (1961) consisted of fresh blood and fibrinogen transfusions, prednisolone and antibiotics. After the patient had survived the critical phase, the left extremity had lost vitality from halfway down the lower leg with deep necrosis reaching laterally upwards to the left flank. To prevent a future prosthesis pressing on transplanted skin in the hip area, a subtrochanteric amputation was performed using the local skin flaps to cover the stump. On the right leg the necrosed skin was removed and the area temporarily covered with anmion, followed by skin transplantation during the following weeks (donor areas : abdomen and medial side of the right thigh). The child learned to walk well with the prosthesis but being careless with the grafted skin on her right kneecap, had recurrent small ulceration in that area (Figs. 1-3). Case ~.--A 6-year-old girl having recovered from an illness resembling scarlet fever three weeks before, became likewise seriously ill with hmmorrhagic infarctions spreading very rapidly over both legs with afibrinogememia. Medical treatment was the same as with the 2-year-old girl. After the critical phase, the necrotic tissue on the right leg was excised, the left leg amputated above the knee and the raw areas skin grafted (donor areas : right arm and abdomen) (Figs. 4 and 5). DISCUSSION Since 1961 when the two cases reported occurred, more is known about the histopathological changes in skin and small vessels in such cases ; intravascular thrombosis has been found in capillaries and venules. The question whether thrombosis or hmmorrhage is the starting point in the skin lesions, or even if both occur simultaneously, is still unsolved but therapeutic successes have indicated that thrombosis is most likely to be the primary lesion caused by an as yet unknown agent. As the disturbances in hmmostasis accompanied by afibrinogenmmia, thrombocytopenia and deficiency of factors II, V and VIII have been successfully treated by heparin they are thought to be caused by this thrombosis. Heparin is now considered the best form of treatment and is administered in a dosage of 15o i.u. per kg. body weight every 4 to 6 hours i.v. for at least one week. Transfusions of fresh whole blood and fibrinogen are usually necessary to combat shock, anmmia and afibrinogenmmia. Corticosteroids may be administered against
92
B R I T I S H J O U R N A L OF P L A S T I C SURGERY
Case r.
Case r.
FIG. z Six days later.
FIG. I O n admission.
,
Case I.
Fig. 3F i v e years after amputation.
antigen-antibody reactions, and penicillin against the bacterial antigens which may have played a role in the onset of the disease but it must be realised that none of these measures can boast of being specific.
TWO CASES OF PURPURA F U L M I N A N S
Case 2.
Case 2.
Fro. 4 N e c r o s e d areas,
FIG. 5 Five years after a m p u t a t i o n .
93
94
BRITISH JOURNAL OF PLASTIC SURGERY
About half of all cases of purpura fulminans survive the critical phase and need surgical treatment for extensive tissue necrosis. Two problems as yet unsolved arise here : Can amputations be prevented by early incisions in the necrosing skin areas thereby preventing deep necrosis due to circumferential constriction? Or are these necroses so deep primarily that no such measures can be of any use? In the amputated leg of the 2-year-old girl only the main vessels were open to halfway down the calf which does not prove anything as it is known that thrombosis in this disease starts in the small vessels and may have progressed to the next larger whilst constriction may or may not have played a role at the same time. How early shouM surgical excision be started? Could it be done as soon as superficial progression in the skin has stopped and heparin treatment has been finished, according to the literature, usually after at least eight days? Might such early excisions prevent further extension in deeper layers ? It seems that only experience will be able to tell, and therefore we would like to urge colleagues all over the world to publish their cases.
The question of scarcity of donor areas for skin transplantation in these patients may now be solved by the use of mesh-grafts, although in children we would, where possible, prefer larger grafts. Levels of amputation must be chosen according to the situation in each individual case bearing in mind that less valid skin coverage gives rise to more problems in children who do not heed weak areas and need a succession of prostheses during their development. As p,'ediatricians and haemostasis specialists usually start the treatment of these patients, they should be emphatically advised on the role of the surgeon who should be invited to join the team immediately to safeguard against the dangers of circumferential skin necrosis and to decide the earliest possible moment for excision of necrotic skin areas and skin grafting. Consultation with orthopaedic surgeons, prostheticians and rehabilitation specialists regarding the decision on the level of amputation in each case is considered desirable. SUMMARY
I. Two cases of purpura fulminans which fulfilled the diagnostic criteria of Hjort (1964) are described. 2. Both cases had widespread necrosis of the legs requiring amputation and skin grafting. 3- The aetiology and treatment are discussed. Figures I-5 are reproduced by courtesy of" Nederlands Tijdschrift voor Geneeskunde ". REFERENCES ALLEN, D. M. (1966). Pediatrics, 38, 211. ANTLEY,R. M. and McMILLAN, C. W. (1967). New Engl. J. Med. 276, 1287. CREVELD, S. VAN, KOLK, W. F. J. VAN DER, MOCHTAR,I. A. and MULLER,J. (I965). Clin. Pedlar. 4, 23. DAM, J. VAN,HENSEN,A., LOELIGER,E. A. and LEEKSMA,C. H. W. (1965). Ned. Tijdschr. Geneesk. lO9, 894. GRImEX,U. F. and BERGEI~rrz,S. E. (1966). .~. surg. Res. 6, 379GLmLLIOT,O. (1884). Un. todd. sciem. NE. 8, 25. HENoCI-I,E. (1887). Berl. klin. Wschr, 24, 8. HJORT, P. F., RAPAPORT,S. i. and J~RGENSEN,L. (1964). Scand. J. Hcemat, 1, 169. LITTLE,J. R. (1959). J. Am. med. Ass. 169, 36. MONCa~IEF,J. A., DARIN,J. C., CAmZARO,P. C. and SAWYER,R. I3. (1963). Ann. Surg. 158, 553. PATTERSON, J. H., PmRCE, R. B., AME~SON, J. R. et aL (1965). N e w Engl. J. Med. 273, 734. WADDELL, W. B., SALTZMA-~, H. A. FUSON, R. L. and H~.ms, J. (1965)..7. Am. reed.Ass. 191, 971.
By EDITH FREDERIKS,MoD. University Hospital, Leiden and A. J. C. HUFFSTADT,M.D. University Hospital, Groningen, The Netherlands FOR the diagnosis of purpura fulminans, Hjort et aL (I964) laid down the following criteria : it is a disease of children, preceded by a benign infection after a latent period characterised by skin hmmorrhages with rapid progression in waves and severe afibrinogenmmia ; if the patient survives this critical phase, extensive skin necrosis follows ; blood-coagulation abnormalities are found due to intravascular thrombosis as can be demonstrated by skin biopsy. Differential Diagnosis.mWith these criteria purpura fulminans is a different entity from other kinds of purpura following infectious diseases ; the latter are mostly more superficially situated in the skin and are usually due to increased permeability of small vessels ; thrombocytopenia and disturbances in blood-coagulations are seldom found. With purpura fulminans, afibrinogenmmia and thrombocytopenia are an essential feature while factors II, v and VIII are diminished. The whole process might be thus explained : following the infectious disease, antigen-antibody complexes settle in the reticulo-endothelial system causing thrombocyte disintegration which results in thrombosis in the small vessels. For this thrombosing process the various coagulation factors are used up and this leads to hmmorrhage. Skin biopsy in these cases has shown intravascular thrombosis in the small vessels. C a u s e . ~ T h e question as to which comes first : thrombosis or hmmorrhage in the skin, or whether both occur simultaneously, is still unsolved, but therapeutic successes with heparin have indicated that thrombosis is most likely to be the primary lesion, caused by an as yet unknown agent. I f heparin is given in sufficiently high dosage to prevent any blood-coagulation (I5O i.u. per kg. body weight every 4 to 6 hours i.v. during at least one week) curiously enough no more extensions of the hmmorrhages are found and hmmostatic factors return in the blood. In 1964 out of more than ioo cases described since 1884 (Guelliot, I884 ; Henoch, 1887) as purpura fulminans, Hjort selected 5o to which his above-mentioned criteria applied. The onset of the disease after a latent period following the recovery of a seemingly benign infection, indicates that the cause may be sought in a hypersensitive reaction as in Shwartzman's phenomenon. The real cause is still unknown. T r e a t m e n t . - - F o r the above-mentioned reasons, treatment cannot be essentially specific. The following measures however have been found beneficial : Heparin, for reasons explained above (Little, I959 ; van Dam et al., I965 ; Allen, 1966 ; Antley and McMillan, I967). Blood transfusion to combat shock and anmmia, deficiencies in fibrinogen and other blood-coagulation factors. Corticosteroids (van Creveld et al., I965), not to diminish the production of antibodies but rather to stop symptoms secondary to antigen-antibody reaction. It might be thought dangerous to use corticosteroids as these depress the RES and so may increase abnormalities in the blood, but with heparin admLnistration this need not be feared. High doses of penicillin to exclude the production of bacterial antigens. 9o
TWO CASES OF PURPURA F U L M I N A N S
9I
Apart from these measures others have been proposed : Dextran, which acts as an anti-thrombotic agent besides combating hypovohemia (Moncrief et al., 1963 ; Patterson et al., 1965 ; Gruber and Bergentz, 1966). Epsilon-aminocaproic acid, which would seem contra-indicated since by preventing solution ofthrombi it will promote thrombosis. Mention must be made however, of two cases in which from the moment of administration of eaca, progression of the purpura seemed halted. Hyperbaric oxygen has only been described as useful in a case which did not fulfil the criteria for the diagnosis of purpura fulminans, but it may be helpful as an addition to the treatments mentioned above (Waddell et aL, 1965). CASE REPORTS Case I.--A 2-year-old girl became seriously ill 13 days after an attack of staphylococcal angina ; cutaneous and subcutaneous hmmorrhagic infarctions appeared first on right lower leg and knee, on the left thigh and hip, and spread during the next six days over both legs leaving only the medial side of the right thigh free. Four days later, small infarctions were noted on the left cheek and right shoulder and upper arm which healed without intervention. During this illness blood-coagulation was completely disturbed and afibrinogenmmia diagnosed. Treatment at that time (1961) consisted of fresh blood and fibrinogen transfusions, prednisolone and antibiotics. After the patient had survived the critical phase, the left extremity had lost vitality from halfway down the lower leg with deep necrosis reaching laterally upwards to the left flank. To prevent a future prosthesis pressing on transplanted skin in the hip area, a subtrochanteric amputation was performed using the local skin flaps to cover the stump. On the right leg the necrosed skin was removed and the area temporarily covered with anmion, followed by skin transplantation during the following weeks (donor areas : abdomen and medial side of the right thigh). The child learned to walk well with the prosthesis but being careless with the grafted skin on her right kneecap, had recurrent small ulceration in that area (Figs. 1-3). Case ~.--A 6-year-old girl having recovered from an illness resembling scarlet fever three weeks before, became likewise seriously ill with hmmorrhagic infarctions spreading very rapidly over both legs with afibrinogememia. Medical treatment was the same as with the 2-year-old girl. After the critical phase, the necrotic tissue on the right leg was excised, the left leg amputated above the knee and the raw areas skin grafted (donor areas : right arm and abdomen) (Figs. 4 and 5). DISCUSSION Since 1961 when the two cases reported occurred, more is known about the histopathological changes in skin and small vessels in such cases ; intravascular thrombosis has been found in capillaries and venules. The question whether thrombosis or hmmorrhage is the starting point in the skin lesions, or even if both occur simultaneously, is still unsolved but therapeutic successes have indicated that thrombosis is most likely to be the primary lesion caused by an as yet unknown agent. As the disturbances in hmmostasis accompanied by afibrinogenmmia, thrombocytopenia and deficiency of factors II, V and VIII have been successfully treated by heparin they are thought to be caused by this thrombosis. Heparin is now considered the best form of treatment and is administered in a dosage of 15o i.u. per kg. body weight every 4 to 6 hours i.v. for at least one week. Transfusions of fresh whole blood and fibrinogen are usually necessary to combat shock, anmmia and afibrinogenmmia. Corticosteroids may be administered against
92
B R I T I S H J O U R N A L OF P L A S T I C SURGERY
Case r.
Case r.
FIG. z Six days later.
FIG. I O n admission.
,
Case I.
Fig. 3F i v e years after amputation.
antigen-antibody reactions, and penicillin against the bacterial antigens which may have played a role in the onset of the disease but it must be realised that none of these measures can boast of being specific.
TWO CASES OF PURPURA F U L M I N A N S
Case 2.
Case 2.
Fro. 4 N e c r o s e d areas,
FIG. 5 Five years after a m p u t a t i o n .
93
94
BRITISH JOURNAL OF PLASTIC SURGERY
About half of all cases of purpura fulminans survive the critical phase and need surgical treatment for extensive tissue necrosis. Two problems as yet unsolved arise here : Can amputations be prevented by early incisions in the necrosing skin areas thereby preventing deep necrosis due to circumferential constriction? Or are these necroses so deep primarily that no such measures can be of any use? In the amputated leg of the 2-year-old girl only the main vessels were open to halfway down the calf which does not prove anything as it is known that thrombosis in this disease starts in the small vessels and may have progressed to the next larger whilst constriction may or may not have played a role at the same time. How early shouM surgical excision be started? Could it be done as soon as superficial progression in the skin has stopped and heparin treatment has been finished, according to the literature, usually after at least eight days? Might such early excisions prevent further extension in deeper layers ? It seems that only experience will be able to tell, and therefore we would like to urge colleagues all over the world to publish their cases.
The question of scarcity of donor areas for skin transplantation in these patients may now be solved by the use of mesh-grafts, although in children we would, where possible, prefer larger grafts. Levels of amputation must be chosen according to the situation in each individual case bearing in mind that less valid skin coverage gives rise to more problems in children who do not heed weak areas and need a succession of prostheses during their development. As p,'ediatricians and haemostasis specialists usually start the treatment of these patients, they should be emphatically advised on the role of the surgeon who should be invited to join the team immediately to safeguard against the dangers of circumferential skin necrosis and to decide the earliest possible moment for excision of necrotic skin areas and skin grafting. Consultation with orthopaedic surgeons, prostheticians and rehabilitation specialists regarding the decision on the level of amputation in each case is considered desirable. SUMMARY
I. Two cases of purpura fulminans which fulfilled the diagnostic criteria of Hjort (1964) are described. 2. Both cases had widespread necrosis of the legs requiring amputation and skin grafting. 3- The aetiology and treatment are discussed. Figures I-5 are reproduced by courtesy of" Nederlands Tijdschrift voor Geneeskunde ". REFERENCES ALLEN, D. M. (1966). Pediatrics, 38, 211. ANTLEY,R. M. and McMILLAN, C. W. (1967). New Engl. J. Med. 276, 1287. CREVELD, S. VAN, KOLK, W. F. J. VAN DER, MOCHTAR,I. A. and MULLER,J. (I965). Clin. Pedlar. 4, 23. DAM, J. VAN,HENSEN,A., LOELIGER,E. A. and LEEKSMA,C. H. W. (1965). Ned. Tijdschr. Geneesk. lO9, 894. GRImEX,U. F. and BERGEI~rrz,S. E. (1966). .~. surg. Res. 6, 379GLmLLIOT,O. (1884). Un. todd. sciem. NE. 8, 25. HENoCI-I,E. (1887). Berl. klin. Wschr, 24, 8. HJORT, P. F., RAPAPORT,S. i. and J~RGENSEN,L. (1964). Scand. J. Hcemat, 1, 169. LITTLE,J. R. (1959). J. Am. med. Ass. 169, 36. MONCa~IEF,J. A., DARIN,J. C., CAmZARO,P. C. and SAWYER,R. I3. (1963). Ann. Surg. 158, 553. PATTERSON, J. H., PmRCE, R. B., AME~SON, J. R. et aL (1965). N e w Engl. J. Med. 273, 734. WADDELL, W. B., SALTZMA-~, H. A. FUSON, R. L. and H~.ms, J. (1965)..7. Am. reed.Ass. 191, 971.