Immune competence and diabetes mellitus: Pyogenic human hand infections An unexpectedly high incidence of diabetes mellitus was found in 12 patients with pyogenic hand infections. Three patients had overt diabetes, four had latent diabetes, and only five were normal when tested after resolution of the acute injiamatory state. Cellular immunity, assessed in five patients by intradermal injections of common antigens and the topical application of the neoantigen, dinitrochlorobenzene, appeared to be grossly normal in all patients . If changes in immunity were present, it is likely that the skin tests were not sensitive enough to detect these alterations.
Mark A. Mandel, M.D., Cleveland, Ohio
Patients with diabetes mellitus have an increased susceptibility to some infectious agents; an immune basis for this altered response has not been defined as yet. In the present study 12 patients with deep pyogenic hand infections treated during a 4 year interval were evaluated for diabetes mellitus. Cellular immunity was assessed by the intradermal injection of common antigens and the topical application of dinitrochlorobenzene (DNCB). Prior to insulin treatment, infectious diseases, especially those of mycotic origin, were a major cause of death in patients with diabetes.! It long has been suspected that patients with diabetes have an impaired ability to combat infections. Diabetic patients, when ketotic ,2. 3 have been found to have impaired phagocytosis and to have altered white cell chemotactic ability.4 Alteration in the metabolic pathways of patients with diabetes appears to be responsible for leukocyte dysfunction. 5 • 6 Humoral immunity in diabetic animals, on the other hand, does not seem to be impaired. 7 The surface immunoglobulins in both diabetic and normal white cells appear to be similar. 4 Few studies on cellular immunity in patients with diabetes have been published. In 1974, MacCuish and co-workers8 reported the first quantitative evaluation of
From the Department of Surgery, Division of Plastic Surgery, Case Western Reserve University Medical School and the University Hospitals of Cleveland , Cleveland, Ohio. Received for publication Jan. 17, 1978. Reprint requests: Mark A. Mandel, M.D., Department of Plastic and Reconstructive Surgery, University Hospilals of Cleveland, 2065 Adelbert Rd ., Cleveland. OH 44106.
458
THE JOURNAL OF HAND SURGERY
cellular immunity in diabetic patients. The findings indicate that lymphocytes from patients with diabetes have a diminished ability to respond to nonspecific mitogenic agents, such as phytohemaggutinin.
Clinical studies In the 3 years from 1973 to 1976, 12 patients with severe pyogenic hand infections were treated at the University Hospitals of Cleveland. Each patient was followed for at least 1 year after resolution of the inflammatory process. Therapeutic principles. Treatment of the clinical infections consisted of incision and drainage under either general or axillary block anesthesia, use of large doses of antibiotics, and elevation of the affected extremity . 9- lIThe bulky splinted dressing was changed daily, the wound debrided, and the defect closed when the tissues appeared to be healthy, usually 3 to 7 days after drainage .!2 Inflammatory processes in the following areas were treated: web space (two patients), deep palmar (seven patients), tenosynovitis (two patients), and ulnar bursa (one patient). The cause of the abscess, in most cases, was a puncture wound (Table I). Patients with human bites and superficial infections of the epithelium (paronychia) were excluded from this study. Evaluation of patients for diabetes mellitus. After resolution of the inflammation, all patients were evaluated for diabetes. A clinical history of polydypsia, polyphasia , and polyuria suggested diabetes. 13 • 14 The finding of glucose in the urine and elevated blood levels confirmed the diagnosis. All patients had fasting blood sugar (FBS) (normal, 70 to 110 mg%) and 2 hour postprandial blood sugar (2 hour PP) (normal, less than
0363·5023/78/0503-0458$00.40/0 © 1978 American Society for Surgery of the Hand
Vol. 3, No.5 September, 1978
110 mg%) levels detennined. If the 2 hour PP was elevated, a formal 3 hour oral glucose tolerance test (OTT) was performed . Each patient were classified on the basis of his or her stage of carbohydrate decompensation . The following classification was used: (I) Overt or clinical diabetes: this is frank diabetes with elevated fasting and random blood glucose level; symptoms of hyperglycemia and glycosuria may be present. (2) Chemical or latent diabetes: this is asymptomatic diabetes in which the FBS or 2 hour PP is elevated . The oral OTI in the absence of stress will confirm the diagnosis. (3) Latent or stress diabetes: this is present in those with a nonnal OTT but known to be "diabetic under stressed conditions" (i .e ., pregnancy, infection, burns, myocardial infarction). Other laboratory detenninations perfonned on each patient included standard blood, electrolyte, and liver function tests. Testing of cellular immunity Patients were tested with a sensitizing dose of 2,000 IJ-g of DNCB* in 0.1 ml of acetone; this was applied topically to the skin on the volar aspect of the right foreann within a polyethylene ring 2 cm in diameter. After the acetone evaporated, this site was covered with a light occlusive dressing . Two weeks later each patient was challenged by the topical application of 100 IJ-g of DNCB in 0.1 ml of acetone on the volar aspect of the left forearm, and the site was covered with a light dressing . Daily inspection over the next 4 days revealed the extent of the cutaneous reaction . These were graded as follows: NR, no reaction; +, erythema; + +, erythema plus induration; + + +, erythema plus vesiculation; + + + + erythema , plus ulceration. All tests with reactivity of + + + or greater were considered to be indicative of a delayed cutaneous hypersensitivity to DNCB . (Stock solutions of DNCB were prepared each week and stored in the refrigerator in amber bottles.) Each patient studied was tested also with several antigens administered intradermally (0 . 1 milinjection). Intermediate-strength tuberculin purified protein derivative (Parke, Davis and Co., Detroit, Mich.), coccidioidin I: 100 (Cutter Laboratories, Inc., Berkeley, CaliL), histoplasmin I: 100 (Parke, Davis and Co. , Detroit, Mich.), mumps antigen (0.1 mg) (Eli Lilly and Co. , Indianapolis, Ind.) , and Candida albicans extract (Hollister-Stier Laboratories, Spokane , Wash.) were tested. Patients were injected also with streptokinasestreptodornase (Varidase, Lederle Laboratories, Pearl River, N. Y.). Skin tests were read at 24, 48, and 72 *K and K Laboratories.
Pyogenic hand infections and diabetes mellitus
459
Table I. Relationship between site of inflammation and diabetic state*
Patient
Age (yr)
GM
59
WH
47
LG
53
PM
34
JD
2
DL
19
RM
27
BS
48
DA
17
CV
68
BA
24
JK
52
Site of infiammation Palmar space Palmar space Palmar space Palmar space Palmar space Palmar space Palmar space Tendon sheath Tendon sheath Web space Web space Ulnar bursa
Cause Puncture wound Deep laceration Puncture wound Puncture wound Wood splinter Puncture wound Wood splinter Puncture wound Wood splinter Puncture wound Wood splinter Puncture wound
Diabetic state Overt Overt Latent Latent Normal Normal Normal Latent Normal Overt Normal Latent
"Twelve patients with deep pyogenic hand infections were treated. The age and sex of the patients, site and cause of inflammation , and diabetic state are noted.
hours; they were considered to be positive if the indurated area exceeded 0.5 cm in diameter. Clinical case presentation G. M. , a 59-year-old white man, sustained a small wound of his hand while working at a hardware store on November 7, 1973, 2 days prior to admission . Due to extreme pain in the palm, chills, and fever he came to the emergency room where initial examination showed a massively swollen hand with lymphangitis and large axillary lymph nodes. A small wound of entry was present in the right palm . There was evidence of a pronator space infection . Massive dosages of antibiotics were given9-" and drainage of the entire midpalmar and pronator spaces was performed. 12 The carpal tunnel w.as decompressed and the median nerve and flexor tendons were explored . Large amounts of purulent material were found from which staphylococci were obtained . The wound was dressed at least twice a day and rapid resolution of the inflammation resulted. Five days later wound closure was performed. At the time of admission there was 3 ± glycosuria and a random blood sugar of 192 mg%. Examinations done I week and I month after delayed primary closure showed persistent elevation in the FBS and 2 hour PP. An oral OTT was per-
460
The Journal of HAND SURGERY
Mandel
Table 11* Patient
Candida
GM LG DL
59
CV
68 52
JK
53 19
Oven Latent
Normal Oven Latent
+++ +++ ++++ +++ +++
+++ ++ ++++ +++ +++
+ +
+
+
+
+
+ +
Legend: DNCB, dinitrochlorobenzene . PPD, purified protein derivative. • Five patients with pyogenic hand infections were tested with skin antigens following resolution of the inflammatory process. Regardless of the diabetic state, all patients responded to both the neoantigen, DNCB, and Varidase (streptokinase-streptodornase). A variable response was seen when they were tested with other commonly found antigens. The DNCB and varidase reactions were graded on a 0 to + + + + scale, while the other antigens were scored as either positive or negative.
formed and the result was consistent with a diagnosis of diabetes mellitus. The patient was able to return to work I month after wound closure . However, parethesias in the median nerve distribution persisted for 18 months following injury. Nerve conduction studies performed in July 3D, 1976, 2 years and 8 months after injury, were within normal limits (distal latency period of 3.8 seconds and conduction velocity of 58 .6). The patient's diabetes has been controlled by dietary measures and now he is able to use his hand without difficulty.
Results The following areas were involved in deep infections of the hand: web space (two patients), deep palmar (seven patients), tenosynovitis (two patients), and ulnar bursa (one patient). Three patients were found to have overt clinical diabetes, as evidenced by elevated FBS and clinical symptoms. Four patients had chemical or latent diabetes; each of these had a normal FBS but abnormal OTT, and all were asymptomatic until infection occurred. Five patients had no evidence of diabetes. A summary of the clinical results is shown in Table I. Five patients were evaluated for immune competence utilizing a battery of common skin antigens as well as the neoantigen ONCB. t5 The results of the testing indicate that all patients responded to some of the skin antigens and to the ONCB . One adolescent male patient developed a severe reaction to the ONCB; this was treated with topical steroids. The results of the skin test are seen in Table II.
Discussion Diabetes mellitus is a common metabolic disorder characterized by an inappropriate elevation of the blood glucose and associated with alterations in lipid and protein metabolism due to either a relative or absolute lack of insulin. 13 The cause of this condition remains unknown at the present time. Patients with diabetes appear to have a high incidence of infection. The rhe-
tori cal question is raised as to whether uncontrolled diabetes renders the diabetic patient more susceptible to infection ..; The key point, however, is that, if diabetes is diagnosed, it should be treated properly to avoid major problems. 14 • 16 The current study found a high incidence of either overt or subclinical diabetes in a group of 12 patients with severe, deep hand infections. Only one patient was diagnosed as having diabetes mellitus prior to the infection. This high incidence necessitates careful examination of the blood glucose levels in all patients presenting in this fashion. A delayed study should be performed after resolution of infection, since spuriously high levels can be found during the inflammatory process . If persistent elevation in the FBS and 2 hour PP are found at the time of delayed testing, then an oral glucose tolerance test will be needed to determine if, indeed, subclinical diabetes exists . The aggressive management of hand infections, especially in patients with diabetes, has been stressed by Mann, Hoffeld, and Farmer. 16 Early surgical intervention and massive doses of antibiotics were necessary to prevent serious problems and to improve residual function in patients presenting with diabetes complicating their hand infections. Although amputation was not necessary in any of the patients presented in this report , the principles of early definitive control of the inflammation are stressed. The testing of immune competence in the patients with hand infections was performed at a time when no acute inflammation was present. Those patients who had overt diabetes were controlled using either dietary or chemical means. Thus, although the data from the skin tests implied little difference between the normal patients and those with a hand infection, the unknown factor is whether or not immune competence was depressed at the time of the infection. This would have led to a more severe infectious process than would be found in the "normal" patient. Although depression of
Vol. 3, No.5 September, 1978
DNCB reactivity is a well known factor in patients with neoplastic disorders, especially those of the head and neck area, it well may be that its sensitivity is not adequate to guage immune functions in these borderline, immunologically incompetent patients. 15 The in vitro tissue culture assays indicated significant depression in the mitogenic response of diabetic patients to antigens such as phytohemagglutinin; however, it must be remembered that these lymphocytes were harvested from patients who were either ketotic or in extremely poor metabolic control. 3 When the diabetes became controlled in the patients, the lymphocyte reactivity returned toward normal.
Conclusion Twelve patients were treated for severe pyogenic hand infections. After resolution of inflammation, all patients were evaluated for diabetes. Three patients were found to have overt diabetes, as evidenced by elevated FBS and clinical symptoms; four patients had latent diabetes with normal FBS but an abnormal glucose tolerance curve. This was a disproportionately high incidence of metabolic disorders for this series. U sing cutaneous reacti vity as a quantitati ve measure of immune competence, all patients were found to be normal in their response. Further elucidation of immune competence therefore will have to rely upon more sophisticated methods of immune testing. It can be concluded, however, that in the presence of a pyogenic hand infection, it is advantageous to test the patient either immediately or in a delayed fashion for the presence of diabetes mellitus so that appropriate patient management can be undertaken. REFERENCES
Pyogenic hand infections and diabetes mellitus
3.
4.
5.
6.
7.
8.
9. 10. II.
12. 13.
14.
15.
I. Johnson JE III: Infection and diabetes, in Ellenberg M,
Rifkin H, editors: Diabetes mellitus: Theory and practice, New York, 1970, McGraw-Hill Book Co, Inc, pp 734-45 2. Bybee 10, Rogers DR: The phagocytic activity of poly-
16.
461
morphonuclear leukocytes obtained from patients with diabetes mellitus. J Lab Clin Med 64:1-13,1964 Bagdade JE, Root RK, Bulger RJ: Impaired leukocyte function in patients with poorly controlled diabetes. Diabetes 23:9-15, 1974 Mowat AG, Baum J: Chemotaxis of polymorphonuclear leukocytes from patients with diabetes mellitus. N Engl J Med 284:621-7, 1971 Robertson HD, Polk HC Jr: The mechanism of infection in patients with diabetes mellitus: A review of leukocyte malfunction. Surgery 75:123-8, 1974 Brody 11, Merlie K: Metabolic and biosynthetic features of lymphocytes from patients with diabetes mellitus: Similarities to lymphocytes in chronic lymphocytic leukemia. Br J Hematol 19: 193-201, 1970 Dolkart RE, Halpern B, Perlman J: Comparison of antibody responses in normal and alloxan diabetic mice. Diabetes 20: 162-7, 1971 MacCuish AC, Urbaniak SJ, Campbell CJ, et al: Phytohemagglutinin transformation and circulating lymphocyte subpopulations in insulin dependent diabetic patients. Diabetes 23:708-12, 1974 Chuinard RG, D'Ambrosia RD: Human bite infections of the hand. J Bone Joint Surg [AM] 59:416-8, 1977 Nicholls RJ: Initial choice of antibiotic treatment for pyogenic hand infections. Lancet 1:225-6, 1973 Stone N, Hursch H, Humphrey C, et al: Empirical selection of antibiotics for hand infections. J Bone Joint Surg [AM] 51:899-903, 1969 Kanavel AB: Infections of the hand, ed 6, Philadelphia, 1933, Lea & Febiger, Publishers Steinke J, Thorn GW: Diabetes mellitus, in Wintrobe MD, Thorn GW, Adams RD, et ai, editors: Harrison's principles of internal medicine, New York, 1974, McGraw-Hill Book Co, pp. 532-4 Fajans SS, Sussman KE: Diabetes mellitus: Diagnosis and treatment. New York, 1971, American Diabetes Association Mandel MA: Skin testing for prognosis or therapy formulation in cancer patients: Caveat emptor. Plast Reconstr Surg 57:621-6, 1976 Mann RJ, Hoffeld TA, Farmer CB: Human bites of the hand: Twenty years of experience. J HAND SURG 2:97104, 1977
Mark A. Mandel, M.D., Cleveland, Ohio
Patients with diabetes mellitus have an increased susceptibility to some infectious agents; an immune basis for this altered response has not been defined as yet. In the present study 12 patients with deep pyogenic hand infections treated during a 4 year interval were evaluated for diabetes mellitus. Cellular immunity was assessed by the intradermal injection of common antigens and the topical application of dinitrochlorobenzene (DNCB). Prior to insulin treatment, infectious diseases, especially those of mycotic origin, were a major cause of death in patients with diabetes.! It long has been suspected that patients with diabetes have an impaired ability to combat infections. Diabetic patients, when ketotic ,2. 3 have been found to have impaired phagocytosis and to have altered white cell chemotactic ability.4 Alteration in the metabolic pathways of patients with diabetes appears to be responsible for leukocyte dysfunction. 5 • 6 Humoral immunity in diabetic animals, on the other hand, does not seem to be impaired. 7 The surface immunoglobulins in both diabetic and normal white cells appear to be similar. 4 Few studies on cellular immunity in patients with diabetes have been published. In 1974, MacCuish and co-workers8 reported the first quantitative evaluation of
From the Department of Surgery, Division of Plastic Surgery, Case Western Reserve University Medical School and the University Hospitals of Cleveland , Cleveland, Ohio. Received for publication Jan. 17, 1978. Reprint requests: Mark A. Mandel, M.D., Department of Plastic and Reconstructive Surgery, University Hospilals of Cleveland, 2065 Adelbert Rd ., Cleveland. OH 44106.
458
THE JOURNAL OF HAND SURGERY
cellular immunity in diabetic patients. The findings indicate that lymphocytes from patients with diabetes have a diminished ability to respond to nonspecific mitogenic agents, such as phytohemaggutinin.
Clinical studies In the 3 years from 1973 to 1976, 12 patients with severe pyogenic hand infections were treated at the University Hospitals of Cleveland. Each patient was followed for at least 1 year after resolution of the inflammatory process. Therapeutic principles. Treatment of the clinical infections consisted of incision and drainage under either general or axillary block anesthesia, use of large doses of antibiotics, and elevation of the affected extremity . 9- lIThe bulky splinted dressing was changed daily, the wound debrided, and the defect closed when the tissues appeared to be healthy, usually 3 to 7 days after drainage .!2 Inflammatory processes in the following areas were treated: web space (two patients), deep palmar (seven patients), tenosynovitis (two patients), and ulnar bursa (one patient). The cause of the abscess, in most cases, was a puncture wound (Table I). Patients with human bites and superficial infections of the epithelium (paronychia) were excluded from this study. Evaluation of patients for diabetes mellitus. After resolution of the inflammation, all patients were evaluated for diabetes. A clinical history of polydypsia, polyphasia , and polyuria suggested diabetes. 13 • 14 The finding of glucose in the urine and elevated blood levels confirmed the diagnosis. All patients had fasting blood sugar (FBS) (normal, 70 to 110 mg%) and 2 hour postprandial blood sugar (2 hour PP) (normal, less than
0363·5023/78/0503-0458$00.40/0 © 1978 American Society for Surgery of the Hand
Vol. 3, No.5 September, 1978
110 mg%) levels detennined. If the 2 hour PP was elevated, a formal 3 hour oral glucose tolerance test (OTT) was performed . Each patient were classified on the basis of his or her stage of carbohydrate decompensation . The following classification was used: (I) Overt or clinical diabetes: this is frank diabetes with elevated fasting and random blood glucose level; symptoms of hyperglycemia and glycosuria may be present. (2) Chemical or latent diabetes: this is asymptomatic diabetes in which the FBS or 2 hour PP is elevated . The oral OTI in the absence of stress will confirm the diagnosis. (3) Latent or stress diabetes: this is present in those with a nonnal OTT but known to be "diabetic under stressed conditions" (i .e ., pregnancy, infection, burns, myocardial infarction). Other laboratory detenninations perfonned on each patient included standard blood, electrolyte, and liver function tests. Testing of cellular immunity Patients were tested with a sensitizing dose of 2,000 IJ-g of DNCB* in 0.1 ml of acetone; this was applied topically to the skin on the volar aspect of the right foreann within a polyethylene ring 2 cm in diameter. After the acetone evaporated, this site was covered with a light occlusive dressing . Two weeks later each patient was challenged by the topical application of 100 IJ-g of DNCB in 0.1 ml of acetone on the volar aspect of the left forearm, and the site was covered with a light dressing . Daily inspection over the next 4 days revealed the extent of the cutaneous reaction . These were graded as follows: NR, no reaction; +, erythema; + +, erythema plus induration; + + +, erythema plus vesiculation; + + + + erythema , plus ulceration. All tests with reactivity of + + + or greater were considered to be indicative of a delayed cutaneous hypersensitivity to DNCB . (Stock solutions of DNCB were prepared each week and stored in the refrigerator in amber bottles.) Each patient studied was tested also with several antigens administered intradermally (0 . 1 milinjection). Intermediate-strength tuberculin purified protein derivative (Parke, Davis and Co., Detroit, Mich.), coccidioidin I: 100 (Cutter Laboratories, Inc., Berkeley, CaliL), histoplasmin I: 100 (Parke, Davis and Co. , Detroit, Mich.), mumps antigen (0.1 mg) (Eli Lilly and Co. , Indianapolis, Ind.) , and Candida albicans extract (Hollister-Stier Laboratories, Spokane , Wash.) were tested. Patients were injected also with streptokinasestreptodornase (Varidase, Lederle Laboratories, Pearl River, N. Y.). Skin tests were read at 24, 48, and 72 *K and K Laboratories.
Pyogenic hand infections and diabetes mellitus
459
Table I. Relationship between site of inflammation and diabetic state*
Patient
Age (yr)
GM
59
WH
47
LG
53
PM
34
JD
2
DL
19
RM
27
BS
48
DA
17
CV
68
BA
24
JK
52
Site of infiammation Palmar space Palmar space Palmar space Palmar space Palmar space Palmar space Palmar space Tendon sheath Tendon sheath Web space Web space Ulnar bursa
Cause Puncture wound Deep laceration Puncture wound Puncture wound Wood splinter Puncture wound Wood splinter Puncture wound Wood splinter Puncture wound Wood splinter Puncture wound
Diabetic state Overt Overt Latent Latent Normal Normal Normal Latent Normal Overt Normal Latent
"Twelve patients with deep pyogenic hand infections were treated. The age and sex of the patients, site and cause of inflammation , and diabetic state are noted.
hours; they were considered to be positive if the indurated area exceeded 0.5 cm in diameter. Clinical case presentation G. M. , a 59-year-old white man, sustained a small wound of his hand while working at a hardware store on November 7, 1973, 2 days prior to admission . Due to extreme pain in the palm, chills, and fever he came to the emergency room where initial examination showed a massively swollen hand with lymphangitis and large axillary lymph nodes. A small wound of entry was present in the right palm . There was evidence of a pronator space infection . Massive dosages of antibiotics were given9-" and drainage of the entire midpalmar and pronator spaces was performed. 12 The carpal tunnel w.as decompressed and the median nerve and flexor tendons were explored . Large amounts of purulent material were found from which staphylococci were obtained . The wound was dressed at least twice a day and rapid resolution of the inflammation resulted. Five days later wound closure was performed. At the time of admission there was 3 ± glycosuria and a random blood sugar of 192 mg%. Examinations done I week and I month after delayed primary closure showed persistent elevation in the FBS and 2 hour PP. An oral OTT was per-
460
The Journal of HAND SURGERY
Mandel
Table 11* Patient
Candida
GM LG DL
59
CV
68 52
JK
53 19
Oven Latent
Normal Oven Latent
+++ +++ ++++ +++ +++
+++ ++ ++++ +++ +++
+ +
+
+
+
+
+ +
Legend: DNCB, dinitrochlorobenzene . PPD, purified protein derivative. • Five patients with pyogenic hand infections were tested with skin antigens following resolution of the inflammatory process. Regardless of the diabetic state, all patients responded to both the neoantigen, DNCB, and Varidase (streptokinase-streptodornase). A variable response was seen when they were tested with other commonly found antigens. The DNCB and varidase reactions were graded on a 0 to + + + + scale, while the other antigens were scored as either positive or negative.
formed and the result was consistent with a diagnosis of diabetes mellitus. The patient was able to return to work I month after wound closure . However, parethesias in the median nerve distribution persisted for 18 months following injury. Nerve conduction studies performed in July 3D, 1976, 2 years and 8 months after injury, were within normal limits (distal latency period of 3.8 seconds and conduction velocity of 58 .6). The patient's diabetes has been controlled by dietary measures and now he is able to use his hand without difficulty.
Results The following areas were involved in deep infections of the hand: web space (two patients), deep palmar (seven patients), tenosynovitis (two patients), and ulnar bursa (one patient). Three patients were found to have overt clinical diabetes, as evidenced by elevated FBS and clinical symptoms. Four patients had chemical or latent diabetes; each of these had a normal FBS but abnormal OTT, and all were asymptomatic until infection occurred. Five patients had no evidence of diabetes. A summary of the clinical results is shown in Table I. Five patients were evaluated for immune competence utilizing a battery of common skin antigens as well as the neoantigen ONCB. t5 The results of the testing indicate that all patients responded to some of the skin antigens and to the ONCB . One adolescent male patient developed a severe reaction to the ONCB; this was treated with topical steroids. The results of the skin test are seen in Table II.
Discussion Diabetes mellitus is a common metabolic disorder characterized by an inappropriate elevation of the blood glucose and associated with alterations in lipid and protein metabolism due to either a relative or absolute lack of insulin. 13 The cause of this condition remains unknown at the present time. Patients with diabetes appear to have a high incidence of infection. The rhe-
tori cal question is raised as to whether uncontrolled diabetes renders the diabetic patient more susceptible to infection ..; The key point, however, is that, if diabetes is diagnosed, it should be treated properly to avoid major problems. 14 • 16 The current study found a high incidence of either overt or subclinical diabetes in a group of 12 patients with severe, deep hand infections. Only one patient was diagnosed as having diabetes mellitus prior to the infection. This high incidence necessitates careful examination of the blood glucose levels in all patients presenting in this fashion. A delayed study should be performed after resolution of infection, since spuriously high levels can be found during the inflammatory process . If persistent elevation in the FBS and 2 hour PP are found at the time of delayed testing, then an oral glucose tolerance test will be needed to determine if, indeed, subclinical diabetes exists . The aggressive management of hand infections, especially in patients with diabetes, has been stressed by Mann, Hoffeld, and Farmer. 16 Early surgical intervention and massive doses of antibiotics were necessary to prevent serious problems and to improve residual function in patients presenting with diabetes complicating their hand infections. Although amputation was not necessary in any of the patients presented in this report , the principles of early definitive control of the inflammation are stressed. The testing of immune competence in the patients with hand infections was performed at a time when no acute inflammation was present. Those patients who had overt diabetes were controlled using either dietary or chemical means. Thus, although the data from the skin tests implied little difference between the normal patients and those with a hand infection, the unknown factor is whether or not immune competence was depressed at the time of the infection. This would have led to a more severe infectious process than would be found in the "normal" patient. Although depression of
Vol. 3, No.5 September, 1978
DNCB reactivity is a well known factor in patients with neoplastic disorders, especially those of the head and neck area, it well may be that its sensitivity is not adequate to guage immune functions in these borderline, immunologically incompetent patients. 15 The in vitro tissue culture assays indicated significant depression in the mitogenic response of diabetic patients to antigens such as phytohemagglutinin; however, it must be remembered that these lymphocytes were harvested from patients who were either ketotic or in extremely poor metabolic control. 3 When the diabetes became controlled in the patients, the lymphocyte reactivity returned toward normal.
Conclusion Twelve patients were treated for severe pyogenic hand infections. After resolution of inflammation, all patients were evaluated for diabetes. Three patients were found to have overt diabetes, as evidenced by elevated FBS and clinical symptoms; four patients had latent diabetes with normal FBS but an abnormal glucose tolerance curve. This was a disproportionately high incidence of metabolic disorders for this series. U sing cutaneous reacti vity as a quantitati ve measure of immune competence, all patients were found to be normal in their response. Further elucidation of immune competence therefore will have to rely upon more sophisticated methods of immune testing. It can be concluded, however, that in the presence of a pyogenic hand infection, it is advantageous to test the patient either immediately or in a delayed fashion for the presence of diabetes mellitus so that appropriate patient management can be undertaken. REFERENCES
Pyogenic hand infections and diabetes mellitus
3.
4.
5.
6.
7.
8.
9. 10. II.
12. 13.
14.
15.
I. Johnson JE III: Infection and diabetes, in Ellenberg M,
Rifkin H, editors: Diabetes mellitus: Theory and practice, New York, 1970, McGraw-Hill Book Co, Inc, pp 734-45 2. Bybee 10, Rogers DR: The phagocytic activity of poly-
16.
461
morphonuclear leukocytes obtained from patients with diabetes mellitus. J Lab Clin Med 64:1-13,1964 Bagdade JE, Root RK, Bulger RJ: Impaired leukocyte function in patients with poorly controlled diabetes. Diabetes 23:9-15, 1974 Mowat AG, Baum J: Chemotaxis of polymorphonuclear leukocytes from patients with diabetes mellitus. N Engl J Med 284:621-7, 1971 Robertson HD, Polk HC Jr: The mechanism of infection in patients with diabetes mellitus: A review of leukocyte malfunction. Surgery 75:123-8, 1974 Brody 11, Merlie K: Metabolic and biosynthetic features of lymphocytes from patients with diabetes mellitus: Similarities to lymphocytes in chronic lymphocytic leukemia. Br J Hematol 19: 193-201, 1970 Dolkart RE, Halpern B, Perlman J: Comparison of antibody responses in normal and alloxan diabetic mice. Diabetes 20: 162-7, 1971 MacCuish AC, Urbaniak SJ, Campbell CJ, et al: Phytohemagglutinin transformation and circulating lymphocyte subpopulations in insulin dependent diabetic patients. Diabetes 23:708-12, 1974 Chuinard RG, D'Ambrosia RD: Human bite infections of the hand. J Bone Joint Surg [AM] 59:416-8, 1977 Nicholls RJ: Initial choice of antibiotic treatment for pyogenic hand infections. Lancet 1:225-6, 1973 Stone N, Hursch H, Humphrey C, et al: Empirical selection of antibiotics for hand infections. J Bone Joint Surg [AM] 51:899-903, 1969 Kanavel AB: Infections of the hand, ed 6, Philadelphia, 1933, Lea & Febiger, Publishers Steinke J, Thorn GW: Diabetes mellitus, in Wintrobe MD, Thorn GW, Adams RD, et ai, editors: Harrison's principles of internal medicine, New York, 1974, McGraw-Hill Book Co, pp. 532-4 Fajans SS, Sussman KE: Diabetes mellitus: Diagnosis and treatment. New York, 1971, American Diabetes Association Mandel MA: Skin testing for prognosis or therapy formulation in cancer patients: Caveat emptor. Plast Reconstr Surg 57:621-6, 1976 Mann RJ, Hoffeld TA, Farmer CB: Human bites of the hand: Twenty years of experience. J HAND SURG 2:97104, 1977
