British Journal of Dermatology {i^^s) 92, 625.
Viral warts^ herpes simplex and herpes zoster in patients with secondary immune deficiencies and neoplasms WARWICK L.MORISON* Department of Dermatology, St Helier Hospital, Carshalton, Surrey Accepted for publication 30 September 1974
SUMMARY
The incidence of viral warts, recurrent herpes simplex and herpes zoster has been assessed in a group of patients with possible secondary immune deficiency states and compared to a control group. Patients with cell-mediated immune deficiency appear to be more prone to warts and zoster infection as compared to patients with humoral immune deficiency. Recurrent herpes simplex infection was not increased in either group.
The central aim of the present study was to determine whether there is a difference in the incidence of viral warts in patients with cell-mediated immune deficiency as compared to patients with humoral immune deficiency. If there is a difference, this may give an indication as to which immimological mechanism is important in controlling this infection. It was felt that it would be interesting to compare and contrast the incidence of recurrent herpes simplex and of herpes zoster in the same patients as, particularly in the case of zoster, an association with immime deficiency has long been known. A report (Hoon & Ansfield, 1964) that viral warts are less common in patients with systemic malignancy prompted the third part of the study; the assessment of the incidence of these three viral infections in patients with cutaneous and systemic neoplasms. The incidence of warts, herpes simplex and zoster was also assessed in a control group to establish a baseline for comparison. Selection of patients The main problem in a study such as this is to find a sufficiently large group of patients who are immune deficient. Congenital immune deficiency states were not available in sufficient numbers and therefore the secondary immune deficiency states had to be used. No attempt was made to investigate the immime function of the patients in this study although only, patients with a definite histological diagnosis of the underlying disorder were included. The disease categories selected were: multiple myeloma as an example of humoral immune deficiency; Hodgkin's disease as an example of cell-mediated immune deficiency; chronic lymphatic leukaemia (C.L.L.) as a disease showing features of both forms of immune deficiency. In addition * Present address: St John's Hospital, Leicester Square, London 625
626
Warwick L.Morison
patients with malignant lymphomas were examined although it was realized that any immune defect in this heterogeneous group is poorly defined; however most studies so far have indicated a cellmediated immune deficiency, at least in some patients, with malignant lymphomas. In all these conditions, chemotherapy and radiotherapy superimpose a further immune defect. There is such a wide variety of drugs and doses of radio-therapy used, largely with unexplored effects on immunity, that it was felt that this infiuence would be impossible to control. Instead patients were questioned as to the time relationship of infection to treatment, and time intervals, as documented in case notes, were taken into account. MATERIALS AND METHODS
A group of 633 patients and 348 control subjects were questioned and examined; their diagnoses, age and disease duration are shown in Table i. The group of patients listed as systemic malignancy TABLE I .
Number Age Disease duration
Details of patients and controls
Multiple myeloma
Hodgkin's disease
Malignant lymphoma
C.L.L.
78 60 3
159 35 4
i«J9 14 4.
51 63 4
Systemic malignancy 156 56 25
B.C.C.
Controls
80 60 2
348 44
B.C.C, basal cell carcinoma of the skin; C.L.L., chronic lymphatic leukaemia.
consisted of carcinomas and sarcomas of various types. The control subjects were seen in a hospital casualty department. They were selected in so far as they were casualties, patients with significant systemic disease being excluded. All patients and controls were over the age of 17 years as inclusion of children would lead to confusing results, particularly in respect of viral warts. Each person was personally interviewed by the author and details recorded on a standard question sheet. It was first established that the individual understood what the terms, wart or verruca, herpes simplex or cold sores, herpes zoster or shingles, meant, and then details regarding the infections were sought. Lesions stated to be warts were examined, as well as any other lesion mentioned by the patient. Subjects not having an adequate understanding of the English language or who were imable to comprehend the questions due to age or illness were excluded. The term herpes simplex was used mainly in reference to cold sores and no attempt was made to ascertain the incidence of herpes simplex in other areas of the body. RESULTS
Present viral warts The results are shown in Table 2. It can be seen that patients with Hodgkin's disease, malignant lymphoma or chronic lymphatic leukaemia have a considerably increased incidence of warts. The average number of warts as compared to controls is also increased, and in the majority of afifected patients with these conditions, the warts preceded the onset of symptoms from the underlying disease. Four patients with Hodgkin's disease, one with lymphoma and one with C.L.L. had had warts successfully removed since the onset of their disease. However, although over 50% of the patients with
Dermatoses in secondary immune deficiency states
627
TABLE 2. Incidence of present viral wart infections
Control subjects Multiple myeloma Hodgkin's disease Malignant Iymphoma C.L.L. Systemic malignancy B.C.C.
Incidence
Incidence before treatment
(%)
(%)
Mean number of warts 1
23 0
296 20-1 176 45
6
m t*
16 16
i
8
r
62
warts were receiving treatment for their warts, no others had had any success in eradicating them. Five patients related the appearance of their warts to chemotherapy or radiotherapy, while two had noted considerable reduction in the number of their warts with chemotherapy. The site and type of warts were noted. No particular localization was found although, surprisingly, no cases of ano-genital warts were seen in this survey. Plane warts were by far the most common type in patients with Hodgkin's-lymphoma-leukaemia, particularly in those having a great number of warts. Past viral warts
There were no outstanding differences in the various conditions either over the whole of the lifetime of the patients or after the age of 20 years. Recurrent herpes simplex
The incidence of this infection is given in Table 3. It can be seen that patients with multiple myeloma and systemic malignancy have a much lower incidence as compared to both the control group and patients with other neoplasms. There is a predominance of males, particularly in the control group. The frequency of recurrences of herpes simplex was also recorded and patients were asked whether TABLE 3 . Incidence of herpes simplex infection Incidence Control subjects Multiple myeloma Hodgkin's disease Malignant Iymphoma C.L.L. Systemic malignancy B.C.C.
(%)
Male/female
39 39
102/34 12/4 36/23
42
26/20
21
39
14/6
23
20/16 16/12
35
they thought that attacks were more or less frequent over the past 5-10 years. Nineteen patients with a malignancy or Iymphoma had noted an increased frequency of attacks since diagnosis of their underlying disease and all related the increase to treatment.
628
Warwick L.Morison
Herpes zoster The incidence of this infection is given in Table 4. Herpes zoster is more common in patients with Hodgkin's disease, malignant lymphoma and C.L.L. as compared to the other groups and controls. The increased incidence is mainly accounted for by attacks occurring after the onset of the disease. It is interesting that five patients with lymphomas gave a history of two separate episodes of zoster infection. TABLE 4. Incidence of herpes zoster infection
Incidence (%)
Controls Multiple myeloma Hodgkin's disease Malignant lymphoma C.L.L. Systemic malignancy B.C.C.
Cases occurring after onset of disease (7o)
II
m
38 =26 2f: 13 15
8 68 46 64 30 8
DISCUSSION
Viral warts This survey shows a greatly increased incidence of warts in patients with Hodgkin's disease and a lesser but still marked increase in patients with C.L.L. and malignant lymphoma. As explained earlier, this group are at least to some degree deficient in cell-mediated immunity. In contrast, patients with multiple myeloma do not show an increased incidence of warts and these patients are, if anything, deficient in humoral antibody responses. The increase of warts in the Hodgkin's-lymphomaleukaemia group is not just due to treatment because the incidence had risen before any treatment had been given and, furthermore, myeloma patients also receive chemotherapy and radiotherapy. The results of this survey suggest that patients with cell-mediated immune deficiency are prone to wart infection while those with humoral immune deficiency are not. Furthermore, once a patient with such a deficiency develops warts they are unlikely to resolve spontaneously or to show a satisfactory response to conventional therapy. It is therefore suggested that cell-mediated immune responses are an important factor both in preventing warts and in bringing about their successful resolution. In addition it is suggested that humoral antibodies are not important in preventing wart infection. Only one previous survey of warts in immune deficient patients could be found in the literature (Spencer & Anderson, 1970). They found that 42% of fifty-five renal transplant patients developed warts within a year of transplantation. Prednisone and azathioprine, used for immunosuppression in their patients, particularly depresses cell-mediated immunity and therefore that study would appear to support the present results. Patients with systemic and cutaneous malignancy of the carcinoma-sarcoma variety do not appear to be different from the control group so far as the incidence of warts is concerned. Therefore this survey does not support the suggestion of a reduced incidence of warts in patients with carcinoma (Hoon & Ansfield, 1964).
Dermatoses in secondary immune deficiency states
629
Recurrent herpes simplex
Two interesting findings emerge from this part of the study. Firstly, the low incidence of herpes simplex found in patients with myeloma and systemic malignancy. A recent survey (Ross & Tyrrell, 1974) among patients with carcinoma of the lung found a very similar result, 21% of patients having a history of herpes simplex infection as against 42% of the controls. The authors suggested that recurrent herpes simplex raises the level of immunity to malignancy by stimulating immunological surveillance. However if this was the case the Hodgkin's-lymphoma-leukaemia group, which are also malignancies, might be expected to show a reduced incidence, but in the present study they differ little from the controls. The second interesting finding is that there is no indication from this survey that immunological factors are important in determining the incidence of recurrent herpes simplex. The role of immune function in this infection in humans is at present poorly defined. That humoral antibodies alone play no significant part has been established (Douglas & Couch, 1970) but the importance of cell-mediated immunity is debatable. Severe herpes simplex has been reported in renal transplant patients (Montgomerie et al., 1969) but the four patients discussed also had cytomegalovirus in their lesions, a virus now known to cause severe infections in immuno-suppressed patients (Lopez et al., 1973). The Wiskott-Aldrich syndrome is another disease reported (Cooper et al., 1968) to show an increased incidence and severity of herpes simplex infection. However patients with this syndrome also have eczema, which can of course lead to widespread herpes simplex infection in the absence of any demonstrable immune defect. Two surveys (Spencer & Anderson, 1970; Rifkind, 1964) as opposed to case reports, have found that the incidence and severity of recurrent herpes simplex is not increased in immuno-suppressed renal transplant patients. An increase in frequency of attacks was noted in all disease groups by at least some patients in the present study and was usually attributed to treatment. This increase is probably not due to an immune disturbance, but instead, could arise from non-specific factors such as debility, operating in a similar manner to coryza and sunlight, both well-known precipitants of herpes simplex infection. Herpes zoster
The association of herpes zoster and malignancy has long been recognized and has been analysed in many different ways, but this appears to be the first survey to look at the incidence from the viewpoint of the immune state of the patients. There is a considerable increase in the incidence of zoster in the Hodgkin's-lymphoma-leukaemia groups and this increase is mainly accounted for by cases occurring after the onset of the disease. Therefore treatment may have an infiuence here. However myeloma patients also receive similar immuno-suppressive treatment and they do not show this increase after the onset of the disease. In fact, even though the myeloma patients are in an older age group than the controls, they show little increase in the incidence of zoster infection. As with warts, the present survey showed that the most marked increase in the incidence of zoster occurs in patients with some degree of cell-mediated immune deficiency while those having only a humoral immune deficiency show little increase. It is therefore possible that the prevention of herpes zoster is a function of cell-mediated immune responses. , CONCLUSIONS
(i) The incidence of viral warts is increased in patients with: Hodgkin's disease Malignant lymphoma Chronic lymphatic leukaemia
630
Warwick L.Morison
(2) The incidence of herpes zoster is increased in patients with: Hodgkin's disease Malignant lymphoma Chronic lymphatic letikaemia (3) This study suggests that: (a) Cell-mediated immunity may be important in both the prevention and resolution of infections due to wart virus. (b) Cell-mediated immtinity may be important in preventing infections due to varicella-zoster virus. (c) Immunological factors are not important in preventing recurrent herpes simplex infections. ACKNOWLEDGMENTS
The Author wishes to thank the people who made this survey possible by their help and co-operation, Drs T.J.McElwain and M.J.Peckham of the Royal Marsden Hospital, Sutton; Dr E.Wiltshaw of the Royal Marsden Hospital, Fultham; Professor G.H.Fairley of St Bartholomew's Hospital; Professor G.Wetherley-Mein and Dr C.D.Collins of St Thomas' Hospital; and all the consultants at St Helier Hospital. St John's Hospital Medical Illustration Department kindly provided the illustrations. This work was made possible by a grant from the S.W. Metropolitan Regional Hospital Board. REFERENCES COOPER, M.D., CHASE, H.P., LOWMAN, J.T., KRIVIT, W . & GOOD, R . A . (1968) Wiskott-Aldrich Syndrome.
American Journal of Medicine, 44, 499. DOUGLAS, R . G . & COUCH, R . B . (1970) A prospective study of chronic herpes infection and recurrent herpes labialis in humans. Journal of Immunology, 104, 289. HOON, J.R. & ANSFIELD, F.J. (1964) Interference between verruca vulgaris and malignant growths in humans. Annals of the New York Academy of Science, 118, 453. LOPEZ, C , SIMMONS, R.L., MAUER, M . , PARK, B., NATARIAN, J . S . & GOOD, R.A. (1973) Role of virus infections
in immuno-suppressed renal transplant patients. Transplantation Proceedings, 5, 803. MoNTGOMERiE, J.Z., BECROFT, D.M.O., CROXSON, M . C , DOAK, P . B . & NORTH, J . D . K . (1969) Herpes simplex
virus infection after renal transplantation. Lancet, ii, 867. RiFKiND, D. (1964) Infectious diseases associated with renal transplantation. In: Experiences in Renal Transplantation (Ed. by T.E.Starzl), p. 213. Saunders, Philadelphia and London. Ross, C.A.C. & TYRRELL, W . F . (1974) Possible prevention of bronchial carcinoma by recurrent herpes simplex. Lancet, i, 871. SPENCER, E . S . & ANDERSON, H . K . (1970) Clinically evident, non-terminal infections with herpes virus and wart virus in immuno-suppressed renal allograft recipients. British Medical Journal, 3, 251.
Viral warts^ herpes simplex and herpes zoster in patients with secondary immune deficiencies and neoplasms WARWICK L.MORISON* Department of Dermatology, St Helier Hospital, Carshalton, Surrey Accepted for publication 30 September 1974
SUMMARY
The incidence of viral warts, recurrent herpes simplex and herpes zoster has been assessed in a group of patients with possible secondary immune deficiency states and compared to a control group. Patients with cell-mediated immune deficiency appear to be more prone to warts and zoster infection as compared to patients with humoral immune deficiency. Recurrent herpes simplex infection was not increased in either group.
The central aim of the present study was to determine whether there is a difference in the incidence of viral warts in patients with cell-mediated immune deficiency as compared to patients with humoral immune deficiency. If there is a difference, this may give an indication as to which immimological mechanism is important in controlling this infection. It was felt that it would be interesting to compare and contrast the incidence of recurrent herpes simplex and of herpes zoster in the same patients as, particularly in the case of zoster, an association with immime deficiency has long been known. A report (Hoon & Ansfield, 1964) that viral warts are less common in patients with systemic malignancy prompted the third part of the study; the assessment of the incidence of these three viral infections in patients with cutaneous and systemic neoplasms. The incidence of warts, herpes simplex and zoster was also assessed in a control group to establish a baseline for comparison. Selection of patients The main problem in a study such as this is to find a sufficiently large group of patients who are immune deficient. Congenital immune deficiency states were not available in sufficient numbers and therefore the secondary immune deficiency states had to be used. No attempt was made to investigate the immime function of the patients in this study although only, patients with a definite histological diagnosis of the underlying disorder were included. The disease categories selected were: multiple myeloma as an example of humoral immune deficiency; Hodgkin's disease as an example of cell-mediated immune deficiency; chronic lymphatic leukaemia (C.L.L.) as a disease showing features of both forms of immune deficiency. In addition * Present address: St John's Hospital, Leicester Square, London 625
626
Warwick L.Morison
patients with malignant lymphomas were examined although it was realized that any immune defect in this heterogeneous group is poorly defined; however most studies so far have indicated a cellmediated immune deficiency, at least in some patients, with malignant lymphomas. In all these conditions, chemotherapy and radiotherapy superimpose a further immune defect. There is such a wide variety of drugs and doses of radio-therapy used, largely with unexplored effects on immunity, that it was felt that this infiuence would be impossible to control. Instead patients were questioned as to the time relationship of infection to treatment, and time intervals, as documented in case notes, were taken into account. MATERIALS AND METHODS
A group of 633 patients and 348 control subjects were questioned and examined; their diagnoses, age and disease duration are shown in Table i. The group of patients listed as systemic malignancy TABLE I .
Number Age Disease duration
Details of patients and controls
Multiple myeloma
Hodgkin's disease
Malignant lymphoma
C.L.L.
78 60 3
159 35 4
i«J9 14 4.
51 63 4
Systemic malignancy 156 56 25
B.C.C.
Controls
80 60 2
348 44
B.C.C, basal cell carcinoma of the skin; C.L.L., chronic lymphatic leukaemia.
consisted of carcinomas and sarcomas of various types. The control subjects were seen in a hospital casualty department. They were selected in so far as they were casualties, patients with significant systemic disease being excluded. All patients and controls were over the age of 17 years as inclusion of children would lead to confusing results, particularly in respect of viral warts. Each person was personally interviewed by the author and details recorded on a standard question sheet. It was first established that the individual understood what the terms, wart or verruca, herpes simplex or cold sores, herpes zoster or shingles, meant, and then details regarding the infections were sought. Lesions stated to be warts were examined, as well as any other lesion mentioned by the patient. Subjects not having an adequate understanding of the English language or who were imable to comprehend the questions due to age or illness were excluded. The term herpes simplex was used mainly in reference to cold sores and no attempt was made to ascertain the incidence of herpes simplex in other areas of the body. RESULTS
Present viral warts The results are shown in Table 2. It can be seen that patients with Hodgkin's disease, malignant lymphoma or chronic lymphatic leukaemia have a considerably increased incidence of warts. The average number of warts as compared to controls is also increased, and in the majority of afifected patients with these conditions, the warts preceded the onset of symptoms from the underlying disease. Four patients with Hodgkin's disease, one with lymphoma and one with C.L.L. had had warts successfully removed since the onset of their disease. However, although over 50% of the patients with
Dermatoses in secondary immune deficiency states
627
TABLE 2. Incidence of present viral wart infections
Control subjects Multiple myeloma Hodgkin's disease Malignant Iymphoma C.L.L. Systemic malignancy B.C.C.
Incidence
Incidence before treatment
(%)
(%)
Mean number of warts 1
23 0
296 20-1 176 45
6
m t*
16 16
i
8
r
62
warts were receiving treatment for their warts, no others had had any success in eradicating them. Five patients related the appearance of their warts to chemotherapy or radiotherapy, while two had noted considerable reduction in the number of their warts with chemotherapy. The site and type of warts were noted. No particular localization was found although, surprisingly, no cases of ano-genital warts were seen in this survey. Plane warts were by far the most common type in patients with Hodgkin's-lymphoma-leukaemia, particularly in those having a great number of warts. Past viral warts
There were no outstanding differences in the various conditions either over the whole of the lifetime of the patients or after the age of 20 years. Recurrent herpes simplex
The incidence of this infection is given in Table 3. It can be seen that patients with multiple myeloma and systemic malignancy have a much lower incidence as compared to both the control group and patients with other neoplasms. There is a predominance of males, particularly in the control group. The frequency of recurrences of herpes simplex was also recorded and patients were asked whether TABLE 3 . Incidence of herpes simplex infection Incidence Control subjects Multiple myeloma Hodgkin's disease Malignant Iymphoma C.L.L. Systemic malignancy B.C.C.
(%)
Male/female
39 39
102/34 12/4 36/23
42
26/20
21
39
14/6
23
20/16 16/12
35
they thought that attacks were more or less frequent over the past 5-10 years. Nineteen patients with a malignancy or Iymphoma had noted an increased frequency of attacks since diagnosis of their underlying disease and all related the increase to treatment.
628
Warwick L.Morison
Herpes zoster The incidence of this infection is given in Table 4. Herpes zoster is more common in patients with Hodgkin's disease, malignant lymphoma and C.L.L. as compared to the other groups and controls. The increased incidence is mainly accounted for by attacks occurring after the onset of the disease. It is interesting that five patients with lymphomas gave a history of two separate episodes of zoster infection. TABLE 4. Incidence of herpes zoster infection
Incidence (%)
Controls Multiple myeloma Hodgkin's disease Malignant lymphoma C.L.L. Systemic malignancy B.C.C.
Cases occurring after onset of disease (7o)
II
m
38 =26 2f: 13 15
8 68 46 64 30 8
DISCUSSION
Viral warts This survey shows a greatly increased incidence of warts in patients with Hodgkin's disease and a lesser but still marked increase in patients with C.L.L. and malignant lymphoma. As explained earlier, this group are at least to some degree deficient in cell-mediated immunity. In contrast, patients with multiple myeloma do not show an increased incidence of warts and these patients are, if anything, deficient in humoral antibody responses. The increase of warts in the Hodgkin's-lymphomaleukaemia group is not just due to treatment because the incidence had risen before any treatment had been given and, furthermore, myeloma patients also receive chemotherapy and radiotherapy. The results of this survey suggest that patients with cell-mediated immune deficiency are prone to wart infection while those with humoral immune deficiency are not. Furthermore, once a patient with such a deficiency develops warts they are unlikely to resolve spontaneously or to show a satisfactory response to conventional therapy. It is therefore suggested that cell-mediated immune responses are an important factor both in preventing warts and in bringing about their successful resolution. In addition it is suggested that humoral antibodies are not important in preventing wart infection. Only one previous survey of warts in immune deficient patients could be found in the literature (Spencer & Anderson, 1970). They found that 42% of fifty-five renal transplant patients developed warts within a year of transplantation. Prednisone and azathioprine, used for immunosuppression in their patients, particularly depresses cell-mediated immunity and therefore that study would appear to support the present results. Patients with systemic and cutaneous malignancy of the carcinoma-sarcoma variety do not appear to be different from the control group so far as the incidence of warts is concerned. Therefore this survey does not support the suggestion of a reduced incidence of warts in patients with carcinoma (Hoon & Ansfield, 1964).
Dermatoses in secondary immune deficiency states
629
Recurrent herpes simplex
Two interesting findings emerge from this part of the study. Firstly, the low incidence of herpes simplex found in patients with myeloma and systemic malignancy. A recent survey (Ross & Tyrrell, 1974) among patients with carcinoma of the lung found a very similar result, 21% of patients having a history of herpes simplex infection as against 42% of the controls. The authors suggested that recurrent herpes simplex raises the level of immunity to malignancy by stimulating immunological surveillance. However if this was the case the Hodgkin's-lymphoma-leukaemia group, which are also malignancies, might be expected to show a reduced incidence, but in the present study they differ little from the controls. The second interesting finding is that there is no indication from this survey that immunological factors are important in determining the incidence of recurrent herpes simplex. The role of immune function in this infection in humans is at present poorly defined. That humoral antibodies alone play no significant part has been established (Douglas & Couch, 1970) but the importance of cell-mediated immunity is debatable. Severe herpes simplex has been reported in renal transplant patients (Montgomerie et al., 1969) but the four patients discussed also had cytomegalovirus in their lesions, a virus now known to cause severe infections in immuno-suppressed patients (Lopez et al., 1973). The Wiskott-Aldrich syndrome is another disease reported (Cooper et al., 1968) to show an increased incidence and severity of herpes simplex infection. However patients with this syndrome also have eczema, which can of course lead to widespread herpes simplex infection in the absence of any demonstrable immune defect. Two surveys (Spencer & Anderson, 1970; Rifkind, 1964) as opposed to case reports, have found that the incidence and severity of recurrent herpes simplex is not increased in immuno-suppressed renal transplant patients. An increase in frequency of attacks was noted in all disease groups by at least some patients in the present study and was usually attributed to treatment. This increase is probably not due to an immune disturbance, but instead, could arise from non-specific factors such as debility, operating in a similar manner to coryza and sunlight, both well-known precipitants of herpes simplex infection. Herpes zoster
The association of herpes zoster and malignancy has long been recognized and has been analysed in many different ways, but this appears to be the first survey to look at the incidence from the viewpoint of the immune state of the patients. There is a considerable increase in the incidence of zoster in the Hodgkin's-lymphoma-leukaemia groups and this increase is mainly accounted for by cases occurring after the onset of the disease. Therefore treatment may have an infiuence here. However myeloma patients also receive similar immuno-suppressive treatment and they do not show this increase after the onset of the disease. In fact, even though the myeloma patients are in an older age group than the controls, they show little increase in the incidence of zoster infection. As with warts, the present survey showed that the most marked increase in the incidence of zoster occurs in patients with some degree of cell-mediated immune deficiency while those having only a humoral immune deficiency show little increase. It is therefore possible that the prevention of herpes zoster is a function of cell-mediated immune responses. , CONCLUSIONS
(i) The incidence of viral warts is increased in patients with: Hodgkin's disease Malignant lymphoma Chronic lymphatic leukaemia
630
Warwick L.Morison
(2) The incidence of herpes zoster is increased in patients with: Hodgkin's disease Malignant lymphoma Chronic lymphatic letikaemia (3) This study suggests that: (a) Cell-mediated immunity may be important in both the prevention and resolution of infections due to wart virus. (b) Cell-mediated immtinity may be important in preventing infections due to varicella-zoster virus. (c) Immunological factors are not important in preventing recurrent herpes simplex infections. ACKNOWLEDGMENTS
The Author wishes to thank the people who made this survey possible by their help and co-operation, Drs T.J.McElwain and M.J.Peckham of the Royal Marsden Hospital, Sutton; Dr E.Wiltshaw of the Royal Marsden Hospital, Fultham; Professor G.H.Fairley of St Bartholomew's Hospital; Professor G.Wetherley-Mein and Dr C.D.Collins of St Thomas' Hospital; and all the consultants at St Helier Hospital. St John's Hospital Medical Illustration Department kindly provided the illustrations. This work was made possible by a grant from the S.W. Metropolitan Regional Hospital Board. REFERENCES COOPER, M.D., CHASE, H.P., LOWMAN, J.T., KRIVIT, W . & GOOD, R . A . (1968) Wiskott-Aldrich Syndrome.
American Journal of Medicine, 44, 499. DOUGLAS, R . G . & COUCH, R . B . (1970) A prospective study of chronic herpes infection and recurrent herpes labialis in humans. Journal of Immunology, 104, 289. HOON, J.R. & ANSFIELD, F.J. (1964) Interference between verruca vulgaris and malignant growths in humans. Annals of the New York Academy of Science, 118, 453. LOPEZ, C , SIMMONS, R.L., MAUER, M . , PARK, B., NATARIAN, J . S . & GOOD, R.A. (1973) Role of virus infections
in immuno-suppressed renal transplant patients. Transplantation Proceedings, 5, 803. MoNTGOMERiE, J.Z., BECROFT, D.M.O., CROXSON, M . C , DOAK, P . B . & NORTH, J . D . K . (1969) Herpes simplex
virus infection after renal transplantation. Lancet, ii, 867. RiFKiND, D. (1964) Infectious diseases associated with renal transplantation. In: Experiences in Renal Transplantation (Ed. by T.E.Starzl), p. 213. Saunders, Philadelphia and London. Ross, C.A.C. & TYRRELL, W . F . (1974) Possible prevention of bronchial carcinoma by recurrent herpes simplex. Lancet, i, 871. SPENCER, E . S . & ANDERSON, H . K . (1970) Clinically evident, non-terminal infections with herpes virus and wart virus in immuno-suppressed renal allograft recipients. British Medical Journal, 3, 251.
