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Quality of life improvement in a patient with severe atopic dermatitis treated with photopheresis
780 Brief communications
Journal of the American Academy of Dermatology May 1999
Quality of life improvement in a patient with severe atopic dermatitis treated with photopheresis Geeta Mohla, BS, Nancy Horvath, and Seth Stevens, MD Cleveland, Ohio Atopic dermatitis is a common skin disease characterized by severely pruritic eczematous patches, papular and lichenified plaques, excoriations, cracks, and erosions. Photopheresis has been shown to ameliorate the signs and symptoms of atopic dermatitis in some patients. We describe successful results with photopheresis for refractory disease in a patient who chronicled his quality of life weekly for more than 15 years before and during extracorporeal photochemotherapy. (J Am Acad Dermatol 1999;40:780-2.)
Atopic dermatitis (AD) is a common disease, with an incidence of 10% in infants.1 AD is characterized by severely pruritic papular and lichenified plaques, excoriations, cracks, and erosions and is a cause of chronic and recurrent physical and psychologic disability. Although AD has been the subject of much investigation and has served as a model for understanding human immune responses, no cure has been found. Furthermore, in some patients, therapy for AD remains unsatisfactory. For many patients, immunosuppression with systemic corticosteroids, azathioprine, methotrexate, cyclosporine, or PUVA are the only means of preventing severe disability; however, these therapies carry the risk of significant adverse effects. Indeed, for some patients, even the use of these potentially risky therapies is insufficient to obtain meaningful relief. Photopheresis (extracorporeal photochemotherapy, ECP) was initially developed for the treatment of cutaneous T-cell lymphoma.2 Subsequently, other diseases such as graftversus-host disease, scleroderma, solid organ transplant rejection, lupus erythematosus, and pemphigus vulgaris have been successfully treated with ECP.3 ECP involves ingesting photoactivatable methoxsalen by the patient, exposing the patient’s mononuclear leuko-
cytes (separated from the blood) to extracorporeal UVA irradiation, and reinfusing the cells into the patient. This procedure is typically performed over 2 consecutive days. Although the precise mechanism of action of ECP is unclear, such treatment appears to be immunomodulatory, perhaps through induction of apoptosis of pathogenic T cells.3,4 Previous reports of ECP for AD demonstrate amelioration of skin signs and symptoms in 6 patients treated.4,5 ECP has also been found to improve laboratory correlates of active AD: hyperimmunoglobulinemia E and elevated eosinophilic cationic protein.4,5 These studies vary in the time interval between ECP courses. Whereas Prinz, Nachbar, and Plewig4 report that once-monthly treatment is effective, Richter et al5 suggest that ECP every 2 weeks may be necessary. Nevertheless, no accepted protocol has been designed for the ideal period between courses. We describe successful therapy for refractory AD in which the patient chronicled his quality of life weekly for more than 15 years before and during ECP therapy. The patient devised his own qualityof-life tool as depicted in Table I. We used a modified Atopic Dermatitis Area and Severity Index6 to quantitate AD status, as in the equation: Score = Amild + 2(Amoderate) + 4(Asevere)
From the Photopheresis Service, University Hospitals of Cleveland, Ireland Cancer Center, Case Western Reserve University. Reprint requests: Seth Stevens, MD, Department of Dermatology, University Hospitals of Cleveland, 11100 Euclid Ave, Cleveland, OH 44106-5028. Copyright © 1999 by the American Academy of Dermatology, Inc. 0190-9622/99/$8.00 + 0 16/54/97587
where Amild is the percentage of total body surface area (% TBSA) involved with mild disease, Amoderate is the % TBSA involved with moderate disease, and Asevere is the % TBSA involved with severe disease.
Journal of the American Academy of Dermatology Volume 40, Number 5, Part 1
Brief communications 781
Fig 1. Patient-derived quality of life (QOL) score while on various therapies for AD. –, Duration of therapy indicated; ↑, ECP; *, hospitalization; AZA, azathioprine; CSA, cyclosporine; IFNg, interferon gamma; MTX, methotrexate; UV, ultraviolet light.
CASE REPORT This patient is a 49-year-old man with a life-long history of AD associated with asthma and allergic rhinitis, with severe manifestations of his disease for the past 20 years. From 1984 to mid-1993, systemic corticosteroids were the mainstay of his treatment; however, this regimen was eventually insufficient to adequately suppress the disease process. Several therapies were then tried in conjunction with topical steroids: UVB, interferon gamma, azathioprine, methotrexate, combined UVA/UVB, and cyclosporine. These therapies were ineffective in controlling disease activity at doses believed to be safe for the patient, and he was hospitalized twice during this time. Photopheresis was begun in conjunction with twice-daily topical steroids in February 1997, with courses every 2 weeks for the first 2 months, then every 4 weeks for the next 2 months. The patient noticed improvement of his disease-specific quality of life (QOL) by the end of the fifth cycle (Fig 1). His skin score also began to improve at about the same time (Fig 2). ECP was discontinued after his fourth month of treatment (6 courses), and the AD flared within 1 month. During the second month without ECP, the patient was back to his baseline disease activity (Figs 1 and 2). ECP was then reinstituted every 4 weeks for the next 4 months with significant improve-
Table I. Patient-devised quality of life assessment Score
1 2 3 4 5 6 7 8 9
Status
Optimal, soft skin, no blemishes, no inflammation Feeling very well, few blemishes, little inflammation Feeling well, some blemishes, some inflammation Coping, inflammation Coping, scratching, inflammation Not well Not well Hospitalization Hospitalization
ment in his condition. The patient also did well with a second hiatus of 3 months and was restarted on ECP every 6 weeks. ECP was stopped after a total of 14 treatments. The patient is essentially clear of AD lesions, although he has marked striae and cutaneous atrophy from long-term topical steroid use. Our patient noted no adverse effects while receiving ECP.
782 Brief communications
Fig 2. Clinical status of AD monitored with modified ADASI. +, ECP treatment and clinical assessment; s = clinical assessment only after discontinuation of ECP. Analysis by unpaired t test showed that for the 171 weeks before initiation of ECP, his disease impact (QOL) score was 4.6 ± 0.9; for the 62 weeks since beginning ECP, his score was 3.3 ± 1.4 (P < .0001; unpaired, two-tailed t test). If we exclude the flare, which occurred during the 13 weeks he missed ECP between the seventh and eighth courses, his score during ECP shows improvement to 2.8 ± 1.1 (P < .0001). DISCUSSION
Our results support the European reports on 6 patients and show, in a US center, that photopheresis can be highly effective therapy for recalcitrant AD. Furthermore, these results extend the documented clinical and laboratory improvements to include important quality-of-life issues. We recognize that this instrument devised by our patient many years before coming to our center has not been formally validated. However, this scale has the advantage of being derived by the patient and therefore captures his sense of well-being in his own words, with definitions that are consistently and completely understood by the patient. Clinically, our patient did extremely well on ECP, with complete clearing by clinical and quality-oflife assessments by the patient. ECP consistently surpassed previous aggressive outpatient or inpatient therapies. Our patient reported no adverse experiences. Those of Richter et al5 likewise reported no “serious side effect.” One patient of Prinz, Nachbar,
Journal of the American Academy of Dermatology May 1999
and Plewig4 did report mild nausea after psoralen ingestion. Although no patient with AD reported to date has experienced any significant adverse event, the risks of ECP, as determined in other patient populations, include infection as well as pulmonary and peripheral edema. Richter et al5 suggest that the efficacy of ECP for AD relies on the time interval between treatments and indicate that every-other-week ECP monotherapy may be most effective. Our patient did show improvement during every-other-week therapy; however, while on monthly ECP and even during extended treatment hiatuses, he continued to maintain marked improvement. No specific guidelines for timing between ECP courses can be confirmed as of yet; nonetheless, it is clear that some patients may respond well to less frequent ECP. Richter et al5 also note two long-term remissions after discontinuing ECP after 10 courses. Our patient had a relapse during the first treatment hiatus, but quickly responded to reinstitution of ECP. This response was maintained after the second hiatus, which occurred after the tenth course of treatment, and he remains essentially clear of the signs of AD 2 months after discontinuing therapy. Thus in some patients a total cumulative dose of ECP, independent of interval between courses including short treatment interruptions, may be necessary to induce a remission. We conclude that for some patients with difficult-to-manage AD, ECP is a safe and viable treatment option with few adverse effects beyond cost. REFERENCES 1. Larsen FS, Holm NV, Henningsen K. Atopic dermatitis: a genetic-epidemiologic study in a population-based twin sample. J Am Acad Dermatol 1986;15:487-94. 2. Edelson R, Berger C, Gasparo F, Jegasothy B, Heald P, Wintroub F, et al. Treatment of cutaneous T-cell lymphoma by extracorporeal photochemotherapy: preliminary results. N Engl J Med 1987;316:297-303. 3. Edelson RL, Perez M, Heald P, Berger C. Extracorporeal photochemotherapy. Biol Ther Cancer Updates 1994;4: 1-12. 4. Prinz B, Nachbar F, Plewig G. Treatment of severe atopic dermatitis with extracorporeal photopheresis. Arch Dermatol Res 1994;287:48-52. 5. Richter HI, Billmann-Eberwein C, Grewe K, Stege IL, Berneburg K, Ruzicka T, et al. Successful monotherapy of severe and intractable atopic dermatitis by photopheresis. J Am Acad Dermatol 1998;38:585-8. 6. Bahmer FA, Schafer J, Schubert HJ. Quantification of the extent and the severity of atopic dermatitis: the ADASI score [letter]. Arch Dermatol 1991;127:1239-40.
Journal of the American Academy of Dermatology May 1999
Quality of life improvement in a patient with severe atopic dermatitis treated with photopheresis Geeta Mohla, BS, Nancy Horvath, and Seth Stevens, MD Cleveland, Ohio Atopic dermatitis is a common skin disease characterized by severely pruritic eczematous patches, papular and lichenified plaques, excoriations, cracks, and erosions. Photopheresis has been shown to ameliorate the signs and symptoms of atopic dermatitis in some patients. We describe successful results with photopheresis for refractory disease in a patient who chronicled his quality of life weekly for more than 15 years before and during extracorporeal photochemotherapy. (J Am Acad Dermatol 1999;40:780-2.)
Atopic dermatitis (AD) is a common disease, with an incidence of 10% in infants.1 AD is characterized by severely pruritic papular and lichenified plaques, excoriations, cracks, and erosions and is a cause of chronic and recurrent physical and psychologic disability. Although AD has been the subject of much investigation and has served as a model for understanding human immune responses, no cure has been found. Furthermore, in some patients, therapy for AD remains unsatisfactory. For many patients, immunosuppression with systemic corticosteroids, azathioprine, methotrexate, cyclosporine, or PUVA are the only means of preventing severe disability; however, these therapies carry the risk of significant adverse effects. Indeed, for some patients, even the use of these potentially risky therapies is insufficient to obtain meaningful relief. Photopheresis (extracorporeal photochemotherapy, ECP) was initially developed for the treatment of cutaneous T-cell lymphoma.2 Subsequently, other diseases such as graftversus-host disease, scleroderma, solid organ transplant rejection, lupus erythematosus, and pemphigus vulgaris have been successfully treated with ECP.3 ECP involves ingesting photoactivatable methoxsalen by the patient, exposing the patient’s mononuclear leuko-
cytes (separated from the blood) to extracorporeal UVA irradiation, and reinfusing the cells into the patient. This procedure is typically performed over 2 consecutive days. Although the precise mechanism of action of ECP is unclear, such treatment appears to be immunomodulatory, perhaps through induction of apoptosis of pathogenic T cells.3,4 Previous reports of ECP for AD demonstrate amelioration of skin signs and symptoms in 6 patients treated.4,5 ECP has also been found to improve laboratory correlates of active AD: hyperimmunoglobulinemia E and elevated eosinophilic cationic protein.4,5 These studies vary in the time interval between ECP courses. Whereas Prinz, Nachbar, and Plewig4 report that once-monthly treatment is effective, Richter et al5 suggest that ECP every 2 weeks may be necessary. Nevertheless, no accepted protocol has been designed for the ideal period between courses. We describe successful therapy for refractory AD in which the patient chronicled his quality of life weekly for more than 15 years before and during ECP therapy. The patient devised his own qualityof-life tool as depicted in Table I. We used a modified Atopic Dermatitis Area and Severity Index6 to quantitate AD status, as in the equation: Score = Amild + 2(Amoderate) + 4(Asevere)
From the Photopheresis Service, University Hospitals of Cleveland, Ireland Cancer Center, Case Western Reserve University. Reprint requests: Seth Stevens, MD, Department of Dermatology, University Hospitals of Cleveland, 11100 Euclid Ave, Cleveland, OH 44106-5028. Copyright © 1999 by the American Academy of Dermatology, Inc. 0190-9622/99/$8.00 + 0 16/54/97587
where Amild is the percentage of total body surface area (% TBSA) involved with mild disease, Amoderate is the % TBSA involved with moderate disease, and Asevere is the % TBSA involved with severe disease.
Journal of the American Academy of Dermatology Volume 40, Number 5, Part 1
Brief communications 781
Fig 1. Patient-derived quality of life (QOL) score while on various therapies for AD. –, Duration of therapy indicated; ↑, ECP; *, hospitalization; AZA, azathioprine; CSA, cyclosporine; IFNg, interferon gamma; MTX, methotrexate; UV, ultraviolet light.
CASE REPORT This patient is a 49-year-old man with a life-long history of AD associated with asthma and allergic rhinitis, with severe manifestations of his disease for the past 20 years. From 1984 to mid-1993, systemic corticosteroids were the mainstay of his treatment; however, this regimen was eventually insufficient to adequately suppress the disease process. Several therapies were then tried in conjunction with topical steroids: UVB, interferon gamma, azathioprine, methotrexate, combined UVA/UVB, and cyclosporine. These therapies were ineffective in controlling disease activity at doses believed to be safe for the patient, and he was hospitalized twice during this time. Photopheresis was begun in conjunction with twice-daily topical steroids in February 1997, with courses every 2 weeks for the first 2 months, then every 4 weeks for the next 2 months. The patient noticed improvement of his disease-specific quality of life (QOL) by the end of the fifth cycle (Fig 1). His skin score also began to improve at about the same time (Fig 2). ECP was discontinued after his fourth month of treatment (6 courses), and the AD flared within 1 month. During the second month without ECP, the patient was back to his baseline disease activity (Figs 1 and 2). ECP was then reinstituted every 4 weeks for the next 4 months with significant improve-
Table I. Patient-devised quality of life assessment Score
1 2 3 4 5 6 7 8 9
Status
Optimal, soft skin, no blemishes, no inflammation Feeling very well, few blemishes, little inflammation Feeling well, some blemishes, some inflammation Coping, inflammation Coping, scratching, inflammation Not well Not well Hospitalization Hospitalization
ment in his condition. The patient also did well with a second hiatus of 3 months and was restarted on ECP every 6 weeks. ECP was stopped after a total of 14 treatments. The patient is essentially clear of AD lesions, although he has marked striae and cutaneous atrophy from long-term topical steroid use. Our patient noted no adverse effects while receiving ECP.
782 Brief communications
Fig 2. Clinical status of AD monitored with modified ADASI. +, ECP treatment and clinical assessment; s = clinical assessment only after discontinuation of ECP. Analysis by unpaired t test showed that for the 171 weeks before initiation of ECP, his disease impact (QOL) score was 4.6 ± 0.9; for the 62 weeks since beginning ECP, his score was 3.3 ± 1.4 (P < .0001; unpaired, two-tailed t test). If we exclude the flare, which occurred during the 13 weeks he missed ECP between the seventh and eighth courses, his score during ECP shows improvement to 2.8 ± 1.1 (P < .0001). DISCUSSION
Our results support the European reports on 6 patients and show, in a US center, that photopheresis can be highly effective therapy for recalcitrant AD. Furthermore, these results extend the documented clinical and laboratory improvements to include important quality-of-life issues. We recognize that this instrument devised by our patient many years before coming to our center has not been formally validated. However, this scale has the advantage of being derived by the patient and therefore captures his sense of well-being in his own words, with definitions that are consistently and completely understood by the patient. Clinically, our patient did extremely well on ECP, with complete clearing by clinical and quality-oflife assessments by the patient. ECP consistently surpassed previous aggressive outpatient or inpatient therapies. Our patient reported no adverse experiences. Those of Richter et al5 likewise reported no “serious side effect.” One patient of Prinz, Nachbar,
Journal of the American Academy of Dermatology May 1999
and Plewig4 did report mild nausea after psoralen ingestion. Although no patient with AD reported to date has experienced any significant adverse event, the risks of ECP, as determined in other patient populations, include infection as well as pulmonary and peripheral edema. Richter et al5 suggest that the efficacy of ECP for AD relies on the time interval between treatments and indicate that every-other-week ECP monotherapy may be most effective. Our patient did show improvement during every-other-week therapy; however, while on monthly ECP and even during extended treatment hiatuses, he continued to maintain marked improvement. No specific guidelines for timing between ECP courses can be confirmed as of yet; nonetheless, it is clear that some patients may respond well to less frequent ECP. Richter et al5 also note two long-term remissions after discontinuing ECP after 10 courses. Our patient had a relapse during the first treatment hiatus, but quickly responded to reinstitution of ECP. This response was maintained after the second hiatus, which occurred after the tenth course of treatment, and he remains essentially clear of the signs of AD 2 months after discontinuing therapy. Thus in some patients a total cumulative dose of ECP, independent of interval between courses including short treatment interruptions, may be necessary to induce a remission. We conclude that for some patients with difficult-to-manage AD, ECP is a safe and viable treatment option with few adverse effects beyond cost. REFERENCES 1. Larsen FS, Holm NV, Henningsen K. Atopic dermatitis: a genetic-epidemiologic study in a population-based twin sample. J Am Acad Dermatol 1986;15:487-94. 2. Edelson R, Berger C, Gasparo F, Jegasothy B, Heald P, Wintroub F, et al. Treatment of cutaneous T-cell lymphoma by extracorporeal photochemotherapy: preliminary results. N Engl J Med 1987;316:297-303. 3. Edelson RL, Perez M, Heald P, Berger C. Extracorporeal photochemotherapy. Biol Ther Cancer Updates 1994;4: 1-12. 4. Prinz B, Nachbar F, Plewig G. Treatment of severe atopic dermatitis with extracorporeal photopheresis. Arch Dermatol Res 1994;287:48-52. 5. Richter HI, Billmann-Eberwein C, Grewe K, Stege IL, Berneburg K, Ruzicka T, et al. Successful monotherapy of severe and intractable atopic dermatitis by photopheresis. J Am Acad Dermatol 1998;38:585-8. 6. Bahmer FA, Schafer J, Schubert HJ. Quantification of the extent and the severity of atopic dermatitis: the ADASI score [letter]. Arch Dermatol 1991;127:1239-40.