ARTICLE
Introduction
Numerous studies have shown a beneficial effect of ultraviolet radiation
for the treatment of chronic inflammatory or lymphoproliferative skin
diseases. Advances in our understanding of the pathogenesis of these skin
diseases have prompted the development of new phototherapeutic strategies
such as long-wave UVA (UVA1), narrowband UVB (TL-01), bath water delivery
of 8-MOP followed by UVA (bath-PUVA) or the combination of salt water
brine baths and UVA/B, and extracorporeal photopheresis (ECP). Here we
review these phototherapeutic approaches and discuss their indications
and potential risks and benefits. In recent years great progress was also
made in the development of photodynamic therapy (PDT) as an alternative
therapeutic option for superficial skin tumours or psoriasis [1, 2]. However,
PDT will not be the focus in this review.
UVA1 phototherapy
UVA1 phototherapy utilizes long wave UVA radiation (340-400 nm) while
filtering out the erythematogenic UVA and UVB wavelengths (290-340 nm).
It has been shown to be very effective in the treatment of several inflammatory
skin diseases such as atopic dermatitis, localized scleroderma, urticaria
pigmentosa, disseminated granuloma annulare and in some cases in systemic
sclerosis, lichen sclerosus et atrophicans, graft-versus-host disease
(GvHD), cutaneous T cell lymphoma and psoriasis in HIV-infected individuals.
Different dosage regimen have been proposed for UVA1 phototherapy: low
dose (10-20 J/cm2 per single dose), medium dose (50-60 J/cm2
per single dose) or high dose (130 J/cm2 per single dose) UVA1
therapy. The therapeutic efficacy of high dose UVA1 irradiation in the
treatment of patients with acutely exacerbated atopic dermatitis was first
reported in 1991 and was confirmed in several subsequent studies [3-5].
It can be used as a monotherapy for a limited period of time (10-15 exposures,
max. twice yearly) and as such seems to be an alternative to long-term
glucocorticosteroid use [3, 4]. However, some patients with atopic dermatitis
do not respond well to high dose UVA1. These Non-Responders are characterized
by severe atopy and by concomitant bacterial or fungal superinfections
and might benefit from a combination of high dose UVA1 with antibiotic
or antimycotic treatment [5]. Of note, subsequent studies have demonstrated
intermediate dose UVA1-phototherapy also to be effective in the treatment
of moderate severity AD [6, 7]. In a recent pilot study, we demonstrated
a statistically significant reduction of the SCORAD after 15 treatments
with high or medium dose UVA1 therapy compared to low dose therapy [8].
Histopathological analysis of UVA1 irradiated skin revealed a reduction
of mast cells and an induction of collagenase-I-activity. Based on these
results, UVA1 was successfully used in the treatment of urticaria pigmentosa
(130 J/cm2 x 10) [9] and, in different dosage regimen, in localized
scleroderma (130 J/cm2 x 30 or 20 J/cm2 x 24 respectively)
[10, 11] and in scleroderma in systemic sclerosis [12]. Furthermore, improvement
of skin lesions in patients with disseminated granuloma annulare by high
dose UVA1 phototherapy (130 J/cm2 x 15) has recently been reported
[13]. Despite all the benefits of UVA1, little data exist on potential
long-term safety risks such as photodamage and skin carcinogenesis in
humans, particularly of the high dose regimen. Therefore, we recommend
that patients should be treated with high dose UVA1 phototherapy no more
than twice yearly for up to 15 irradiations per therapy cycle, they should
be > 18 years, and they should be monitored at least once a year for
the potential occurrence of photodamage or skin cancer.
Narrowband (TL-01) UVB
The narrowband UVB lamp with an emission spectrum peaking at 311-313
nm (Philips TL-01/100 W) was developed as an alternative to broadband
UVB (290-320 nm) for the phototherapy of psoriasis to reduce erythemogenicity
and the risk of skin carcinogenesis. Several studies comparing it with
conventional broad-spectrum UVB phototherapy in patients with psoriasis
reported greater therapeutic efficacy for narrowband UVB phototherapy
[14, 15]. A combination of narrowband UVB with dithranol [14] or with
oral retinoids [16] resulted in even faster clearance of the psoriatic
lesions. In one study, narrowband UVB appeared to be almost as effective
as systemic PUVA photochemotherapy [17]. Narrowband UVB used in combination
with systemic 8-methoxypsoralen treatment (PUVB) proved as good as systemic
PUVA [18]. When combined with topical (bath) 8-MOP delivery, narrowband
UVB phototherapy was even superior to broadband UVA irradiation [18].
Narrowband UVB phototherapy was also used in the management of atopic
eczema, resulting in the amelioration of pruritus, restoration of a normal
sleep pattern and a reduction of topical steroid use [19]. In patients
with photosensitivity diseases such as polymorphic light eruption, TL-01
produces a "hardening" photoprotective effect [20]. Long-term side effects
of narrowband UVB phototherapy, such as potential skin carcinogenesis,
seem to be at least equal to and possibly less frequent than would be
expected from broadband UVB sources [21, 22].
Balneophototherapy
Balneophototherapy combines bath water delivery of water soluble photosensitizers
or antiinflammatory agents for example 8-methoxypsoralen (8-MOP) or different
salt solutions with a subsequent UVB- or UVA-irradiation [reviewed in
23]. In recent years, the combination of brine baths or 8-MOP-baths with
UVB- or UVA-phototherapy using artificial light sources has been used
increasingly in the treatment of psoriasis and atopic dermatitis [24,
25]. Administration of 8-MOP in a dilute bath water solution seems to
be an effective alternative to its widely used systemic application, avoiding
side effects such as nausea, vomiting, elevation of liver transaminases
or even photodamage to the eyes and furthermore reduces cumulative UVA
doses [26]. Furthermore, bath water delivery results in a uniform cutaneous
absorption and a homogeneous skin distribution of 8-MOP. The optimal time
for UVA irradiation is immediately after the 8-MOP bath. In contrast to
systemic PUVA therapy, photosensitivity is lost within two hours after
8-MOP bath, which is a substantial advantage for patients, avoiding the
need for prolonged UV protection of the skin and eyes [27, 28].
PUVA bath therapy proved to be effective in psoriasis, mycosis fungoides,
lichen planus, localized scleroderma, urticaria pigmentosa and chronic
palmoplantar eczema [23, 29]. PUVA bath therapy can also be combined with
oral acitretin for the efficient treatment of severe psoriasis [30]. Several
case reports documented a beneficial effect of bath PUVA in the treatment
of prurigo, vitiligo or severe atopic dermatitis [reviewed in 23].
Investigation of the effectiveness of salt water baths containing either
15% synthetic Dead Sea salt called "Psorisal" or 3% NaCl solution in 40
patients with psoriasis and AD led to significantly better results in
80% of the patients of the "Psorisal" treatment group [31]. Balneophototherapy
of atopic dermatitis with a combination of 3-5% salt water brine baths
and subsequent UVA/B irradiation led to a SCORAD reduction from 70 to
37 after 20 treatments in 28 patients with atopic dermatitis [32]. The
treatment of psoriasis with a combination of 15% salt water brine baths
and subsequent UVB irradiation led to a PASI reduction about 83% from
16.2 to 2.75 after 21 treatments in 4,024 patients with psoriasis [33].
Possible modes of action of salt water baths are the elution of chemotactic
and proinflammatory mediators, and immunomodulatory skin effects [34,
35]. Other mechanisms, such as increased photosensitivity may contribute
to the efficacy of salt baths followed by UV radiation [36].
Extracorporeal photopheresis
(ECP)
Extracorporeal photopheresis (ECP) was first introduced 1987 by Edelson
et al. as a therapeutic regimen for Sezary's syndrome [37]. However,
in recent years, it has been used successfully for other indications such
as chronic graft-versus-host disease (GvHD), systemic scleroderma,
pemphigus vulgaris, rheumatoid arthritis, lupus erythematodes and even
severe atopic dermatitis [38-44]. ECP is a discontinuous leukapheresis
procedure that combines administration of 8-methoxypsoralen (8-MOP) with
extracorporeal UVA irradiation to a fraction of the peripheral blood leukocytes.
Thus it targets the effects of photochemotherapy directly to circulating,
pathogenic leukocytes [40]. 8-MOP photosensitization of leukocytes can
be achieved either by systemic administration, where treatment efficacy
depends essentially on sufficient 8-MOP plasma levels, or by direct administration
of 8-MOP to the leucocyte fraction [39].
To date, ECP is considered as first-line treatment for CTCL-stages III
and IV (TNM- classification) and can also be used in combination with
interferon alfa or methotrexate in cases of treatment failure of an ECP
monotherapy [44]. In patients with GvHD, ECP led to an omission of immunosuppressive
drugs after 15 treatment cycles within 12 months because of noticeable
improvement in cutaneous changes, liver function parameters and general
condition [38]. Moreover, ECP was reported to be effective in the treatment
of certain autoimmune diseases such as systemic scleroderma or pemphigus
[42, 43]. ECP has also been used successfully in the treatment of severe
atopic dermatitis. In the study of Prinz et al., ECP resulted in
a marked clinical improvement of the skin lesions of 4 patients after
5 cycles (4-week-intervals) of ECP in average and was reflected by a marked
reduction in IgE serum levels. Clinical remission was stable under maintenance
therapy with prolonged intervals (6-week-intervals) between photopheresis
sessions [41].
Outlook
In the past, research in photodermatology has led to refinements of
phototherapy modalities such as UVA1, narrowband (TL-01) UVB, balneophototherapy
and extracorporeal photopheresis. These new and promising approaches in
the management of chronic inflammatory or lymphoproliferative skin diseases
are effective, but a standardization of dosage regimen and quality control
is necessary to avoid potential long-term safety risks such as photodamage
and skin carcinogenesis.
Article accepted on 27/10/00
REFERENCES
1. Boehncke WH, Sterry W, Kaufmann R. Treatment of psoriasis by
topical photodynamic therapy with polychromatic light. Lancet 1994;
343: 801.
2. Fijan S, Hönigsmann H, Ortel B. Photodynamic therapy
of epithelial skin tumours using delta-aminolevulinic acid and desferrioxamine.
Br J Dermatol 1995; 133: 282-8.
3. Krutmann J, Czech W, Diepgen T, et al. High-dose UVA1
therapy in the treatment of patients with atopic dermatitis. J Am Acad
Dermatol 1992; 26: 225-30.
4. Krutmann J, Diepgen T, Luger TA, et al. High-dose UVA1
therapy for atopic dermatitis: results of a multicenter trial. J Am
Acad Dermatol 1998; 38: 589-93.
5. Schempp CM, Effinger T, Czech W, et al. Characterization
of non-responders in high-dose UVA1 therapy of patients with atopic dermatitis.
Hautarzt 1997; 48: 94-9.
6. Meffert H, Sönnichsen N, Herzog M, et al. UVA-1-Kaltlichttherapie
des akut exazerbierten, schweren atopischen Ekzems. Dermatol Monatsschr
1992; 178: 291-6.
7. Kowalzick L, Kleinheinz A, Weichenthal M, et al. Low
dose versus medium dose UV-A1 treatment in severe atopic eczema.
Acta Derm Venereol 1995; 75: 43-5.
8. Dittmar HC, Pflieger D, Schöpf E, et al. UVA1-Phototherapie:
Pilotstudie zur Dosisfindung bei der akut exazerbierten Atopischen Dermatitis.
Hautarzt 2000 (in press).
9. Stege S, Schöpf E, Ruzicka T, et al. High-dose
UVA1 for urticaria pigmentosa. Lancet 1996; 347: 64.
10. Stege S, Berneburg M, Humke S, et al. High-dose UVA1
radiation therapy for localized scleroderma. J Am Acad Dermatol
1997; 36: 938.
11. Kerscher M, Dirschka T, Volkenandt M. Treatment of localized
scleroderma by UVA1 phototherapy. Lancet 1995; 346: 1166.
12. Morita A, et al. Ultraviolet A1 (340-400 nm) phototherapy
for scleroderma in systemic sclerosis. J Am Acad Dermatol 2000;
43: 670-4.
13. Muchenberger S, Schëpf E, Simon JC. UVA1-phototherapy
for generalized granuloma anulare. Arch Dermatol 1997; 133: 1605.
14. Storbeck K, Hölzle E, Lehmann P, et al. Die Wirksamkeit
eines neuen Schmalspektrum-UV-B-Strahlers (Philips TL 01 100W, 311 nm)
im Vergleich zur konventionellen UV-B-Phototherapie der Psoriasis. Z
Hautkr 1991; 66: 708-12.
15. Van Weelden H, Baart de la Faille H, Young E, et al.
A new development in UVB phototherapy of psoriasis. Br J Dermatol
1988; 119: 11-9.
16. Green C, Lakshmipathi T, Johnson BE, et al. A comparison
of the efficiency and relapse rates of narrowband UVB (TL-01) monotherapy
vs etretinate-PUVA (re-PUVA) in the treatment of psoriasis patients.
Br J Dermatol 1992; 127: 5-9.
17. Van Weelden H, Baart de la Faille H, Young E, et al.
Comparison of Narrow-band UV-B phototherapy and PUVA photochemotherapy
in the treatment of psoriasis. Acta Derm Venereol (Stockh) 1990;
70: 212-5.
18. Ortel B, Perl S, Kinaciyan T, et al. Comparison of
narrow-band (311 nm) UVB and broad-band UVA after oral or bath-water 8-methoxypsoralen
in the treatment of psoriasis. J Am Acad Dermatol 1993; 29: 736-40.
19. Collins P, Ferguson J. Narrowband (TL-01) UVB air-conditioned
phototherapy for atopic eczema in children. Br J Dermatol 1995;
133: 653-67.
20. British Photodermatology Group. An appraisal of narrowband
(TL-01) UVB phototherapy. British Photodermatology Group Workshop Report
(April 1996). Br J Dermatol 1997; 137: 327-30.
21. Young A. Carcinogenicity of UVB phototherapy assessed. Lancet
1995; 345: 1431-2.
22. De Gruijl FR. Long-term side effects and carcinigenesis risk
in UVB therapy. In: The fundamental bases of phototherapy. Hönigsmann
H, Jori G, Young AR, eds. Milan: OEMF SpA, 1996: 153-70.
23. Röcken M, Kerscher M, Volkenandt M, et al. Balneophototherapy.
Hautarzt 1995; 46: 437-50.
24. Kerscher M, Lehmann P, Plewig G. PUVA bath therapy. Indications
and practical application. Hautarzt 1994; 45: 526-8.
25. Vallat VP, Gilleaudeau P, Battat L, et al. PUVA bath
therapy strongly suppresses immunological and epidermal activation in
psoriasis: a possible cellular basis for remittive therapy. J Exp Med
1994; 180: 283-96.
26. Collins P, Rogers S. Bath-water compared with oral delivery
of 8-methoxypsoralen PUVA therapy for chronic plaque psoriasis. Br
J Dermatol 1992; 127: 392-5.
27. Schempp CM, Schöpf E, Simon JC. Phototesting in bath-PUVA:
marked reduction of 8-methoxypsoralen (8-MOP) activity within one hour
after an 8-MOP-bath. Photodermatol Photoimmunol Photomed 1996;
12: 100-2.
28. Neumann NJ, Kerscher M, Ruzicka T, et al. Evaluation
of PUVA bath phototoxicity. Acta Derm Venereol 1997; 77: 385-7.
29. Schempp CM, Müller H, Czech W, et al. Treatment
of chronic palmoplantar eczema with local bath-Puva therapy. J Am Acad
Dermatol 1997; 36: 733-7.
30. Muchenberger S, Schöpf E, Simon JC. The combination
of oral acitretin and bath PUVA for the treatment of severe psoriasis.
Br J Dermatol 1997; 137: 587-9.
31. Zimmermann J, Utermann S. Balneophototherapy in patients
with psoriasis and atopic dermatitis. Hautarzt 1994; 45: 849-53.
32. Dittmar HC, Pflieger D, Schempp CM, et al. Vergleichsstudie
Solebäder plus UVA/B versus UVA/B-Monotherapie bei Patienten
mit subakuter atopischer Dermatitis. Hautarzt 1999; 50: 649-53.
33. Streit T, Henseler T, Christophers E. Erste Erfahrungen mit
dem Erprobungsmodell "Ambulante Balneophototherapie". Dt Derm 1995;
43: 1005-8.
34. Wiedow O, Wiese F, Streit V, et al. Lesional elastase
activity in psoriasis, contact dermatitis, and atopic dermatitis. J
Invest Dermatol 1992; 99: 306-9.
35. Celerier P, Richard A, Litoux P, et al. Modulatory
effects of selenium and strontium salts on keratinocyte-derived inflammatory
cytokines. Arch Dermatol Res 1995; 287: 680-2.
36. Schempp CM, Blümke C, Schulte-Mönting J, et
al. The influence of different salt solutions on ultraviolet-B induced
skin erythema and delayed tanning. Hautarzt 1998; 49: 482-6.
37. Edelson R, Berger C, Gasparro F, et al. Treatment
of cutaneous T-cell-lymphoma by extracorporeal photochemotherapy. Preliminary
results. N Engl J Med 1987; 316: 297-303.
38. Balda BR, Konstantinow A, Starz H, et al. Extracorporeal
photochemotherapy as an effective treatment modality in chronic graft-versus-host
disease. J EurAcad Dermatol Venereol 1996; 7: 155-62.
39. Konstantinow A, Balda BR, Starz H, et al. Chronic
graft-versus-host disease: successful treatment with extracorporeal
photochemotherapy: a follow-up. Br J Dermatol 1996; 135: 1007-8.
40. Richter HI, Stege H, Ruzicka T, et al. Extracorporeal
photopheresis in the treatment of acute graft-versus-host disease.
J Am Acad Dermatol 1997; 36: 787-9.
41. Prinz B, Nachbar F, Plewig G. Treatment of severe atopic
dermatitis with extracorporeal photopheresis. Arch Dermatol Res
1994; 287: 48-52.
42. Schwartz J, Gonzalez J, Palangio M, et al. Extracorporeal
photochemotherapy in progressive systemic sclerosis: a follow-up study.
Int J Dermatol 1997; 36: 380-5.
43. Gollnick HP, Owsianowski M, Taube KM. Unresponsive severe
generalized pemphigus vulgaris successfully controlled by extracorporeal
photopheresis. J Am Acad Dermatol 1993; 28: 122-4.
44. Prinz B, Behrens W, Hölzle E, et al. Extracorporeal
photopheresis for the treatment of cutaneous T-cell-lymphoma - the Düsseldorf
and Munich experience. Arch Dermatol Res 1995; 287: 621-6.
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