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Photoinduced pompholyx: a report of 5 cases
Photoinduced pompholyx: A report of 5 cases Irene Man, MRCP, Sally H. Ibbotson, MD, and James Ferguson, MD Dundee, Scotland We describe 5 patients whose histories and investigation findings point toward a diagnosis of photoinduced hand pompholyx, a previously unreported condition. Several factors have been associated with the exacerbation of pompholyx, but no direct relationship with sunlight exposure has been reported. (J Am Acad Dermatol 2004;50:55-60.)
P
ompholyx is a common condition characterized by recurrent spongiotic vesicles affecting the hands and feet. A number of etiological factors, such as atopy,1,2 contact allergy,3,4 including allergy to ingested metals,5,6 psychological stress,7 and dermatophyte infection,8 have been associated with pompholyx. A positive correlation with systemic acetylsalicylic acid, smoking, and oral contraceptives was also observed in one study.9 In many cases, the cause remains unknown. It is well recognized that pompholyx can be exacerbated by hot weather. In a study of 104 patients, 41.3% reported worsening of attacks with the season, 29.8% with heat, 24% with humidity, 12.5% with cold, and 36.5% with hyperhidrosis.2 The role of sunlight, however, has never been reported. We describe 5 unusual white patients referred to the Photobiology Unit between 1989 and 2001 whose histories and investigative findings strongly suggest that long wavelength ultraviolet A (UVA) had an etiological role in the induction of pompholyx.
transmitted–sunlight induced pinhead-sized fluidfilled blisters on his palms, sides of fingers and dorsum of hands, with sparing of other sunlightexposed sites. The problem was apparently not associated with heat. While broad-spectrum sunscreens, such as Spectraban and RoC skin protection factor (SPF) 25 failed to offer benefit, leather gloves did prevent development of the eruption. He was not aware of possible contact allergens and had not been in contact with known phototoxic or photoallergic agents. He had no personal or family history of atopy and was not receiving systemic or topical therapy.
Case 1 A 30-year-old telephone engineer had a 13-year history of a perennial recurrent blistering eruption affecting both hands, consistent with idiopathic pompholyx. Over the prior 3 years, he had been aware of a new clinical development; approximately 2 hours of both direct sunlight and window-glass
Case 2 A 30-year-old secretary, with skin phototype III and no previous history of photosensitivity or pompholyx dermatitis, presented with a 5-year history of a recurrent summer eruption characterized by a pruritic erythematous “papular” eruption along the lateral borders of her fingers and, more prominently, over her second and third metacarpophalangeal joints. This mainly occurred when abroad but more recently in the United Kingdom. Two days of direct sunlight exposure could induce the eruption, which would last for 2 to 3 weeks. RoC total sunblock provided partial protection against the development of the eruption. She was unaffected by heat and had no history of contact allergy, drug ingestion, or personal or family background of atopy. In addition, she was unaware of contact with photosensitizers.
From the Photobiology Unit, Department of Dermatology, University of Dundee, Ninewells Hospital and Medical School. Funding sources: None. Conflict of interest: None identified. Accepted for publication August 9, 2002. Correspondence to: Professor James Ferguson, Photobiology Unit, Department of Dermatology, Ninewells Hospital and Medical School, Dundee, Scotland, DD1 9SY. E-mail: [email protected]. 0190-9622/$30.00 Copyright © 2004 by the American Academy of Dermatology, Inc. doi:10.1016/S0190-9622(03)00891-0
Case 3 A 51-year-old social worker with skin phototype I had a 2-year history of spring-to-autumn time photosensitivity, consistent with a diagnosis of polymorphic light eruption (PLE). Half an hour of direct or thin clothing–transmitted sunlight induced an intensely pruritic erythematous papular eruption on exposed sites of the V of her neck, dorsa of hands, forearms, and legs, with sparing of her face. The eruption would appear after a few hours and heal over a week without scarring. In addition, she de-
CASE REPORTS
55
56 Man, Ibbotson, and Ferguson
scribed tiny fluid-filled blisters along the lateral borders of her fingers. Sunscreens provided minimal protection. She had no history of atopy, contact allergy, drug ingestion, or contact with potential photosensitizers. Case 4 A 68-year-old woman with skin phototype II gave a 3-year history of an itchy eruption on her hands. The eruption occurred only when she was abroad and resolved 2 to 3 weeks after her return to the United Kingdom. After 2 to 3 days of direct sunlight exposure, she developed erythema and pruritus on her knuckles, followed by “hardening” along the sides of fingers and palms. She was not aware of blisters or papules. Subsequently, her skin flaked and peeled. A similar eruption occurred simultaneously on her heels and beneath her metatarsophalangeal joints on 2 occasions. No previous history of photosensitivity or contact allergy was apparent. Although she had no personal history of atopy, there was a family background of atopic dermatitis. She was taking no medication. Case 5 A 53-year-old maintenance engineer with skin phototype I first developed summer photosensitivity at age 43. After 3 days of sunlight exposure, intensely itchy tiny blisters appeared along the sides and dorsal aspect of his fingers. The palms, feet, and other photoexposed sites were spared. Sunscreens, especially SPF 50, were helpful in preventing the eruption. He had a history of rosacea but was otherwise well and was receiving no medication. He had no personal or family background of atopy.
INVESTIGATIONS All patients were phototested with a high-pressure 1600 W xenon arc monochromator. Irradiance was measured with a thermopile and digital voltmeter. Eight-millimeter circular irradiation fields on the upper portion of each subject’s untanned back skin were exposed to defined dose series at 305 ⫾ 5 nm, 335 ⫾ 30 nm, 365 ⫾ 30 nm, 400 ⫾ 30 nm, and 430 ⫾ 30 nm wavebands. Erythema was recorded at 7 and 24 hours. If erythema was evident at any wavebands at 24 hours, further doses were given to determine the minimal erythema dose, which was then compared with a normal population databank. Provocation with UVA was carried out in all patients with a high-pressure metal halide lamp (Dr Ho¨ nle Portable Dermalight 200, filter H1, spectral output 320-400 nm, Ho¨ nle UV (UK) Ltd, West Midlands, UK). Irradiance was measured with a Waldmann UV meter. On a previously affected site on the lateral border of finger, dorsal hands, thenar or hy-
J AM ACAD DERMATOL JANUARY 2004
pothenar eminence, irradiation fields (4 ⫻ 2 cm or 8 ⫻ 2 cm) were exposed to 15-25 J/cm2 UVA. Test sites were examined at 24 hours, and, if no response was detected, a further dose of UVA was given at the same site for up to 3 consecutive days. To confirm or exclude the diagnosis of PLE, UVA provocation was also conducted on the extensor forearms or dorsa of the hand in 3 patients. Biopsy specimens of a provoked vesicle were taken in 2 subjects. Sections were stained with hematoxylin and eosin and examined under the light microscope. An attempt was made to induce the vesicular reaction with narrowband ultraviolet B (UVB, TL-01; 311-313 nm) in 1 patient and with heat in 3. In patient 1, 3 test areas on the hand were exposed to suberythemogenic TL-01 UVB doses (150, 250, and 400 mJ/cm2). Irradiated sites were examined at 24 hours. In the same patient, heat provocation was conducted with a test tube containing hot water. Heat provocation was carried out in patients 3 and 4 with an infrared source (Philips Infraphil HP 3690 lamp, Philips, Hamilton, Scotland). Test sites on the hands were exposed to 10 minutes of infrared irradiation at a distance of 30 cm and reactions were noted at 24 hours. Patch testing to the European Standard Series was carried out in all patients. Additionally, patch testing to corticosteroids, compositae oleoresins and cosmetic series were conducted in 2 patients. Agents were applied on Finn Chambers and occluded for 48 hours. Readings were recorded at 72 and 96 hours. Photopatch testing to a sunscreen series was performed in 2 patients. Two identical series were applied on the mid back and occluded for 24 hours. With a broad-spectrum UVA fluorescent lamp (MPD PUVA unit equipped with 10 ⫻ 2-ft Waldmann F15W/T8 tubes, constructed by the Medical Physics Department, Ninewells Hospital, peak wavelength 350 nm, range 320-400 nm), 1 set was irradiated with 5 J/cm2 UVA, and the other set was covered. Readings were recorded at 24 and 48 hours. Serology was performed for antinuclear, anti-Ro, and anti-La antibodies in all subjects. Additionally, porphyrin scan analysis was performed in 4 patients, and total Ig E was measured in 2. A summary of the patients’ details is shown in Table I.
RESULTS The results are summarized in Table II. Monochromator phototesting was normal in 3 of the 5 subjects. Patients 3 and 5 had photosensitivity in the UVA wavebands (Table III). UVA provocation on a previously affected site induced a positive vesicular response in all patients. In patient 1, erythema was
Man, Ibbotson, and Ferguson 57
J AM ACAD DERMATOL VOLUME 50, NUMBER 1
Table I. Patients’ details
Case No.
Hx of contact allergy or contact with potential photosensitisers
Hx of other photosensitivity disorder
Personal or family history of atopy
Duration of symptoms (y)/status
Sex/Age at onset of photosensitivity (y)
Provocation: sunlight/heat
1
M/27
No
No
No
15/ongoing problems
2
F/25
Direct and windowglass/no Direct/no
No
No
No
3
F/49
Direct/no
No
4
F/65
Direct/no
No
No
9/symptom-free since pregnancy 3/symptom-free since TL-01 UVB desensitization for PLE 3/ongoing problems
5
M/43
Direct/no
No
No
Polymorphic light eruption
No
Family history of atopy Total IgE 7.9 ku/l No 10/ongoing problems Total IgE 44.7 ku/l
F, Female; Hx, history; M, male.
Table II. Summary of investigations Case No.
1
2 3 4 5
Monochromator phototesting
Site/result of UVA provocation (dose)
Histology of provoked vesicle
Spongiotic Extensor forearm/negative dermatitis Thenar eminence/vesicular (single exposure to 15 and 20 J/cm2 on 2 separate occasions) Normal Extensor forearm/negative — Lateral border of finger/vesicular (25 J/cm2 on 3 consecutive days) Reduced MED at Dorsal hand/papular (PLE) Spongiotic 335-400 ⫾ 30 nm Lateral border of finger/vesicular (25 dermatitis J/cm2 on 2 consecutive days) Normal Dorsal hand/papulovesicular — Hypothenar eminence/vesicular (single exposure to 25 J/cm2) Reduced MED at Lateral border of finger/vesicular (25 — 335-365 ⫾ 30 nm J/cm2 on 3 consecutive days)
Normal
Patch testing
Photopatch testing to sunscreen series
ESS: negative
—
ESS/facial/cosmetic series: negative
—
ESS/plant/corticosteroid series: negative
—
ESS: grade 3 reactions to nickel, quaternium and phenoxyethanol ESS: negative
Negative Negative
ESS, European Standards Series; MED, minimal erythema dose.
noted at the provocation site 24 hours after 20 J/cm2 UVA, followed by development of vesicles localized to the test site, with marked demarcation from adjacent unirradiated skin (Fig 1). The lesions appeared maximally at 120 hours. The response was reproduced on repeated provocation with 15 J/cm2. In the other 4 patients, doses up to 25 J/cm2 on 1 to 3 consecutive days were required to elicit the vesicular reaction, which was apparent 24 hours after the last irradiation. The morphology of the responses was in keeping with pompholyx. Biopsy results of a provoked vesicle in patients 1 and 3 confirmed a spongiotic dermatitis reaction (Fig 2). Sections
showed acanthosis, spongiosis, and vesicle formation within the epidermis and a perivascular mononuclear inflammatory infiltrate in the dermis. Interestingly, patient 3 also had PLE, and identical UVA provocation on the dorsum of her hand produced a different morphological and histological picture compared with the provoked pompholyx reaction on her finger. Clinically, a papular response was induced, and the histology was nonspecific, with no dermatitis features. In those with a negative PLE history, UVA provocation on the extensor forearms failed to elicit an abnormal reaction. TL-01 and heat provocation results were also negative.
58 Man, Ibbotson, and Ferguson
J AM ACAD DERMATOL JANUARY 2004
Table III. Abnormal UVA photosensitivity in 2 patients
Fig 1. UVA provocation site (patient 1). Vesicular eruption localized to site of irradiation with sharp demarcation from adjacent unirradiated skin. Reaction occurred after single exposure to 20J/cm2 UVA.
Fig 2. Histology of UVA provocation site of patient 1, showing features of acute vesicular dermatitis.
All subjects had negative patch-test results except for patient 4. She demonstrated a grade 3 reaction to nickel, quaternium, and phenoxyethanol, none of which was relevant. Photopatch results in patients 4 and 5 were negative. Routine hematology and biochemical profiles showed no significant abnormalities in all patents. Lupus serology and plasma porphyrin scans were negative. Total IgG, checked in patients 4 and 5, was within the normal range.
CONTROL SUBJECTS Ten subjects with idiopathic pompholyx were randomly selected, and UVA provocation was performed on their hands. Test sites were irradiated with 25 J/cm2 UVA (same light source as patients 1-5) on 3 consecutive days. No abnormal responses were induced 24 hours after the third irradiation.
DISCUSSION Although it is commonly observed that pompholyx exacerbations are more frequent during the summer months, a direct relationship with sunlight exposure has not been reported. The unique history of induction of pompholyx by sunlight, as con-
Wavelength (nm)
Lowest value in normal population (mJ/cm2)
335 ⫾ 30 365 ⫾ 30 400 ⫾ 30
1800 8200 47,000
Minimal erythema dose/no response (mJ/cm2) Patient 3
Patient 5
1000/820 5600/4700 22,000/18,000
330/390 4700/5600 ⬎47,000
firmed on investigations, suggests that this is another cause of vesicular hand dermatitis. The provocation of the eruption by UVA, with the morphology and histology of a vesicular dermatitis, confirms true photosensitivity rather than photoaggravation. This, in contrast to the therapeutic effectiveness of UVB phototherapy and photochemotherapy in the treatment of the well-recognized form of pompholyx,10,11 further subdivides these photoinduced cases from the more common form. Why should this phenomenon occur in these patients? There appears to be no common factor or precipitating event. Patient 1 had a preceding history of perennial pompholyx, patient 3 had concomitant PLE, and the condition arose without a history of pompholyx or photosensitivity in the other 3. The association of nickel allergy and pompholyx is well recognized.5 Although patient 4’s patch test showed a positive reaction to nickel, in addition to quaternium and phenoxyethanol, she was unaware of a relationship between the contact allergens and the sunlight-related exacerbation of the hand eruption. As heat is often a reported aggravating factor in pompholyx, we attempted to provoke the eruption using the Philips Infraphil HP 3690 lamp (patients 3 and 4). With a 10-minute irradiation protocol, which provides sufficient heat to induce an uncomfortable, hot sensation, no vesicular reaction was induced at 24 hours. Although little is known about this heat source, the negative result strongly suggests that heat was not a provoking factor in our patients. With a more simple method of heat induction, no abnormal response was provoked with a test tube containing hot water (patient 1). These findings, in keeping with the patients’ histories, suggested that heat is not responsible for photo-induced pompholyx. The association of abnormal photosensitivity and pompholyx has previously been reported in patients with piroxicam-induced photosensitivity.12-15 McKerrow and Greig13 reported that 6 of 11 cases of piroxicam-induced photosensitivity had features of vesicular hand dermatitis, 2 of whom had persistent problems after withdrawal of the drug. The mecha-
J AM ACAD DERMATOL VOLUME 50, NUMBER 1
nism involved was not well defined, but photoallergy has been implicated. Photoallergy, a type IV hypersensitivity response, requires the addition of UVA irradiation to generate complete haptens or antigens for the T-cell–mediated immune response.16 The absence of a nonsteroidal anti-inflammatory or other drug history in the presented cases excluded this possibility. There might have been persistence of a photoallergen from previous exposure. Topically applied substances, such as epoxy resins,17 buclosamide,18 and Multifungin19 have been reported to induce persistent localized photosensitivity. None of our patients recalled a history of contact with potential photosensitisers. In addition, sunscreen photopatch testing, which was set up in our department in 1991, conducted in 2 subjects, failed to identify a sunscreen photoallergen. Although these cases are presented as photoinduced pompholyx, it is possible that they are an unrelated condition with a pompholyx-like presentation. One such disorder that should be considered is vesicular PLE. PLE is a common idiopathic photodermatosis that predominantly affects women. Different clinical morphologies exist, including a vesicular variant. The papular form is the most common. Typically, lesions occur on photoexposed sites, but chronically exposed skin, such as face and dorsal hands, can be spared.20 In the presented cases, the development of the vesicular eruption on the hands—in particular, the lateral border of the fingers and palms—without involvement of other exposed sites, makes this diagnosis unlikely. Additionally, the negative PLE provocation tests in 2 of 3 patients provides further support against the diagnosis of PLE. The third patient had concurrent classic PLE, and the PLE provocation site on her dorsal hands produced a different clinical morphology and histological appearance from the provocation site on her finger. PLE can exhibit a variety of histological appearances. In the vesicular variant, edema can occur within the epidermis and/or subepidermally, along with a superficial and deep dermal inflammatory infiltrate.21,22 In contrast, histology of pompholyx characteristically shows spongiotic intraepidermal vesiculation with only a superficial inflammatory infiltrate.23 In our patient, these pompholyx features were produced with the UVA provocation on the lateral border of her finger, whereas the PLE induction site on the dorsum of her hand produced a different histological picture with only nonspecific features. Our management of these patients was broadly similar to those with pompholyx, with the addition of photoprotection as a preventive measure. Because the hands are involved, the use of sunscreens is often impractical. An alternative approach is to
Man, Ibbotson, and Ferguson 59
encourage patients to wear gloves and minimize sunlight exposure. The clear plastic Museum 200 film (Bonwyke Window Films, Hampshire, UK) might also be useful,24 particularly for those with a problem when driving. Patient 3, who received springtime TL-01 phototherapy as prophylactic treatment for PLE, also obtained benefit for the pompholyx. Although the mechanism involved is not known, the induction of artificial hardening might be considered a therapeutic option in patients with photoinduced pompholyx who cannot avoid sunlight. As pompholyx is a common disorder, the identification of only 5 cases of photoinduced pompholyx over the period 1989-2001 suggests that this is a rare subset. It is likely, however, that this is an underestimation, because patients with seasonal variations are seldom referred to our unit for phototesting. We suggest that patients with pompholyx presenting with seasonal variation and frequent exacerbations during summer should be considered for further investigation with phototesting. We thank Drs D. Dick, W. S. Douglas, C. S. Munro, and R. S. Dawe for referring their patients for investigation and Dr J. G. Lowe and A. T. Evans for their comments on the histology and the production of histology slides. REFERENCES 1. Oddoze L, Temime P. Dyshidrosis and atopy. Bull Soc Fr Dermatol Syphilugr 1968;75:378-80. 2. Lodi A, Betti R, Chiarelli G, Urbani CE, Crosti C. Epidemiological, clinical and allergological observations on pompholyx. Contact Dermatitis 1992;26:17-21. 3. Meneghini CL, Angelini G. Contact and microbial allergy in pompholyx. Contact Dermatitis 1974;5:46-50. 4. Menne T, Hjorth N. Pompholyx-dyshidrotic eczema. Semin Dermatol 1983;2:75-80. 5. Christensen OB, Moller H. Nickel allergy and hand eczema. Contact Dermatitis 1975;1:129-35. 6. Veien NK, Kaaber K. Nickel, cobalt and chromium sensitivity in patients with pompholyx (dyshidrotic eczema). Contact Dermatitis 1979;5:371-4. 7. Kellum RE. Dyshidrotic hand eczema. A psychotherapeutic approach. Cutis 1975;16:875-8. 8. Tagami H, Watanabe S, Ofugi S, Minami K. Trichophyton contact sensitivity in patients with dermatophytosis. Arch Dermatol 1977;113:1409-14. 9. Edman B. Palmar eczema: a pathogenetic role for acetylsalicylic acid, contraceptives and smoking? Acta Derm Venereol 1988; 68:402-7. 10. Rosen K, Mobacken H, Swanbeck G. Chronic eczematous dermatitis of the hands: a comparison of PUVA and UVB treatment. Acta Derm Venereol 1987;67:48-54. 11. Tegner E, Thelin I. PUVA treatment of chronic eczematous dermatitis of the palms and soles. Acta Derm Venereol 1985;65: 451-3. 12. Anonide A, Usiglio D, Pestarina A, Massone L. Droxicam photosensitivity with dyshidrotic hand dermatitis. Int J Dermatol 1997;36:318-20. 13. McKerrow K, Greig DE. Piroxicam-induced photosensitive dermatitis. J Am Acad Dermatol 1986;15:1237-41.
60 Man, Ibbotson, and Ferguson
14. Braunstein BL. Dyshidrotic eczema associated with piroxicam photosensitivity. Cutis 1985;35:485-6. 15. Youn JI, Lee HG, Yeo UC, Lee YS. Piroxicam photosensitivity associated with vesicular hand dermatitis. Clin Exp Dermatol 1993; 18:52-4. 16. Gona´lez E, Gona´lez S. Drug photosensitivity, idiopathic photodermatoses, and sunscreens. J Am Acad Dermatol 1996;35:87185. 17. Allen H, Kaidbey K. Persistent photosensitivity following occupational exposure to epoxy resin. Arch Dermatol 1979;115: 1307-10. 18. Burry JN. Persistent light reaction from buclosamide. Arch Dermatol 1970;101:95-7.
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19. Burry JN. Photoallergies to fenticlor and Multifungin. Arch Dermatol 1967;95:287-91. 20. Frain-Bell W. The idiopathic photodermatoses. Cutaneous photobiology. Oxford: Oxford University Press; 1985. p. 24-59. 21. Hood AF, Elpern DJ, Morison WL. Histopathologic findings in papulovesicular light eruption. J Cutan Pathol 1986;13:13-21. 22. Weedon D. Vesiculobullous reaction pattern. In: Skin pathology. Edinburgh: Churchill Livingstone; 1997. p. 133. 23. Weedon D. Pompholyx. In: Skin pathology. Edinburgh: Churchill Livingstone; 1997. p. 95. 24. Dawe RS, Russell S, Ferguson J. Borrowing from museums and industry: two photoprotective devices. Br J Dermatol 1996;135: 1016-7.
P
ompholyx is a common condition characterized by recurrent spongiotic vesicles affecting the hands and feet. A number of etiological factors, such as atopy,1,2 contact allergy,3,4 including allergy to ingested metals,5,6 psychological stress,7 and dermatophyte infection,8 have been associated with pompholyx. A positive correlation with systemic acetylsalicylic acid, smoking, and oral contraceptives was also observed in one study.9 In many cases, the cause remains unknown. It is well recognized that pompholyx can be exacerbated by hot weather. In a study of 104 patients, 41.3% reported worsening of attacks with the season, 29.8% with heat, 24% with humidity, 12.5% with cold, and 36.5% with hyperhidrosis.2 The role of sunlight, however, has never been reported. We describe 5 unusual white patients referred to the Photobiology Unit between 1989 and 2001 whose histories and investigative findings strongly suggest that long wavelength ultraviolet A (UVA) had an etiological role in the induction of pompholyx.
transmitted–sunlight induced pinhead-sized fluidfilled blisters on his palms, sides of fingers and dorsum of hands, with sparing of other sunlightexposed sites. The problem was apparently not associated with heat. While broad-spectrum sunscreens, such as Spectraban and RoC skin protection factor (SPF) 25 failed to offer benefit, leather gloves did prevent development of the eruption. He was not aware of possible contact allergens and had not been in contact with known phototoxic or photoallergic agents. He had no personal or family history of atopy and was not receiving systemic or topical therapy.
Case 1 A 30-year-old telephone engineer had a 13-year history of a perennial recurrent blistering eruption affecting both hands, consistent with idiopathic pompholyx. Over the prior 3 years, he had been aware of a new clinical development; approximately 2 hours of both direct sunlight and window-glass
Case 2 A 30-year-old secretary, with skin phototype III and no previous history of photosensitivity or pompholyx dermatitis, presented with a 5-year history of a recurrent summer eruption characterized by a pruritic erythematous “papular” eruption along the lateral borders of her fingers and, more prominently, over her second and third metacarpophalangeal joints. This mainly occurred when abroad but more recently in the United Kingdom. Two days of direct sunlight exposure could induce the eruption, which would last for 2 to 3 weeks. RoC total sunblock provided partial protection against the development of the eruption. She was unaffected by heat and had no history of contact allergy, drug ingestion, or personal or family background of atopy. In addition, she was unaware of contact with photosensitizers.
From the Photobiology Unit, Department of Dermatology, University of Dundee, Ninewells Hospital and Medical School. Funding sources: None. Conflict of interest: None identified. Accepted for publication August 9, 2002. Correspondence to: Professor James Ferguson, Photobiology Unit, Department of Dermatology, Ninewells Hospital and Medical School, Dundee, Scotland, DD1 9SY. E-mail: [email protected]. 0190-9622/$30.00 Copyright © 2004 by the American Academy of Dermatology, Inc. doi:10.1016/S0190-9622(03)00891-0
Case 3 A 51-year-old social worker with skin phototype I had a 2-year history of spring-to-autumn time photosensitivity, consistent with a diagnosis of polymorphic light eruption (PLE). Half an hour of direct or thin clothing–transmitted sunlight induced an intensely pruritic erythematous papular eruption on exposed sites of the V of her neck, dorsa of hands, forearms, and legs, with sparing of her face. The eruption would appear after a few hours and heal over a week without scarring. In addition, she de-
CASE REPORTS
55
56 Man, Ibbotson, and Ferguson
scribed tiny fluid-filled blisters along the lateral borders of her fingers. Sunscreens provided minimal protection. She had no history of atopy, contact allergy, drug ingestion, or contact with potential photosensitizers. Case 4 A 68-year-old woman with skin phototype II gave a 3-year history of an itchy eruption on her hands. The eruption occurred only when she was abroad and resolved 2 to 3 weeks after her return to the United Kingdom. After 2 to 3 days of direct sunlight exposure, she developed erythema and pruritus on her knuckles, followed by “hardening” along the sides of fingers and palms. She was not aware of blisters or papules. Subsequently, her skin flaked and peeled. A similar eruption occurred simultaneously on her heels and beneath her metatarsophalangeal joints on 2 occasions. No previous history of photosensitivity or contact allergy was apparent. Although she had no personal history of atopy, there was a family background of atopic dermatitis. She was taking no medication. Case 5 A 53-year-old maintenance engineer with skin phototype I first developed summer photosensitivity at age 43. After 3 days of sunlight exposure, intensely itchy tiny blisters appeared along the sides and dorsal aspect of his fingers. The palms, feet, and other photoexposed sites were spared. Sunscreens, especially SPF 50, were helpful in preventing the eruption. He had a history of rosacea but was otherwise well and was receiving no medication. He had no personal or family background of atopy.
INVESTIGATIONS All patients were phototested with a high-pressure 1600 W xenon arc monochromator. Irradiance was measured with a thermopile and digital voltmeter. Eight-millimeter circular irradiation fields on the upper portion of each subject’s untanned back skin were exposed to defined dose series at 305 ⫾ 5 nm, 335 ⫾ 30 nm, 365 ⫾ 30 nm, 400 ⫾ 30 nm, and 430 ⫾ 30 nm wavebands. Erythema was recorded at 7 and 24 hours. If erythema was evident at any wavebands at 24 hours, further doses were given to determine the minimal erythema dose, which was then compared with a normal population databank. Provocation with UVA was carried out in all patients with a high-pressure metal halide lamp (Dr Ho¨ nle Portable Dermalight 200, filter H1, spectral output 320-400 nm, Ho¨ nle UV (UK) Ltd, West Midlands, UK). Irradiance was measured with a Waldmann UV meter. On a previously affected site on the lateral border of finger, dorsal hands, thenar or hy-
J AM ACAD DERMATOL JANUARY 2004
pothenar eminence, irradiation fields (4 ⫻ 2 cm or 8 ⫻ 2 cm) were exposed to 15-25 J/cm2 UVA. Test sites were examined at 24 hours, and, if no response was detected, a further dose of UVA was given at the same site for up to 3 consecutive days. To confirm or exclude the diagnosis of PLE, UVA provocation was also conducted on the extensor forearms or dorsa of the hand in 3 patients. Biopsy specimens of a provoked vesicle were taken in 2 subjects. Sections were stained with hematoxylin and eosin and examined under the light microscope. An attempt was made to induce the vesicular reaction with narrowband ultraviolet B (UVB, TL-01; 311-313 nm) in 1 patient and with heat in 3. In patient 1, 3 test areas on the hand were exposed to suberythemogenic TL-01 UVB doses (150, 250, and 400 mJ/cm2). Irradiated sites were examined at 24 hours. In the same patient, heat provocation was conducted with a test tube containing hot water. Heat provocation was carried out in patients 3 and 4 with an infrared source (Philips Infraphil HP 3690 lamp, Philips, Hamilton, Scotland). Test sites on the hands were exposed to 10 minutes of infrared irradiation at a distance of 30 cm and reactions were noted at 24 hours. Patch testing to the European Standard Series was carried out in all patients. Additionally, patch testing to corticosteroids, compositae oleoresins and cosmetic series were conducted in 2 patients. Agents were applied on Finn Chambers and occluded for 48 hours. Readings were recorded at 72 and 96 hours. Photopatch testing to a sunscreen series was performed in 2 patients. Two identical series were applied on the mid back and occluded for 24 hours. With a broad-spectrum UVA fluorescent lamp (MPD PUVA unit equipped with 10 ⫻ 2-ft Waldmann F15W/T8 tubes, constructed by the Medical Physics Department, Ninewells Hospital, peak wavelength 350 nm, range 320-400 nm), 1 set was irradiated with 5 J/cm2 UVA, and the other set was covered. Readings were recorded at 24 and 48 hours. Serology was performed for antinuclear, anti-Ro, and anti-La antibodies in all subjects. Additionally, porphyrin scan analysis was performed in 4 patients, and total Ig E was measured in 2. A summary of the patients’ details is shown in Table I.
RESULTS The results are summarized in Table II. Monochromator phototesting was normal in 3 of the 5 subjects. Patients 3 and 5 had photosensitivity in the UVA wavebands (Table III). UVA provocation on a previously affected site induced a positive vesicular response in all patients. In patient 1, erythema was
Man, Ibbotson, and Ferguson 57
J AM ACAD DERMATOL VOLUME 50, NUMBER 1
Table I. Patients’ details
Case No.
Hx of contact allergy or contact with potential photosensitisers
Hx of other photosensitivity disorder
Personal or family history of atopy
Duration of symptoms (y)/status
Sex/Age at onset of photosensitivity (y)
Provocation: sunlight/heat
1
M/27
No
No
No
15/ongoing problems
2
F/25
Direct and windowglass/no Direct/no
No
No
No
3
F/49
Direct/no
No
4
F/65
Direct/no
No
No
9/symptom-free since pregnancy 3/symptom-free since TL-01 UVB desensitization for PLE 3/ongoing problems
5
M/43
Direct/no
No
No
Polymorphic light eruption
No
Family history of atopy Total IgE 7.9 ku/l No 10/ongoing problems Total IgE 44.7 ku/l
F, Female; Hx, history; M, male.
Table II. Summary of investigations Case No.
1
2 3 4 5
Monochromator phototesting
Site/result of UVA provocation (dose)
Histology of provoked vesicle
Spongiotic Extensor forearm/negative dermatitis Thenar eminence/vesicular (single exposure to 15 and 20 J/cm2 on 2 separate occasions) Normal Extensor forearm/negative — Lateral border of finger/vesicular (25 J/cm2 on 3 consecutive days) Reduced MED at Dorsal hand/papular (PLE) Spongiotic 335-400 ⫾ 30 nm Lateral border of finger/vesicular (25 dermatitis J/cm2 on 2 consecutive days) Normal Dorsal hand/papulovesicular — Hypothenar eminence/vesicular (single exposure to 25 J/cm2) Reduced MED at Lateral border of finger/vesicular (25 — 335-365 ⫾ 30 nm J/cm2 on 3 consecutive days)
Normal
Patch testing
Photopatch testing to sunscreen series
ESS: negative
—
ESS/facial/cosmetic series: negative
—
ESS/plant/corticosteroid series: negative
—
ESS: grade 3 reactions to nickel, quaternium and phenoxyethanol ESS: negative
Negative Negative
ESS, European Standards Series; MED, minimal erythema dose.
noted at the provocation site 24 hours after 20 J/cm2 UVA, followed by development of vesicles localized to the test site, with marked demarcation from adjacent unirradiated skin (Fig 1). The lesions appeared maximally at 120 hours. The response was reproduced on repeated provocation with 15 J/cm2. In the other 4 patients, doses up to 25 J/cm2 on 1 to 3 consecutive days were required to elicit the vesicular reaction, which was apparent 24 hours after the last irradiation. The morphology of the responses was in keeping with pompholyx. Biopsy results of a provoked vesicle in patients 1 and 3 confirmed a spongiotic dermatitis reaction (Fig 2). Sections
showed acanthosis, spongiosis, and vesicle formation within the epidermis and a perivascular mononuclear inflammatory infiltrate in the dermis. Interestingly, patient 3 also had PLE, and identical UVA provocation on the dorsum of her hand produced a different morphological and histological picture compared with the provoked pompholyx reaction on her finger. Clinically, a papular response was induced, and the histology was nonspecific, with no dermatitis features. In those with a negative PLE history, UVA provocation on the extensor forearms failed to elicit an abnormal reaction. TL-01 and heat provocation results were also negative.
58 Man, Ibbotson, and Ferguson
J AM ACAD DERMATOL JANUARY 2004
Table III. Abnormal UVA photosensitivity in 2 patients
Fig 1. UVA provocation site (patient 1). Vesicular eruption localized to site of irradiation with sharp demarcation from adjacent unirradiated skin. Reaction occurred after single exposure to 20J/cm2 UVA.
Fig 2. Histology of UVA provocation site of patient 1, showing features of acute vesicular dermatitis.
All subjects had negative patch-test results except for patient 4. She demonstrated a grade 3 reaction to nickel, quaternium, and phenoxyethanol, none of which was relevant. Photopatch results in patients 4 and 5 were negative. Routine hematology and biochemical profiles showed no significant abnormalities in all patents. Lupus serology and plasma porphyrin scans were negative. Total IgG, checked in patients 4 and 5, was within the normal range.
CONTROL SUBJECTS Ten subjects with idiopathic pompholyx were randomly selected, and UVA provocation was performed on their hands. Test sites were irradiated with 25 J/cm2 UVA (same light source as patients 1-5) on 3 consecutive days. No abnormal responses were induced 24 hours after the third irradiation.
DISCUSSION Although it is commonly observed that pompholyx exacerbations are more frequent during the summer months, a direct relationship with sunlight exposure has not been reported. The unique history of induction of pompholyx by sunlight, as con-
Wavelength (nm)
Lowest value in normal population (mJ/cm2)
335 ⫾ 30 365 ⫾ 30 400 ⫾ 30
1800 8200 47,000
Minimal erythema dose/no response (mJ/cm2) Patient 3
Patient 5
1000/820 5600/4700 22,000/18,000
330/390 4700/5600 ⬎47,000
firmed on investigations, suggests that this is another cause of vesicular hand dermatitis. The provocation of the eruption by UVA, with the morphology and histology of a vesicular dermatitis, confirms true photosensitivity rather than photoaggravation. This, in contrast to the therapeutic effectiveness of UVB phototherapy and photochemotherapy in the treatment of the well-recognized form of pompholyx,10,11 further subdivides these photoinduced cases from the more common form. Why should this phenomenon occur in these patients? There appears to be no common factor or precipitating event. Patient 1 had a preceding history of perennial pompholyx, patient 3 had concomitant PLE, and the condition arose without a history of pompholyx or photosensitivity in the other 3. The association of nickel allergy and pompholyx is well recognized.5 Although patient 4’s patch test showed a positive reaction to nickel, in addition to quaternium and phenoxyethanol, she was unaware of a relationship between the contact allergens and the sunlight-related exacerbation of the hand eruption. As heat is often a reported aggravating factor in pompholyx, we attempted to provoke the eruption using the Philips Infraphil HP 3690 lamp (patients 3 and 4). With a 10-minute irradiation protocol, which provides sufficient heat to induce an uncomfortable, hot sensation, no vesicular reaction was induced at 24 hours. Although little is known about this heat source, the negative result strongly suggests that heat was not a provoking factor in our patients. With a more simple method of heat induction, no abnormal response was provoked with a test tube containing hot water (patient 1). These findings, in keeping with the patients’ histories, suggested that heat is not responsible for photo-induced pompholyx. The association of abnormal photosensitivity and pompholyx has previously been reported in patients with piroxicam-induced photosensitivity.12-15 McKerrow and Greig13 reported that 6 of 11 cases of piroxicam-induced photosensitivity had features of vesicular hand dermatitis, 2 of whom had persistent problems after withdrawal of the drug. The mecha-
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nism involved was not well defined, but photoallergy has been implicated. Photoallergy, a type IV hypersensitivity response, requires the addition of UVA irradiation to generate complete haptens or antigens for the T-cell–mediated immune response.16 The absence of a nonsteroidal anti-inflammatory or other drug history in the presented cases excluded this possibility. There might have been persistence of a photoallergen from previous exposure. Topically applied substances, such as epoxy resins,17 buclosamide,18 and Multifungin19 have been reported to induce persistent localized photosensitivity. None of our patients recalled a history of contact with potential photosensitisers. In addition, sunscreen photopatch testing, which was set up in our department in 1991, conducted in 2 subjects, failed to identify a sunscreen photoallergen. Although these cases are presented as photoinduced pompholyx, it is possible that they are an unrelated condition with a pompholyx-like presentation. One such disorder that should be considered is vesicular PLE. PLE is a common idiopathic photodermatosis that predominantly affects women. Different clinical morphologies exist, including a vesicular variant. The papular form is the most common. Typically, lesions occur on photoexposed sites, but chronically exposed skin, such as face and dorsal hands, can be spared.20 In the presented cases, the development of the vesicular eruption on the hands—in particular, the lateral border of the fingers and palms—without involvement of other exposed sites, makes this diagnosis unlikely. Additionally, the negative PLE provocation tests in 2 of 3 patients provides further support against the diagnosis of PLE. The third patient had concurrent classic PLE, and the PLE provocation site on her dorsal hands produced a different clinical morphology and histological appearance from the provocation site on her finger. PLE can exhibit a variety of histological appearances. In the vesicular variant, edema can occur within the epidermis and/or subepidermally, along with a superficial and deep dermal inflammatory infiltrate.21,22 In contrast, histology of pompholyx characteristically shows spongiotic intraepidermal vesiculation with only a superficial inflammatory infiltrate.23 In our patient, these pompholyx features were produced with the UVA provocation on the lateral border of her finger, whereas the PLE induction site on the dorsum of her hand produced a different histological picture with only nonspecific features. Our management of these patients was broadly similar to those with pompholyx, with the addition of photoprotection as a preventive measure. Because the hands are involved, the use of sunscreens is often impractical. An alternative approach is to
Man, Ibbotson, and Ferguson 59
encourage patients to wear gloves and minimize sunlight exposure. The clear plastic Museum 200 film (Bonwyke Window Films, Hampshire, UK) might also be useful,24 particularly for those with a problem when driving. Patient 3, who received springtime TL-01 phototherapy as prophylactic treatment for PLE, also obtained benefit for the pompholyx. Although the mechanism involved is not known, the induction of artificial hardening might be considered a therapeutic option in patients with photoinduced pompholyx who cannot avoid sunlight. As pompholyx is a common disorder, the identification of only 5 cases of photoinduced pompholyx over the period 1989-2001 suggests that this is a rare subset. It is likely, however, that this is an underestimation, because patients with seasonal variations are seldom referred to our unit for phototesting. We suggest that patients with pompholyx presenting with seasonal variation and frequent exacerbations during summer should be considered for further investigation with phototesting. We thank Drs D. Dick, W. S. Douglas, C. S. Munro, and R. S. Dawe for referring their patients for investigation and Dr J. G. Lowe and A. T. Evans for their comments on the histology and the production of histology slides. REFERENCES 1. Oddoze L, Temime P. Dyshidrosis and atopy. Bull Soc Fr Dermatol Syphilugr 1968;75:378-80. 2. Lodi A, Betti R, Chiarelli G, Urbani CE, Crosti C. Epidemiological, clinical and allergological observations on pompholyx. Contact Dermatitis 1992;26:17-21. 3. Meneghini CL, Angelini G. Contact and microbial allergy in pompholyx. Contact Dermatitis 1974;5:46-50. 4. Menne T, Hjorth N. Pompholyx-dyshidrotic eczema. Semin Dermatol 1983;2:75-80. 5. Christensen OB, Moller H. Nickel allergy and hand eczema. Contact Dermatitis 1975;1:129-35. 6. Veien NK, Kaaber K. Nickel, cobalt and chromium sensitivity in patients with pompholyx (dyshidrotic eczema). Contact Dermatitis 1979;5:371-4. 7. Kellum RE. Dyshidrotic hand eczema. A psychotherapeutic approach. Cutis 1975;16:875-8. 8. Tagami H, Watanabe S, Ofugi S, Minami K. Trichophyton contact sensitivity in patients with dermatophytosis. Arch Dermatol 1977;113:1409-14. 9. Edman B. Palmar eczema: a pathogenetic role for acetylsalicylic acid, contraceptives and smoking? Acta Derm Venereol 1988; 68:402-7. 10. Rosen K, Mobacken H, Swanbeck G. Chronic eczematous dermatitis of the hands: a comparison of PUVA and UVB treatment. Acta Derm Venereol 1987;67:48-54. 11. Tegner E, Thelin I. PUVA treatment of chronic eczematous dermatitis of the palms and soles. Acta Derm Venereol 1985;65: 451-3. 12. Anonide A, Usiglio D, Pestarina A, Massone L. Droxicam photosensitivity with dyshidrotic hand dermatitis. Int J Dermatol 1997;36:318-20. 13. McKerrow K, Greig DE. Piroxicam-induced photosensitive dermatitis. J Am Acad Dermatol 1986;15:1237-41.
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14. Braunstein BL. Dyshidrotic eczema associated with piroxicam photosensitivity. Cutis 1985;35:485-6. 15. Youn JI, Lee HG, Yeo UC, Lee YS. Piroxicam photosensitivity associated with vesicular hand dermatitis. Clin Exp Dermatol 1993; 18:52-4. 16. Gona´lez E, Gona´lez S. Drug photosensitivity, idiopathic photodermatoses, and sunscreens. J Am Acad Dermatol 1996;35:87185. 17. Allen H, Kaidbey K. Persistent photosensitivity following occupational exposure to epoxy resin. Arch Dermatol 1979;115: 1307-10. 18. Burry JN. Persistent light reaction from buclosamide. Arch Dermatol 1970;101:95-7.
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19. Burry JN. Photoallergies to fenticlor and Multifungin. Arch Dermatol 1967;95:287-91. 20. Frain-Bell W. The idiopathic photodermatoses. Cutaneous photobiology. Oxford: Oxford University Press; 1985. p. 24-59. 21. Hood AF, Elpern DJ, Morison WL. Histopathologic findings in papulovesicular light eruption. J Cutan Pathol 1986;13:13-21. 22. Weedon D. Vesiculobullous reaction pattern. In: Skin pathology. Edinburgh: Churchill Livingstone; 1997. p. 133. 23. Weedon D. Pompholyx. In: Skin pathology. Edinburgh: Churchill Livingstone; 1997. p. 95. 24. Dawe RS, Russell S, Ferguson J. Borrowing from museums and industry: two photoprotective devices. Br J Dermatol 1996;135: 1016-7.