5

Click here to load reader

Photosensitivity skin disorders in childhood

Embed Size (px)

Citation preview

Page 1: Photosensitivity skin disorders in childhood

R E V I E W A R T I C L E

Photosensitivity skin disorders in childhoodIrene Horkay, Gabriella Emri, Viktoria Varga, Eniko Simics & Eva Remenyik

Department of Dermatology, University of Debrecen, Debrecen, Hungary

Key words:clinical features; diagnosis;

photodermatoses; treatment

Correspondence:Irene Horkay, M.D., Ph.D., Department of

Dermatology, University of Debrecen, Nagyerdei krt.

98, H-4032 Debrecen, Hungary.

Tel: 136 52 432282

Fax: 136 52 414632

e-mail: [email protected]

Accepted for publication:5 December 2007

Conflicts of interest:None declared.

Summary

Photosensitivity in childhood is caused by a diverse group of diseases. It usually indicates

idiopathic photodermatoses, first of all polymorphic light eruption. It may be an early

symptom of genetic disorders such as porphyria or very rare genophotodermatoses.

Photosensitivity secondary to topical or systemic external agents as well as photoexacerbated

dermatoses is not so frequent in childhood. Here we present our experience with childhood

photosensitivity skin diseases collected over a 40-year period.

L ight-induced skin eruptions are not a common problem in

pediatric dermatology. However, the condition often causes

trouble and discomfort to the affected child and the parents.

The literature on childhood photodermatoses (PDs) is

relatively scanty. The incidence of PDs in childhood is much

lower than in adults (1). According to the paper published by

Jansen (2), photosensitivity started at the age of 15 years or

earlier in 26% of the cases out of a total of 370 PD patients. There

is also a shortage of primary data on the prevalence of PDs

classified recently by Yashar and Lim (3) such as (i) idiopathic

PD: polymorphic light eruption (PLE), juvenile spring eruption

of the ears (JSE), solar urticaria (SU), hydroa vacciniforme (HV),

(ii) photosensitivity secondary to exogenous agents, (iii)

cutaneous porphyrias, (iv) genophotodermatoses and (v)

photoexacerbated/aggravated disorders. The paper presents

experience with PDs in childhood (83 cases) collected at the

Department of Dermatology, Debrecen, between 1967 and 2006.

The diagnosis in the vast majority of PD cases in children is

PLE, whereas the order of other diseases is quite variable

depending on geographic and genetic conditions. In the Finnish

report (2) mentioned before, PLE was followed by xeroderma

pigmentosum (XP) and then erythropoietic protoporphyria

(EPP), while no cases were recorded from external

photosensitizers. According to other literary data, phototoxic

dermatitis occurs relatively often besides idiopathic PDs during

childhood (4). Similar to these findings the most frequent

diagnosis at our Department of Dermatology was also PLE.

However, we recorded a rather high number of EPP cases and

some porphyria cutanea tarda (PCT) as well, but only a few cases

of XP (Table 1).

Diagnosis of PD in childhood is not as easy as in adulthood (5).

In the history occasionally (mostly in EPP) a family history is noted,

such as in our patient material (6). The clinical picture is featured by

various kinds of eruptions localized typically on the sun-exposed

skin. The diagnosis in childhood can also be confirmed by phototests.

Most informative is the provocation test used to reproduce lesions

of idiopathic PDs (5). We perform it with ultraviolet (UV)B and

UVA separately (Multitester SBB LT 400; Saalmann, Herford,

Germany) (7) according to the protocol of Lehmann et al. (8).

Photopatch testing for identifying external photosensitizer(s) is

not performed commonly in children. We have not used it in

our practice. Concerning laboratory tests, in porphyrias spectro-

fluorimetric scanning of plasma porphyrins is recommended for

screening, followed by a quantitative assay to determine the

intermediates in the RBCs and the urine. Immunoserology and

occasionally immunofluorescence of skin lesions are used to

distinguish idiopathic PDs and lupus erythematosus (LE).

Chromosomal analysis, measurement of unscheduled DNA

synthesis (9), amino acid levels in the urine and detailed genetic

study are valuable methods applied in genophotodermatoses.

r 2008 The Authors

Journal compilation r 2008 Blackwell Munksgaard � Photodermatology, Photoimmunology & Photomedicine 24, 56–6056

Page 2: Photosensitivity skin disorders in childhood

Idiopathic photodermatoses

In the idiopathic group of PDs the most frequent disorder in

childhood is also PLE, in which an abnormal immune response

to sunlight due to the impaired immunoregulatory mechanism

was recently detected (10) and a strong genetic background was

suggested (11).

Family history has been reported for 14–52% of subjects in some

series (12, 13). The variability in the literary data is partly due to

nosological problems, namely, whether actinic prurigo (AP), also

called hydroa aestivale, is a variant of PLE or a distinct entity (14).

Several authors (2, 15, 16), including Hungarians, consider AP

to be a variant of PLE. Recent genetic studies (17) support the

view that AP possibly represents an HLA-restricted subset of PLE.

In addition, some authors, also the Hungarians, claim that JSE

represents a distinct entity (18) rather than a variant of PLE (19).

In our material (38 children), a family history of PLE including

AP/hydroa aestivale was detected in three cases (brother and

sister, daughter, mother and grandmother, respectively).

Although the age of onset in PLE ranges from childhood to late

adult life, it is not rare that light sensitivity starts before

adolescence. In Scottish studies, 20% of the cases occurred

before 10 years of age (20) and 47% before 20 years of age

(14), whereas in Finland (2) about 25% of the cases developed

earlier than 15 years of age. In our material (398 PLE patients

between 1967 and 2006), 4% of the cases manifested before 5

years of age and 10% between 6 and 14 years before adolescence

(21).

Concerning clinical features, the itchy eruptions are polymorphic

but are mostly monomorphous in any child. The distribution of

the clinical types in different patient cohorts varies due to

geographic conditions and genetic factors including skin

phototypes. The most common type is the papular form in

general, whereas in the Scandinavian countries (2) the prurigo-

like eruptions are predominant. In Hungary mostly small

erythematous papules (�75%) (Fig. 1a), not so frequently

papulovesicles, eczematous (�20%), rarely pruriginous

eruptions (�5%, i.e. one child) and never plaque-like lesions

are seen in childhood. In 70% of our material, provocative

phototesting confirming the diagnosis is positive in the vast

majority of children (8). The action spectrum of our cases proved

to be mostly UVB, whereas in a German cohort it was UVA in

80% of children (4). Reproduced lesions developed within 1

week: in the eczematous type after the second or third irradiation

and in the papular type after the fourth to sixth irradiation

(Fig. 1b) (22). Immunoserology, which is always mandatory in

PLE, was negative in all our cases.

The treatment of lesions is symptomatic (topical steroids,

antihistamines). Effective prophylaxis can be achieved in the

majority of children – including our patients – by mechanical

photoprotection and regular use of broad-spectrum sunscreens

containing mainly physical blockers such as micronized TiO2. In

some cases, preseasonal ‘light hardening’ with a low dose of UVB

(23) or UVA (24) is helpful in preventing recurrence. We have

also had good experience with it in adulthood, but rarely in

children (25).

In JSE, a typical childhood PD, the eruptions occur every

spring till adolescence and heal spontaneously without scar

formation (5). We have recorded seven cases over the last 40

years. All of them were 10–12-year-old boys, whose typical skin

lesions, i.e. papules and vesicles in a characteristic localization on

the ears, disappeared after puberty. Till that time topical

sunscreens and suitable coiffure were recommended.

SU induced by a wide spectrum of wavelengths (280 nm to

the visible irradiation) is a rather rare idiopathic PD manifested

occasionally in childhood (26, 27). Photosensitivity usually

persists over the entire lifetime. Preventing the recurrence is

rather difficult (24, 26). A unique familial SU case in a 2-year-old

Hungarian boy and his first-degree relatives of three generations

(age of the patients: 3–78 years) was presented at the Eighth

European Society for Pediatric Dermatology Congress in

Budapest, 2005 (28). The case is under publication.

The very rare HV Bazin classically arises in childhood and

tends to heal spontaneously during adolescence (24). Two cases,

one girl and one boy, were recorded at our department over the

last three decades (29). The skin lesions, itchy papules and

vesicles with surrounding erythema resolving with

characteristic vacciniforme scars manifested at the age of 3 and

6 years, respectively, and reoccurred year by year despite

prophylactic measurements with broad-spectrum sunscreens

and recommended oral b-carotene (24). The disorder of the girl

healed spontaneously after puberty, whereas the boy

unfortunately died because of an intercurrent disease at 9 years

of age. Recently most of the patients have been treated with

beneficial results using prophylactic narrow-band UVB

phototherapy (30).

Photosensitivity secondary to exogenous agents

In general, childhood photosensitization by external chemicals

or internal medication is rather rare (31). In the more common

phototoxic dermatitis with erythema, edema, and sometimes blisters,

the provoking agents in childhood are usually psoralen-

containing plants (phytophotodermatitis). All three cases

recorded at our department were typical phytophotodermatitis.

Pseudoporphyria caused by non-steroidal, anti-inflammatory

Table 1. Number of childhood-onset photodermatoses (PD) Debrecen/

Hungary, 1967–2006

Diagnosis

Polymorphic light eruption (PLE) 38

Juvenile spring eruption of the ears (JSE) 7

Solar urticaria 1Hydroa vacciniforme 2

Phototoxic contact dermatitis 3

Erythropoietic protoporphyria (EPP) 23

Porphyria cutanea tarda (PCT) 4Xeroderma pigmentosum (XP) 3

Systemic lupus erythematosus (SLE) 1

Pellagra 1

Total 83

57

r 2008 The Authors

Journal compilation r 2008 Blackwell Munksgaard � Photodermatology, Photoimmunology & Photomedicine 24, 56–60

Photosensitivity skin disorders

Page 3: Photosensitivity skin disorders in childhood

drugs such as naproxen (32) and drug-induced systemic

phototoxicity with widespread eruptions are not so frequent in

children (24). We have not observed such cases for the time

being. Neither have we recorded photoallergic dermatitis provoked by

chemicals (fragrances, sunscreens) or topically administered

drugs.

Cutaneous porphyrias

All forms of porphyria, the most common inherited cause of

photosensitivity (33), can arise in childhood. We mainly

diagnosed EPP and a few cases of PCT.

The most frequent childhood porphyria is EPP manifested in

early infancy, and usually transmitted in an autosomal dominant

manner. A heterogeneous group of mutations in the gene of

ferrochelatase has been detected (34). A novel mutation has been

revealed in one of our patients (35). Family history is rather

common. In our material, 17 cases from six families were

recorded; six other cases were sporadic (5). Immediate

photosensitivity manifests as a painful swelling with erythema,

urticaria or blisters (hydroa) healing with scars (Fig. 2a). The

majority of our patients represented hydroa-type EPP, whereas

others had swelling with a burning sensation or purpuric lesions.

With the progression of the disease, characteristic chronic skin

symptoms (waxy thickening of the sun-exposed skin and orange

peel appearance of the nose) (36) were observed (Fig. 2b). In

addition to the laboratory tests, routine histology and electron

microscopic examination of the liver of our young patients were

performed in 1967, which revealed mitochondrial alterations

and other ultrastructural changes suggesting the role of the liver

in the pathomechanism of EPP (37, 38). The prophylactic

possibilities include broad-spectrum sunscreens, oral b-carotene

with moderate effect (39), and recently narrow-band UVB

phototherapy (40). Gene therapy should become possible in the

future. b-Carotene administration (for 6 months yearly) offered

satisfactory prophylaxis for only the minority of our patients.

Serial phlebotomies (Ippen’s cure) (41) proved to be effective in

two other cases (5).

Fig. 1. Erythematous papules in

polymorphic light eruption (a),

positive provocation test (b).

Fig. 2. Hydroa-like lesions with scars

in erythropoietic protoporphyria (a),

orange peel nose (b).

r 2008 The Authors

Journal compilation r 2008 Blackwell Munksgaard � Photodermatology, Photoimmunology & Photomedicine 24, 56–6058

Horkay et al.

Page 4: Photosensitivity skin disorders in childhood

Hepatic porphyrias are not so frequent in childhood (42).

Familial PCT may arise in the first decade of life, similar to its

extremely rare homozygous form called hepatoerythropoietic

porphyria (43). In our material, four PCT patients out of about

300 cases were diagnosed before adolescence: one sporadic (a 7-

year-old boy) and a familial case (one sister and two brothers)

(44). In the latter unique cases cooperative genetic studies in

Barcelona revealed an uncommon compound heterozygotic

combination of a novel and another, previously reported

mutation in the UROD gene. The paper has been accepted for

publication (45). A therapeutically low dose of chloroquine,

recommended intermittently in childhood, was administered

with success in all four cases.

Genophotodermatoses

Genophotodermatoses (31, 39) with different kinds of genetic

defects in the UV repair processes (XP, Cockayne’s syndrome,

trichothiodystrophy, etc.) or with other biochemical

abnormalities (Smith–Lemli–Opitz syndrome, Hartnup disease,

etc.) are very rare inherited disorders. Besides the characteristic

skin symptoms, these disorders are usually associated with an

early development of cutaneous and ocular malignancies as well

as specific extracutaneous features. We recorded three XP patients

between 1967 and 2006 (Fig. 3), two young boys (aged 3 and 5

years) and one girl (aged 7 years) (46) with photosensitivity and

large pigmented freckles present from 2, 3 and 2 years of age,

respectively. One of the boys died within 3 years due to

widespread cutaneous and ocular malignancies, the other

committed suicide during adolescence. The girl was taken home

by the desperate parents just after diagnosing XP and never

appeared again. Repair of the UV-induced DNA damage in

peripheral lymphocytes (46) and keratinocytes of patients (9)

was studied by autoradiographic and liquid scintillation

techniques (47). XP cells showed a highly reduced unscheduled

DNA synthesis, similar to the literary data (48). Tumor

prophylaxis with local sunscreens and systemic retinoids was

ineffective in our cases.

Photoexacerbated/aggravated disorders

The diverse groups of photoexacerbated/aggravated disorders

(LE, dermatomyositis, erythema multiforme, atopic dermatitis,

pellagra, psoriasis, etc.) with different kinds of pathogenesis are

not real PDs, and are not common in childhood. We recorded

one case with pellagra and another with systemic lupus

erythematosus over the last four decades.

In conclusion, photosensitivity disorders in childhood include

a wide range of conditions. Some of them are more frequent in

the pediatric population than in adulthood whereas others heal

spontaneously during adolescence and vice versa. Prompt

recognition of photosensitivity permits early diagnosis and may

circumvent some of the later complications associated with these

diseases. Effective photoprotection is crucial (4, 49).

References

1. Inamadar AC, Palit A. Photosensitivity in children: an approach

to diagnosis and management. Indian J Dermatol Venereol Leprol 2005;

71: 73–79.

2. Jansen CT. Photosensitivity in childhood. Acta Derm-venereol 1981;

95 (Suppl.): 54–57.

3. Yashar SS, Lim HW. Classification and evaluation of photoder-

matoses. Dermatol Ther 2003; 16: 1–7.

4. Neumann NJ, Lehmann P. Lichtdermatosen in Kindesalter.

Hautarzt 2003; 54: 25–32.

5. Roelandts R. The diagnosis of photosensitivity. Arch Dermatol

2000; 136: 1152–1157.

6. Horkay I, Kosa A. Protoporphyria erythropoetica (in Hungar-

ian). B}orgyogy Vener Szle 1992; 68: 155–161.

7. Horkay I, Kosa A, Simics E. Diagnostic phototesting in dermatol-

ogy. Acta Derm Vener Alp Pann Adr 1996; 5: 67–68.

8. Lehmann P, Fritsch C, Neumannn NJ. Photodiagnostische Test-

verfahren. Teil 2 Hautarzt 2000; 51: 449–459.

9. Horkay I, Varga L, Tamasi P, Gundy S. Repair of DNA damage in

light sensitive human skin diseases. Arch Dermatol Res 1978; 263:

307–315.

10. Palmer RA, Friedmann PS. Ultraviolet radiation causes less

immunosuppression in patients with polymorphic light erup-

tion. J Invest Dermatol 2004; 122: 291.

11. McGregor JM, Grabczynska SA, Vaughan RW, Hawk JLM, Lewis

CM. Genetic modeling of abnormal photosensitivity in families

with polymorphic light eruption and actinic prurigo. J Invest

Dermatol 2000; 115: 471–476.

12. Frain-Bell W, McKenzie LA, Witham E. Chronic polymorphic light

eruption: a study of 25 cases. Br J Dermatol 1969; 81: 885–896.

13. Jansen CT. Heredity of chronic polymorphous light eruptions.

Arch Dermatol 1978; 114: 188–190.

14. Ferguson J. Polymorphic light eruption and actinic prurigo. Curr

Probl Dermatol 1990; 2: 127–147.

15. Dominguez L, Hojyo MT. Actinic prurigo, a variety of poly-

morphous light eruption. Int J Dermatol 1982; 21: 260–261.

16. Epstein JH. Polymorphous light eruption. J Am Acad Dermatol

1980; 3: 329–333.

17. Grabczynska SA, McGregor JM, Kondeatis E, Vaughan RW, Hawk

JLM. Actinic prurigo and polymorphic light eruption: common

pathogenesis and importance of HLA-DR4/DBR1�0407. Br J

Dermatol 1999; 140: 232–236.

Fig. 3. Xeroderma pigmentosum with a malignant skin tumor in early

childhood.

59

r 2008 The Authors

Journal compilation r 2008 Blackwell Munksgaard � Photodermatology, Photoimmunology & Photomedicine 24, 56–60

Photosensitivity skin disorders

Page 5: Photosensitivity skin disorders in childhood

18. Requena L, Algre V, Hasson A. Spring eruption of the ears. Int J

Dermatol 1990; 29: 284–286.

19. Berth-Jones J, Norris PG, Graham-Brown RAC, et al. Juvenile

spring eruption of the ears: a probable variant of polymorphic

light eruption. Br J Dermatol 1991; 124: 375–378.

20. Frain-Bell W. The idiopathic photodermatoses. In: Frain-Bell W,

ed. Cutaneous photobiology. Oxford: Oxford Univ. Press, 1985; 51–55.

21. Horkay I. The pathogenesis of polymorphic light eruption. Ph D

thesis (in Hungarian) Debrecen, 1979.

22. Horkay I, Bodolay E, Krajczar J, Alfoldi G. In situ identification of

T lymphocytes in polymorphic light eruption. Photodermatology

1984; 1: 250–252.

23. Jury C, McHenry P, Burden AD, Lever R, Bilsland D. Narrowband

ultraviolet B (UVB) phototherapy in children. Clin Exp Dermatol

2006; 31: 196–199.

24. Ott H, Baron JM. Nichthereditare Photodermatosen im Kinde-

salter. Hautarzt 2006; 57: 1059–1066.

25. Horkay I, Bodolay E, Kosa A. Immunological aspects of prophy-

lactic UVB and PUVA therapy in polymorphic light eruption.

Photodermatology 1986; 3: 47–49.

26. Harris A, Burge SM, George SA. Solar urticaria in an infant. Br J

Dermatol 1997; 136: 105–107.

27. Williams-Arya P, Hogan MB, Wilson NW. Solar urticaria in a 6-

year old child. Ann Allergy Asthma Immunol 1996; 76: 141–143.

28. Emri G, Bakos N, Remenyik E, Horkay I. A case of familial

photosensitivity manifested in childhood. Eur J Pediatr Dermatol

Book abstr 2005; L 08 04: 17–18.

29. Simics E, Szabo I, Hunyadi J, Horkay I. Hydroa vacciniformia

(Bazin). Prakt Dermatol 1998; 4: 10–12.

30. Gupta G, Man I, Kemmet D. Hydroa vacciniforme: a clinical and

follow-up study of 17 cases. J Am Acad Dermatol 2000; 42: 208–213.

31. Garzon MC, DeLeo VA. Photosensitivity in the pediatric patient.

Curr Op Pediatr 1997; 9: 377–387.

32. Schad S, Kraus A, Haubitz I, Trcka J, Hamm H, Girschick H. Early

onset pauciarticular arthritis is the major risk factor for naprox-

en-induced pseudoporphyria in juvenile idiopathic arthritis.

Arthritis Res Ther 2007; 9: R10.

33. Jensen JD, Resnick SD. Porphyria in childhood. Seminars Dermatol

1995; 14: 33–39.

34. Bloomer J, Wang Y, Singhal A, Risheg H. Biochemical abnorm-

ality in erythropoietic protoporphyria: cause and consequences.

J Pediatr Gastroenterol Nutr 2006; 43 (Suppl. 1): S36–S40.

35. Remenyik E, Lanyon GW, Horkay I, et al. Erythropoietic proto-

porphyria: a new mutation responsible for exon skipping int he

human ferrochelatase gene. J Invest Dermatol 1998; 111: 540–541.

36. Holme S, Anstey A, Finlay A, Elder G, Badminton M. Erythro-

poietic protoporphyria in the U. K.: clinical features and effect

on quality of life. Br J Dermatol 2006; 155: 574–581.

37. Horkay I, Balogh E, Vitalis S. Protoporphyria erythropoetica.

Zschr Haut-Geschl Krkh 1968; 43: 639–643.

38. Horkay I, Dan S, Lapis K, Jako J, Devenyi I. Damage to liver

mitochondria in erythropoietic protoporphyria. Haematologia

1969; 3: 195–204.

39. Poblete-Gutierrez P, Burgdorf WHC, Has C, Berneburg M, Frank

J. Hereditare photodermatosen. Hautarzt 2006; 57: 1067–1082.

40. Collins P, Ferguson J. Narrow-band UVB (TL-01) phototherapy:

an effective preventive treatment for the photodermatoses. Br J

Dermatol 1995; 132: 956–963.

41. Goerz G, Ippen H. Aderlassbehandlung der protoporphyrina-

mischen Lichtdermatose. Z Hautkr 1969; 44: 517–519.

42. Elder GH. Hepatic porphyrias in children. J Inher Metab Dis 1997;

20: 237–246.

43. Lim HW, Poh-Fitzpatrick MB. Hepatoerythropoietic porphyria, a

variant of childhood-onset porphyria cutanea tarda. J Am Acad

Dermatol 1984; 111: 1103–1111.

44. Horkay I, Emri G, Varga V, Koszo F. Familial porphyria cutanea

tarda in childhood. EADV ninth Congress, Geneve, 2000

abstract.

45. Remenyik E, Lecha M, Badenas C, et al. Childhood onset mild

cutaneous porphyria with compound heterozygotic mutations

in uroporphyrinogen decarboxylase gene. J Exp Clin Dermatol.

(in press).

46. Horkay I, Torok E, Tamasi P. Study on the pathomechanism and

therapy of xeroderma pigmentosum (in Hungarian). B}orgyogy

Vener Szle 1974; 50: 71–75.

47. Horkay I, Varga L, Altmann H, Kosa A. DNA repair and

photosensitivity in dermatology. In: Douglas RH, Moan J, Ronto

Gy, eds. Light in biology and medicine; Vol. 2. New York: Plenum

Press, 1991; 327–336.

48. Moriwaki SI, Kraemer KH. Xeroderma pigmentosum – bridging

a gap between clinic and laboratory. Photodermatol Photoimmunol

Photomed 2001; 17: 47–54.

49. Puech-Plottowa I, Michel J. Photodermatosis and photoprotec-

tion in children. Arch Pediatr 2000; 7: 668–679.

r 2008 The Authors

Journal compilation r 2008 Blackwell Munksgaard � Photodermatology, Photoimmunology & Photomedicine 24, 56–6060

Horkay et al.