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Photodermatoses in Children

Photodermatoses in Children

Review article

Photodermatoses in children

Siti Nurani Fauziah, Wresti Indriatmi, Lili Legiawati

Department of Dermatology & Venereology Faculty of Medicine, Universitas Indonesia, dr. Cipto Mangunkusumo Hospital, Jakarta, Indonesia

E-mail: [email protected]

Abstract

Photodermatoses cover the ’s abnormal reactions to sunlight, usually to its (UV) component or visible light. Etiologically, photodermatoses can be classified into 4 categories: (1) immunologically mediated photodermatoses (idiopathic photodermatoses); (2) drug- or chemical-induced photosensitivity; (3) hereditary photodermatoses; and (4) photoaggravated dermatoses. The incidence of photodermatoses in the pediatric population is much lower than in adults. Polymorphous light eruption (PMLE) is the most common form of photodermatoses in children, followed by erythropoietic protoporphyria. Early diagnosis and investigations should be performed to avoid long-term complications. Photoprotection is the mainstay of photodermatoses management, including use of physical protection and sunscreen.

Keywords: children, photodermatoses, photoprotection, polymorphous light eruption.

Background usually on the face, neck, extensor forearms, and hands. Early recognition of symptoms and early Photodermatoses is a term used to describe diagnosis is important to prevent complications 1 abnormal reactions of the skin to light, especially due to inadequate photoprotection. to ultraviolet (UV) radiation or visible light.1-3 Incidence of photodermatoses in children is lower This paper will explore the more commonly compared to in adults. Jansen reported 82% out encountered photodermatoses: immunologically- of 95 children with photodermatoses were mediated and drug- or chemical-induced diagnosed with polymorphous light eruption photodermatoses. (PMLE).4 Studies conducted by Horkay et al. and Ten Berge et al. found similar results, where Classification PMLE is the most commonly found Photodermatoses in children comprise several in children.5,6 Photodermatoses groups of diseases, and the classifications induced by systemic or topical agents are rare in available are made to assist clinical evaluation of children, but the number of cases has been photobiological processes.1,3 According to their increasing in the last few years due to the rise in etiology, photodermatoses in children can be photosensitizer use.1 classified as:1 1. Immunologically-mediated According to the data on patient visits in the photodermatoses pediatric dermatology outpatient clinic in dr. Cipto - Polymorphous light eruption (PMLE) Mangunkusumo General Hospital (CMGH), - Juvenile spring eruption (JSE) Jakarta, Indonesia, in the 2014-2015 period there - Actinic prurigo (AP) was 1 patient with endogenous chemical-induced - (SU) photodermatosis and 176 patients with - (HV) photoaggravated dermatoses, out of a total of 1150 patient visits.7 Photodermatoses can be 2. Drug- or chemical-induced suspected if reactions such as appear on a. Exogenous: the exposed areas shortly after sun exposure, Phototoxicity: systemic and topical

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Photoallergy: systemic and topical unclear, immune responses between b. Endogenous: cutaneous photoantigens and UV rays are thought to play a role.1,2 3. Hereditary Hereditary photodermatoses includes xeroderma 1. Polymorphous light eruption (PMLE) pigmentosum, Cockayne syndrome, PMLE can be found in children and adults, trichothiodystrophy, Rothmund-Thomson especially in young women. Horkay et al. reported syndrome, Bloom syndrome, Smith-Lemli-Opitz 4% of 398 PMLE cases has the age of onset under syndrome, Hartnup disease, and Kindler 5 years old, and 10% is between the age of 6-10.5 syndrome. In Finland, 25% of all PMLE cases appeared before the age of 15.4 PMLE is the most common 4. Photoaggravated photodermatosis in children.1,4-6 It is more often Photoadggravated photodermatoses includes found in Fitzpatrick type 1 skin.2 Family history of atopic dermatitis (AD), Darier-White disease, PMLE is positive in 3-56% cases.8 dermatitis herpetiformis, herpes simplex infection, lupus erythematosus (LE), dermatomyositis, PMLE is speculated to develop due to UV pellagra, psoriasis, and seborrheic dermatitis. irradiation on the skin’s photoantigens, leading to delayed hypersensitivity responses. The Diagnosis “hardening” phenomenon, where severe clinical Photodermatoses in children are diagnosed from manifestations are found on first exposure and history and physical findings. History includes age milder symptoms will develop on subsequent on onset, climate during eruption, duration exposures.1-3 between sun exposure and lesion onset, duration and evolution of skin lesions, exposure to Clinical manifestations photosensitizers (topical or systemic), Clinical signs of PMLE can be polymorphous, involvement of other organs or systemic which includes papules, papulovesicular involvement, and family history of eruptions, vesicobullous eruptions, plaques, photodermatoses and consanguinity.1 insect bite-like eruptions, urticaria, and lesions similar to erythema multiforme. Usually, PMLE Lesion distribution is a vital clinical feature in eruptions present as confluent erythematous children with suspected photodermatoses; lesions papules forming symmetrical plaques on the face. generally appear in sun-exposed areas, such as Subjective symptoms can include mild pruritus the face, the neck (V area), dorsal forearms, and and a burning sensation. Lesions develop 30 hands. Locations that are relatively lesion-free minutes to 48 hours after sun exposure, and fade also need to be examined, which are the upper in several days. Systemic symptoms are rarely eyelid, behind the ears (Wilkinson triangle), found, but cases with fever, headache, and submental, nasolabial folds, and neck folds. nausea have been reported.1,8-9 Lesion morphology can vary during: 1) the acute phase, which consists of vesicles, papules, Differential diagnosis excoriations, and crusts; 2) the chronic phase Differential diagnosis of PMLE in children include which consists of lichenification. Furthermore, AD, LE, SU, HV, and erythropoietic protoporphyria other forms of skin lesions can be observed in (EPP).1 specific diseases, such as urticaria in solar urticaria, acute phase of erythropoietic Investigations protoporphyria (EPP), and atrophic scars in HV.1 Histopathology Workup includes laboratory examination, skin Edema, focal spongiosis, and vesicles can be biopsy, and phototests. Evaluation of growth and found in the epidermis. Moreover, acanthosis, development, systemic involvement, and focal parakeratosis, and basal vacuolization can neurological deficits are important to help identify be present. Perivascular infiltrate of lymphocytes specific genodermatosis related to (dominant), neutrophils, and eosinophils can be photodermatoses.1 seen.1,2

Immunologically-Mediated Photodermatoses Phototesting Immunologically-mediated photodermatoses, The minimal erythema doses (MEDs) to UVA and previously known as idiopathic photodermatoses UVB in most PMLE patients are normal. or primary photodermatoses, comprise PMLE, Provocative phototesting can be performed to JSE, SU, HV, and AP. The pathophysiology is confirm diagnosis by irradiating the skin with UVA

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or UVB, beginning with twice the MEDs, continued JSE management. Oral antihistamines can be with 20-40% dosage increase per day for 3-4 given to manage pruritus, if present.1 days, and the exposed area is observed for 1-2 days for PMLE lesions.1 Phototesting is only 3. Actinic prurigo (AP) useful to differentiate PMLE from other similar AP is most frequently found in Mexico, Central and clinical diseases, because PMLE’s clinical South America, especially in individuals living at manifestations are nonspecific.3 altitudes over 1.000 m above sea level, but cases in Asia and in Caucasians have also been Management reported. The human leukocyte antigen (HLA) is The most effective approach to managing PMLE involved in AP; the subtype HLADRB1*0407 is the is to avoid sun exposure. Topical corticosteroids most prevalent, found in 60-70% of cases. are effective when lesions are newly developed. Generally AP develops in children younger than Systemic corticosteroids can be administered to 10 years old, but can be found in people aged 2- patients with severe and acute PMLE, usually 43 years.14,15 prednisone 0.6-1 mg/kg body weight/day, tapered down according to clinical improvement.10 In Clinical manifestations patients with recurrent PMLE, prophylactic Clinical findings of AP can include highly pruritic phototherapy with narrowband UVB (NB UVB) or papules, plaques, and nodules, together with psoralen with UVA (PUVA) with similar dosing to excoriations and scars in sun exposed areas such phototherapy for psoriasis, three times a week for as the face, neck, extensor forearms, and dorsal 5 weeks, can be considered.9 Other treatments surfaces of the hands. Eczematous lesions and such as antimalaria agents, betacarotene, and lichenification can be seen. Exacerbations usually nicotinamide can help manage PMLE, but their happen during the summer and the spring. The mechanisms of action are unclear.1 lips and conjunctiva may be involved, presenting as cheilitis, conjunctivitis, and pseudopterigium. 2. Juvenile spring eruption (JSE) Cases of alopecia of the eyebrows related to AP Studies of children in New Zealand reported the have been reported. Spontaneous remission is prevalence of JSE was 6.7%, and the most possible, although childhood-onset AP is commonly affected area is the top of the ears generally persistent.16,17 which is not covered by hair. JSE occurs more often in boys, aged 5-23 years.11 Differential diagnosis Differential diagnosis of AP in children include Pathogenesis PMLE and other photodermatoses, such as HV, The etiopathogenesis of JSE is unclear, but it is EPP, LE, and AD.1 thought to be similar to PMLE.1 Investigations Clinical manifestations Histopathology JSE is regarded as a localized form of PMLE. Skin biopsy shows a non-specific subacute Eruptions usually happen in the spring, presenting dermatitis or chronic dermatitis, thickening of the as erythematous papules in the helix of the ears, basement membrane, and lymphocyte infiltrates which evolve to vesicles and crusts, and resolve in the dermis.18 without scarring.1 Phototest Study in Australia showed a decrease in the Differential diagnosis minimum erythema dose (MED) in 60% of cases Differential diagnosis of JSE are acute eczema, with abnormal results against the UVA spectrum herpes of the helix, and erythema multiforme.12 in 100% of cases.13 In contrast, studies by Hojyo- Tomoka in Mexico showed an abnormal response Investigations to light provocation tests with UVA and UVB, and Histopathology normal MED against UVA and UVB.16 Apoptotic cells, mild spongiosis, and vesicles may be found in the epidermis, and mononuclear Management infiltrates are found in the dermis.13 Sun protection, including sunglasses and protective lip balm, is the main pillar of AP Management management. Topical corticosteroids, emollients, Protection against sun exposure, topical and oral antihistamines can be used to relieve corticosteroids, and emollients are effective for pruritus. Administration of antimalaria agents, betacarotene, vitamin E, and pentoxyphillin is of

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unclear efficacy.1 Phototherapy with NB-UVB and Management PUVA can help prevent formation of new lesions The main component of HV management is sun in some patients.17 Currently, thalidomide is the protection. Effective treatment is not yet available. most effective treatment for patients with AP, with Chloroquines, betacarotene, and PUVA are found a starting dose of 50-100 mg/day, continued with to be effective in several cases. In severe cases, a maintenance dose of 50 mg/week. Possible systemic corticosteroids may be administered.1 adverse effects include teratogenic effects and peripheral neuropathy, which are rarely found in 5. Solar urticaria (SU) children.16 SU is an uncommon form of photodermatoses. Age of onset for SU widely varies, ranging from 4. Hydroa vacciniforme (HV) the age of one week to old age. SU mostly This type of photodermatosis is rare, and is usually develops in early adulthood.23,24 only found in children. Generally, the age of onset is 8 years old, and will resolve in early adulthood. Clinical manifestations HV is more frequently found in boys.19,20 SU lesions are characterized by urticaria Pathogenesis of HV is unclear, it is thought to be surrounded by erythematous areas, with pruritus related to latent Epstein-Barr virus (EBV) and burning sensations. Lesions are usually infections.21 located in the exposed area, but lesions can Clinical manifestations develop all over the body. Reaction time ranges Lesions in HV start as 2-3 mm erythematous from a few seconds to 10 minutes after exposure, macules which will develop into vesicles, and can resolve within 24 hours. Systemic appearing within a few hours to 2 days after symptoms such as headache, nausea, shortness exposure. The lesions resolve in several days with of breath, and syncope can be found.21 crusting and atrophic scars similar to scars of variola (varioliform).1 Pathogenesis The mechanism underlying the development of Differential diagnosis SU is an immediate type hypersensitivity reaction, Differential diagnosis of HV in children are other mediated by immunoglobulin E (IgE). blistering photodermatoses, namely EPP, Photoallergens are thought to be produced by the vesicular PMLE, bullous LE, and PCT.22 skin as a response to electromagnetic radiation. SU can be induced by a spectrum of varying HV lesions develop in sun exposed areas, wavelengths, but is usually a reaction to UVA and especially the face and the dorsal surface of the visible light irradiation. The photoallergens will be hands. Eruptions are common in the summer. recognized by their specific IgE on the surface of Symptoms can be preceded by pruritus and a mast cells, causing degranulation and the release burning sensation, a few hours before lesions of histamines and other mediator cells.25 appear. Eyes and lips involvement can cause keratoconjunctivitis, uveitis, and blistering of the Differential diagnosis lips. Pediatric patients with photodermatoses, Differential diagnosis of SU in children include especially HV, experience adverse effects on PMLE, EPP, and other photodermatoses induced quality of life.20 by drugs or chemicals.1

Investigations Investigations Histopathology Phototesting as a provocative test aims to In early lesions of HV, vesicles are found in the investigate the action spectrum and the minimal epidermis; infiltrates, hemorrhages, and urticarial dose needed to induce SU.21 thrombosis are seen in the dermis. In fully developed lesions, necrosis in the epidermis and Management dermis with mononuclear cell infiltrates are Photoprotection is the main treatment for SU; observed.1 there are currently no available specific treatments for SU. To relieve symptoms, topical Phototesting corticosteroids or oral antihistamines can be In monochromatic phototesting, most patients given.25 NB UVB phototherapy can be performed, reveal sensitivity to UVA radiation, which may starting from a low dose, increased slowly.26 Other cause papulovesicular lesions.19 treatments, such as betacarotene, antimalaria agents, plasmapheresis, immunosuppressive agents, and intravenous immunoglobulins have

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been reported as effective for adult patients, but fluoroquinolone), griseofulvin, sulfonylurea, these treatments should be used with caution in furosemide, nonsteroidal antiinflammatory agents, children.1 amiodarone, isoniazid, and thiazides.1

Calzavara-Pinton et al. studied 29 patients divided The principle of treatment is to identify and avoid into two groups, group A who were not sensitive to the culprit phototoxins. Photoprotection is UVB and group B who were sensitive to UVB. Both achieved through sun avoidance and use of groups were irradiated with NB UVB. Group A sunscreens. In acute phototoxicity, compresses received a cumulative dose of NB UVB of 10,3 and topical corticosteroids can be applied. In J/cm2 and Group B received 9,1 J/cm2. In follow up severe cases, systemic corticosteroids can be visits after 3 months, sun tolerance increased in used.1-3 both groups, with SU relapse in 6 patients in group A and 2 patients in group B.26 2. Photoallergic reactions Photoallergic reactions are changes in skin Drug- Or Exogenous Chemical-Induced reactivity through delayed-type hypersensitivity, Photodermatoses which needs sensitizers in the form of photoallergens and exposure to light of a certain Drug- or chemical-induced photodermatoses due wavelength, especially UVA. The mechanism of to exogenous sensitizers, both topical and photoallergic reactions starts with absorption of systemic, are rarely found in children; they are radiation by photoallergens, producing haptens more frequently found in adults. Based on their that will merge with carrier proteins to create pathophysiology, the dermatoses are divided into antigens and induce immune responses. phototoxic reactions and photoallergic Photoallergic reactions are rarely found in reactions.1,27 children.2,3

1. Phototoxic reactions Eczematous eruptions develop in 24-48 hours Phototoxic reactions do not depend on immune after exposure, distributed mainly in the sun- responses. These reactions develop in individuals exposed area, accompanied with subjective who are exposed to certain amounts of sensitizers symptoms of pruritus.1,2 Several substances have or phototoxins on a certain wavelength. The been reported to provoke photoallergic reactions, primary light involved is UVA.1-3 Several factors such as octocrylene, benzophenone-3, and influence the severity of phototoxicity, such as: methoxydibenzoylmethane which can be found in dose of phototoxins, topical absorption of sunscreens.1 phototoxins, pharmacokinetics of systemic phototoxins, and the penetration of action Photoallergic reactions can be managed by firstly spectrum radiation.3 The incidence of phototoxic identifying and avoiding the culprit photoallergen reactions is unknown. Phytophotodermatosis are and any substances that may cross-react with it, the most common phototoxic reaction in children. avoiding sun exposure, and use of sunscreens.1-3

Phytophotodermatosis is a form of phototoxic Based on the accumulation of precursor in reaction associated with exposure to UVA the organs, the porphyrias can be divided into radiation and furocoumarin, a phototoxin found in hepatic and erythropoietic. Moreover, the plants. Furocoumarin can be found in lemons, porphyrias can also be classified according to their limes, carrots, parsnips, parsley, celery, meadow clinical manifestations: acute , grass, giant hogweed, dill, figs, wheat, clover, cutaneous porphyria, and recessive porphyria.28 buttercups, and spinach.1,3 Onset of lesions occur within one day after exposure to UV radiation and is a potent photosensitizer which furocoumarin. Clinical manifestations can vary causes photosensitivity in CP, with major action from mild erythema to blisters, evolving to spectrums ranging from 400-405 nm (the Sorbet hyperpigmentations. Lesions are characterized by band), and 600-650 nm (visible red light).30 linear hyperpigmentations on the face, chest, hands, and lower limbs. Hyperpigmentations Clinical manifestations of CP varies, a burning appear in one to two weeks, and persist for 6 to 12 sensation might be felt, in addition to edema, months.1 blisters, and scars, due to the differences in water Medications frequently causing phototoxic solubility of porphyrin precursors. The degree of reactions in children are antibiotics (doxycycline, water solubility is highest in uroporphyrinogen, tetracyclines, sulfonamides, nalidixic acid, and followed by coproporphyrinogen, then

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protoporphyrinogen. Childhood-onset CP include Clinical manifestations congenital (CEP), Symptoms of PPE generally appears between the erythropoietic protoporphyria (EPP), porphyria age of 1-6, with an average age of onset of 4 years cutanea tarda (PCT), hepatoerythropoietic old. Clinical findings include erythema and edema, porphyria (HEP), hereditary coproporphyria accompanied with a stinging or burning sensation (HCP), and variegate porphyria (VP).1 on the face, dorsal surfaces of the hands and feet, which develops within several minutes of sun 1. Erythropoietic protoporphyria (EPP) exposure. Ecchymosis, vesicles, and crusts can PPE is the most common form of porphyria in appear and persist for several days. Repeated children.4-6 In PPE caused by ferrochelatase and intense sun exposure can lead to onycholysis, enzyme deficiency, clinical manifestations will hyperkeratosis of the knuckles, and scarring on develop when ferrochelatase activity is < 50%. the nose. Systemic involvement in the form of EPP is an autosomal dominant hereditary microcytic hypochromic anemia, cholelithiasis, disorder. Biochemically, this defect causes and liver dysfunction may be seen.1,31 protophyrin accumulation especially in the erythrocytes. In addition, accumulation is also Differential diagnosis found in the skin, liver, plasma, gallbladder, and Clinically, EPP is similar with phototoxic drug feces.1 reactions, hydroa vacciniforme, solar urticarial, contact dermatitis and angioedema or other types of cutaneous porphyria.32

Table 1. Differences between phototoxic and photoallergic reactions.*

Phototoxic Photoallergic Clinical Manifestations - Occurrence after first exposure Yes No - Onset of eruption after exposure Several minutes to hours 24-48 hours - Dose needed for eruption to Large Small develop - Cross reactivity with other None Common substances - Clinical findings Sunburn reaction: erythema, Varies, generally pruritic edema, vesicles, and bullae; eczematous lesions stinging and burning sensation; resolves with hyperpigmentation - Distribution Exposed skin Exposed skin, may spread to other unexposed areas Histology Keratinocyte necrosis, Spongiosis dermatitis, epidermal necrosis, edema, lymphohistyocyte infiltrate in the lymphocyte infiltrate, dermis macrophage, and neutrophil in the dermis Pathophysiology Direct tissue damage Delayed type hypersensitivity reaction Diagnosis - Topical agent Clinical Photopatch test - Systemic agent Clinical and phototest Clinical, phototest, and photopatch test *Adapted and modified from reference no. 27

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ALA Succinyl ALA synthetase dehydratase CoA ALA PBG + Glycine PBG deaminase

Hydroxymethybilane CP III oxidase Protoporphyrinogen IX CEP URO III synthase PP III oxidase PV HCP Uroporphyrinogen III Uroporphyrinogen I Protoporphyrin IX PCT/HEP URO decarboxylase Ferrochelatase EPP Coproporphyrinogen III Coproporphyrinogen I 2+ Fe Heme

Mitochondria Globin chains Cytoplasm

Figure 1. Heme biosynthesis and enzymatic defects in cutaneous porphyria.1 (Quoted with modification from reference number 1) *CEP=Congenital erythropoietic porphyria; PCT=; HEP=Hepatoerythropoietic porphyria; EPP=Erythropoietic protoporphyria; HCP=Hereditary coproporphyria; VP=Variegate porphyria; ALA= Aminolevulinic acid; CP III oxidase= coproporphyrinogen oxidase; PBG=porphobilinogen; PP III oxidase=protoporphyrinogen oxidase; URO decarboxylase=uroporphyrinogen decarboxylase; URO III synthetase=uroporphyrinogen III synthase

Investigations children. PCT is caused by heterozygous Laboratory findings may include elevated levels of deficiency in uroporphyrinogen decarboxylase porphyrin in the erythrocytes, plasma, bone (UroD), while HEP is caused by homozygous UroD marrow, and feces. Peripheral smear under deficiency. PCT has an estimated incidence of a fluorescence microscope may reveal 1:25,000.1 There are three types of PCT: (1) PCT fluorescence of erythrocytes. Fluorescence of the type I (sporadic), which is an adult-onset acquired nails and teeth is not observed. Plasma disorder with a decrease of UroD activity in the fluorescence emission spectroscopy shows a peak liver; (2) PCT type II (familial), which is an at 634 mm.28 autosomal dominant hereditary disorder with a decrease of UroD activity in all tissues; (3) PCT Management type III (familial), which is also an autosomal Avoidance of direct sunlight and sunscreen use is dominant hereditary disorder with a decrease of done for photoprotection. Administration of 30-150 UroD activity in the liver.34 mgs of beta carotene in children may be considered. Moreover, cholestyramine 4 g/day can Clinical manifestation be given to inhibit absorption of protoporphyrin, and Cutaneous lesions in PCT appear in the form of 15 mg/kg/day of chenodeoxycholic acid can be erosions, vesicles, or bullaes in sun-exposed given to inhibit production of protoporphyrin in the areas, especially on the dorsal surfaces of the liver.1,33 forearms and hands. Lesion size varies from 1 mm to 3 cm. Lesions resolve with hyperpigmentation, 2. Porphyria cutanea tarda (PCT) and formation of milia, or scarring. In addition, hepatoerythropoietic porphyria (HEP) periorbital hypertrichosis, onycholysis, and PCT is the most common form of porphyria in sclerodermoid skin changes can appear in non adults, and the second most common form in sun-exposed areas. Complications rarely occur, J Gen Proced Dermatol Venereol Indones. 2017;2(2):77-88 83

but ocular pain, photophobia, and scleral mutilation of acral tissues. Furthermore, perforation have been reported. Clinical hypertrichosis of the face and extremities may be manifestations of HEP are similar, though more found, along with hyperpigmentation and alopecia. severe than PCT. In PHE, findings may include Ocular and bony involvements include sclerodermoid lesions, hypertrichosis, photophobia, corneal scarring, ulcers, erythrodema, anemia (especially hemolytic), and keratoconjunctivitis, cataracts, and fractures.1,38 hepatosplenomegaly.1,35 Differential diagnosis Differential diagnosis CEP in children can be mistaken as other The symptoms of PCT and HEP are similar to VP, porphyrias, photosensitivity in early infancy such as HCP and CEP. Clinically, PCT could also be xeroderma pigmentosum, Bloom syndrome, mistaken as photoxic drug reactions or skin lesions Kindler syndrome, Cockayne syndrome, and associated with hemodialysis in which porphyrin Smith-Lemli-Opitz syndrome.36 metabolism occur to be in normal level. PCT should be differentiated from other bullous dermatoses, Investigations such as bullous pemphigoid, epidermolysis Laboratory examinations reveal an increase of bullosa, pemphigus, and dermatitis herpetiformis.36 uroporphyrin I and coproporphyrin I levels in erythrocytes, bone marrow, plasma, urine, and Investigations feces. Blood studies show normocytic and Laboratory investigations show an increase of normochromic anemia with an increase of uroporphyrin levels and 7-carboxyl porphyrin in reticulocytes. Exposing urine, teeth, and fecal plasma and urine, and isocoproporphyrin in feces. suspensions to Wood’s lamp can reveal red Porphyrin levels in erythrocytes are normal. fluorescence.1 Fluoresence emission spectroscopy of plasma shows a peak at 620 nm. Skin biopsy reveals Management subepidermal bullae, and periodic acid-Schiff The recommended treatment is sun avoidance staining reveals precipitation around blood using sunglasses, protective clothing, and vessels.1 sunscreen which contains titanium dioxide or zinc oxide. Beta carotene is reported to be effective due Management to its photoprotective effects. Blood transfusions Sun avoidance is fundamental for photoprotection, and splenectomy can be performed to manage and sunscreen use is important to prevent hemolytic anemia. Bone marrow and stem cell symptoms. Low dose hydroxychloroquine (3 mg/kg transplant can be considered. The prognosis of body weight) may be given twice a week. CEP is poor, death frequently occurs and is Phlebotomy may be considered for patients who do associated with hemolytic anemia.1,37,39 not respond to chloroquines. Spontaneous remission can occur with advancing age. In 5-16% 4. Hereditary coproporphyria (HCP) of adult patients with untreated disease, HCP is a disorder caused by coproporphyrinogen can occur.1 oxydase deficiency. HCP is an inherited autosomal dominant disorder. HCP is generally described in 3. Congenital erythropoietic porphyria (CEP) adults, and rarely found in children.40 The CEP, also known as Gunther’s disease, is an provoking factors of HCP include phenobarbital autosomal recessive hereditary disorder. CEP has use, estrogen, progesteron, pregnancy, and the most severe clinical symptoms out of the menstruation.1 porphyrias.37 CEP is caused by the deficiency of uroporphyrinogen synthase, which leads to Clinical manifestation accumulation of uroporphyrinogen I and Neurovisceral symptoms such as abdominal pain, coproporphyrinogen I isomers.28 , and are frequently found in HCP. Cutaneous lesions are observed in 20-30% of patients, the lesions are similar to lesions of Clinical manifestations PCT.1 CEP is characterized by dark colored urine, severe photosensitivity which occurs around the age of 2- Differential diagnosis 3, splenomegaly, dark colored teeth, and hemolytic HCP presents with acute neurovisceral symptoms, anemia. Cutaneous lesions in CEP patients include therefore mimicking acute intermittent porphyria vesicles and bullaes filled with fluid that fluoresces (AIP), VP and δ–aminolevulinic aciduria (ALAD).41 pink, and can evolve to ulcerations, scarring, and

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Investigations 2. Vandergriff WT, Bergstresser PR. Abnormal Workup reveals an increase in coproporphyrin III responses to ultraviolet radiation: Idiophatic, levels in plasma, urine, and feses.1 probably immunologic, and photoexacerbated. In: Goldsmith LA, Katz SL, Gilchrest BA, Paller Management AS, Leffell DJ, Wolff K, editors. Fitzpatrick’s Identification and avoidance of provoking factors, dermatology in general medicine. 8th ed. New especially medications, is fundamental. Sun York: McGraw-Hill; 2012.p.1049-65. avoidance, use of protective clothing, sunscreen 3. Soebaryo RW. Fotosensitivitas. In: Menaldi use, and use of hemin preparations. If symptoms SL, Bramono K, Indriatmi W, editor. Ilmu such as abdominal pain, nausea, and vomiting penyakit kulit dan kelamin. 7th edition. Jakarta: occur, symptomatic medications can be given.1,42 Badan Penerbit FKUI; 2015.p.206-12. 4. Jansen CT. Photosensitivity in childhood. Acta 5. Variegate porphyria (VP) Derm Venereol Suppl.1981;95:54-7. VP is an autosomal dominant disorder, caused by 5. Horkay I, Emri G, Varga V, Simics E, Remenyik the decreased activity of protoporphyrinogen E. Photosensitivity skin disorders in childhood. oxidase. The onset of VP is after puberty, generally Photodermatol Photoimmunol Photomed. in the fourth decade of life. VP is rarely found in 2008;24:56-60. 43 children. 6. Ten Berge O, Sigurdsson V, Bruijnzeel- Koomen CA, van Weelden H, Pasmans SG. Clinical manifestations Photosensitivity testing in children. J Am Acad Neurovisceral clinical features include nausea, Dermatol. 2010;63:1019-25. vomiting, abdominal pain, and constipation. 7. Data on patient’s visit in the pediatric Cutaneous lesions appear in 60% of adult patients, dermatology outpatient clinic, dr. Cipto with lesions similar to PCT but less severe.28 Mangunkusumo General Hospital (CMGH)

from 2014-2015. Differential diagnosis VP should be differentiated from HCP, AIP, 8. Stratigos AJ, Antoniou C, Katsambas AD. ALAD.41 Polymorphous light eruption. J Eur Acad Dermatol Venereol. 2002;16:193-206. Investigations 9. Honigsmann H. Polymorphous light eruption. Laboratory studies show an increase of 4-carboxyl Photodermatol Photoimmunol Photomed. and 5-carboxyl in the urine. Plasma 2008;24:155-61. fluorescence emission spectroscopy reveals a 10. Patel DC, Bellaney GJ, Seed PT, McGregor peak at 624-627 nm.1 JM, Hawk JL. Efficacy of short-course oral prednisolone in polymorphic light eruption: A Management randomized controlled trial. Br J Dermatol. Treatment for VP is similar to HCP, consists of sun 2000;143: 828-31. avoidance and provoking factors, especially 11. Tan E, Eberhart-Phillips J, Sharples K. medications.1 Juvenile spring eruption: A prevalence study. N Z Med J 1996;109:293-5. Conclusions 12. Anderson D, Wallace J, Howes EIB. Juvenile spring eruptions. Lancet. 1954:263:755-6. Photodermatoses are rarely found in children. 13. 0Stratigos AJ, Antoniou C, Papadakis P, PMLE is the most commonly found form of Papapostolou A, Sabatziotis D, Tranaka K, et photodermatoses in children. Recognition of early al. Juvenile spring eruption: Clinicopathologic symptoms and early diagnosis are important to features and phototesting results in 4 cases. J prevent long term complications, such as Am Acad Dermatol. 2004;50:Suppl 2:S57-60. malignancy. Photoprotection through sun 14. Crouch R, Foley P, Baker C. Actinic prurigo: A avoidance, physical protection, and sunscreen use retrospective analysis of 21 cases referred to are the main pillars of photodermatoses. an Australian photobiology clinic. Australas J Dermatol. 2002;43:128-32. References 15. Grabczynska SA, McGregor JM, Kondeatis E, Vaughan RW, Hawk JL. Actinic prurigo and 1. Chantorn R, Lim HW, Shwayder TA. polymorphic light eruption: Common Photosensitivity disorders in children. Part I. J pathogenesis and the importance of HLA- Am Acad Dermatol. 2012;67:1093-110. DR4/DRB1*0407. Br J Dermatol. 1999;140:232-6.

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16. Hojyo-Tomoka MT, Vega-Memije ME, Cortes- 30. Asawanonda P, Oberlender S, Taylor C. The Franco R, Dominguez- Soto L. Diagnosis and use of dihydroxyacetone for photoprotection in treatment of actinic prurigo. Dermatol Ther. variegate porphyria. Int J Dermatol. 2003;16:40-4. 1999;38:916-8. 17. Ross G, Foley P, Baker C. Actinic prurigo. Photodermatol Photoimmunol Photomed. 31. Murphy GM. Diagnosis and management of 2008;24:272-5 the erythropoietic porphyrias. Dermatol Ther. 18. Vega-Memije ME, Mosqueda-Taylor A, 2003;16:57-64. Irigoyen-Camacho ME, Hojyo-Tomoka MT, 32. Thunell S, Harper P, Brun A: Porphyrins, Dominguez-Soto L. Actinic prurigo cheilitis: porphyrin metabolism and porphyrias. IV. Clinicopathologic analysis and therapeutic Pathophysiology of erythyropoietic results in 116 cases. Oral Surg Oral Med Oral protoporphyria--diagnosis, care and Pathol Oral Radiol Endod. 2002;94:83-91. 19. Gupta G, Man I, Kemmett D. Hydroa monitoring of the patient. Scand J Clin Lab vacciniforme: A clinical and follow-up study of Invest. 2000,60:581-604. 17 cases. J Am Acad Dermatol. 2000;42:208- 33. Minder EI, Schneider-Yin X, Steurer J, 13. Bachmann LM. A systematic review of 20. Huggins RH, Leithauser LA, Eide MJ, Hexsel treatment options for dermal photosensitivity in CL, Jacobsen G, Lim HW. Quality of life erythropoietic protoporphyria. Cell Mol Biol. assessment and disease experience of patient 2009;55:84-97. members of a web-based hydroa vacciniforme support group. Photodermatol Photoimmunol 34. Mendez M, Poblete-Gutierrez P, Garcia-Bravo Photomed. 2009;25:209-15. M, Wiederholt T, Moran-Jimenez MJ, Merk HF, 21. Botto NC, Warshaw EM. Solar urticaria. J Am et al. Molecular heterogeneity of familial Acad Dermatol. 2008;59:909-20. porphyria cutanea tarda in Spain: 22. Iwatsuki K, Satoh M, Yamamoto T, Oono T, Characterization of 10 novel in the Morizane S, Ohtsuka M, et al. Pathogenic link UROD . Br J Dermatol. 2007;157:501-7. between hydroa vacciniforme and 35. Altiparmak UE, Oflu Y, Kocaoglu FA, EpsteineBarr viruse associated hematologic disorders. Arch Dermatol. 2006;142:587-95. Katircioglu YA, Duman S. Ocular complications 23. Harris A, Burge SM, George SA. Solar urticaria in 2 cases with porphyria. Cornea. in an infant. Br J Dermatol. 1997;136:105-7. 2008;27:1093-6. 24. Beattie PE, Dawe RS, Ibbotson SH, Ferguson 36. Schulenburg-Brand D, Katugampola R, J. Characteristics and prognosis of idiopathic Badminton MN. The cutaneous porphyrias. solar urticaria: a cohort of 87 cases. Arch Dermatol Clin. 2014;32:369-84. Dermatol. 2003;139:1149-54. 37. Harada FA, Shwayder TA, Desnick RJ, Lim 25. Beissert S, Stander H, Schwarz T. UVA rush hardening for the treatment of solar urticaria. J HW. Treatment of severe congenital Am Acad Dermatol. 2000;42: 1030-2. erythropoietic porphyria by bone marrow 26. Calzavara-Pinton P, Zane C, Rossi M, Sala R, transplantation. J Am Acad Dermatol. Venturini M. Narrowband ultraviolet B 2001;45:279-82. phototherapy is a suitable treatment option for 38. Huang JL, Zaider E, Roth P, Garcia O, Pollack solar urticaria. J Am Acad Dermatol. S, Poh-Fitzpatrick MB. Congenital 2012;67:e5-9. erythropoietic porphyria: Clinical, 27. Lim HW. Abnormal responses to ultraviolet radiation: Photosensitivity induced by biochemeeical, and enzymatic profile of a exogenous agents. In: Goldsmith LA, Katz SL, severely affected infant. J Am Acad Dermatol. Gilchrest BA, Paller AS, Leffell DJ, Wolff K, 1996;34:924-7. editors. Fitzpatrick’s dermatology in general 39. Shaw PH, Mancini AJ, McConnell JP, Brown medicine. 8th ed. New York: McGraw-Hill; D, Kletzel M. Treatment of congenital 2012.p.1066-74. erythropoietic porphyria in children by 28. Puy H, Gouya L, Deybach JC. Porphyrias. allogeneic stem cell transplantation: A case Lancet. 2010;375:924-37. 29. Pietrangelo A. The porphyrias: report and review of the literature. Bone pathophysiology. Intern Emerg Med. Marrow Transplant. 2001;27:101-5. 2010;5:Suppl 1:S65-71.

J Gen Proced Dermatol Venereol Indones. 2017;2(2):77-88 86

40. Jeanmougin M, Pedreiro J, Manciet JR, Moulin 42. Siegesmund M, van Tuyll van Serooskerken JP, Civatte J. Hydroa vacciniforme type AM, Poblete-Gutierrez P, Frank J. The acute eruption disclosing hereditary coproporphyria hepatic porphyrias: current status and future challenges. Best Pract Res Clin Gastroenterol. [in French]. Ann Dermatol Venereol. 2010;24:593-605. 1988;115:1236-8. 43. Mustajoki P, Tenhunen R, Niemi KM, 41. Bissell DM. The Porphyrias. In: Rosenberg RN, Nordmann Y, Kaariainen H, Norio R. Pascual JM. Rosenberg’s molecular and Homozygous variegate porphyria. A severe genetic basis of neurological and psychiatric skin disease of infancy. Clin Genet th disease. 5 ed. New York: Elsevier; 1987;32:300-5. 2015.p.731-49.

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Approach To Diagnose Photodermatoses In Children

TandaSigns anddan atausymptoms gejala setalahafter UV terpajan exposure sinar matahari

History Riwayatof photosensitizer pajanan dengan exposure

photosensitizer FototoksikPhototoxic atau or YesYa photoallergicfotoalergi No Tidak

HistoryRiwayat of previous terdapat skin penyakit diseases kulit sebelumnya

YesYa Photoaggravated TidakNo Photoaggravated

Systemic/Keterlibatan organs sistemik/organ, involvement, seperti such as:: gangguan impaired growth,tumbuh intellectual, kembang, andintelektual, eye development dan mata

Hereditary Ya Fotodermatosis Yes photodermatoses TidakNo herediter Ye s PemeriksaanPlasma porphyrin porfirin plasma test

Negatif Positif Negative Positive

FotodermatosisImmunologically yang- PorfiriaCutaneous kutan diperantaraimediated sistem porphyria photodermatosesimun

***Quoted with modifications from reference number 1

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