Hydroa Vacciniforme



Hydroa vacciniforme (HV) is a rare, chronic photodermatosis of unknown origin occurring in childhood that exists within the spectrum of Epstein-Barr virus–related lymphoproliferative disorders. These range from classic HV to fatal lymphoma.[1]

Recurrent vesicles on sun-exposed skin that heal with vacciniform or varioliform scarring characterize HV. The histopathologic features are distinctive and demonstrate intraepidermal reticular degeneration and cellular necrosis.[2] Most cases remit spontaneously by late adolescence.[3] See the image below.

View Image

Characteristic vesicular lesions occur on sun-exposed skin and heal with varioliform scarring.


The etiology of hydroa vacciniforme (HV) is uncertain. HV may be a distinct entity distinguished by scarring or may occur within the spectrum of polymorphous light eruption. Skin lesions occur on sun-exposed skin, such as the face, ears, and hands. There is an association between HV occurrence and latent Epstein-Barr virus (EBV) infection, particularly if necrotic lesions are present.[4] T cells positive for EBV-encoded small nuclear RNA (EBER) have been detected in the cutaneous infiltrates of some patients with HV. Ultraviolet-induced cutaneous lesions with histopathology consistent with HV have also been shown to contain EBER-positive cells.[5] In general, the EBV DNA blood load is higher in patients with HV than in patients with other photosensitivity disorders.[6]


The development of hydroa vacciniforme (HV) lesions and their distribution suggest a causal relationship between HV and ultraviolet (UV) exposure, although the pathogenetic mechanism remains unknown.[7] Ultraviolet A (UV-A) radiation is most often implicated. Two reports of HV in siblings have been documented, suggesting a genetic component to HV.[8] Some cases have occurred in the setting of hematopoietic malignancy. Moreover, HV can be caused by a recent or latent EBV infection.[5]



The frequency of HV varies according to country but is estimated to be around 0.34 case per 100,000 people.


Males have a higher incidence of HV than females. Males who are affected may also have a longer course of disease than females.[9]


HV predominately affects children aged 3-15 years.[2] The mean duration from onset of symptoms to its resolution is nine years. Resolution of symptoms typically occurs in adolescence or young adulthood, although symptoms persist throughout life in some patients.[9] Cases of HV in infants and elderly persons have also been described.[10]


The prognosis is uncertain; classic hydroa vacciniforme (HV) typically remits by adolescence. No mortality is associated with classic HV, but those with lymphoid atypia, rimming of lipocytes, and Amerindian heritage are at significant risk of progression and death. Classic chemotherapy is associated with adverse outcomes.[11]

Patient Education

Patients are advised regarding strict sun avoidance, frequent application of high SPF sunscreens with UV-A blocking agents, and protective clothing.


Commonly, mild burning, itching, or stinging in exposed sites begins a few hours or days after sun exposure. Vesicles heal with varioliform scarring.[4] The initial onset of lesions occurs in spring, with recurrences in summer months.

Constitutional symptoms can occur but are uncommon. Oral and ocular symptoms can occur but are extremely rare.

Physical Examination

Skin and mucous membranes[12] are the primary sites affected by hydroa vacciniforme (HV). Ocular involvement is uncommon and usually occurs along with an HV outbreak of the face.[13]

Skin findings are as follows:

Eye findings are as follows[13, 4] :

Other symptoms are as follows:

Severe HV may present with the following[16] :


Complications are rare in hydroa vacciniforme (HV). The most common severe sequela is the varioliform scarring.

Laboratory Studies

See the list below:

Imaging Studies

Imaging studies are not routinely obtained as part of the workup of hydroa vacciniforme (HV).

Other Tests

Repetitive, broad-spectrum, UV-A phototesting may be warranted. Repetitive, broad-spectrum, low-dose UV-A irradiation can elicit lesions clinically and histologically identical to those produced by natural UV exposure, although results are inconsistent. The minimal erythemal dose of UV-B and UV-A in these patients is reduced.[28]

Histologic Findings

Early lesions reveal an epidermal, multilocular vesicle with reticular degeneration and demonstrate EBV RNA (EBER positive) in lymphocytes.[29]  A dense, perivascular, lymphohistiocytic infiltrate with vessel hemorrhage may occur in the dermis. Late lesions show epidermal and dermal necrosis with a surrounding, chronic, inflammatory infiltrate. Direct immunofluorescence study results are usually normal, except for rare reports (2 patients) of C3 deposits at the dermoepidermal junction and in the small dermal vessels.

Medical Care

In addition to medication and certain restrictions on activity, management of hydroa vacciniforme (HV) may include a prophylactic "hardening" course of phototherapy. In a study of four patients with HV, low-dose, narrow-band UV-B (TL-01) phototherapy, either daily or 3 times a week in the spring, was shown to confer relative photoprotection.[30] Psoralen photochemotherapy (PUVA) administered prophylactically in older patients may be effective in desensitization. After intercalating with DNA and irradiation by UV-A, methoxsalen leads to formation of DNA psoralen adducts that cross-link DNA.[31]


Consult a dermatologist for evaluation and management of hydroa vacciniforme (HV). 


Generally, no diet restrictions or requirements are indicated in the management of hydroa vacciniforme (HV).


Strict sun avoidance, appropriate clothing, and frequent application of high sun protection factor (SPF) sunscreens with UV-A blocking agents are advised.

Rigid sun avoidance may be socially devastating for the pediatric patient with hydroa vacciniforme (HV). The physician should work closely with the parents and management team in supporting and educating the child regarding this disease.


Avoiding the sun, frequently applying high SPF sunscreens with UV-A blocking agents, and wearing protective clothing may prevent episodes of hydroa vacciniforme (HV).

Long-Term Monitoring

Patients with extracutaneous findings associated with hydroa vacciniforme (HV) should be referred to the appropriate specialist.

Medication Summary

To date, no oral therapy reliably prevents the appearance of hydroa vacciniforme (HV) lesions. Oral antimalarials[32] and beta-carotene[33, 34, 35] may be used and are occasionally reported to be useful, especially when combined with a strict sun avoidance program. Other therapies that have been used with varying success include thalidomide, azathioprine, cyclosporine,[36] and fish oil supplementation.[37, 38, 39] Given the association with EBV, there may be some benefit to the use of antivirals such as acyclovir and valacyclovir.[4]

Hydroxychloroquine (Plaquenil)

Clinical Context:  Hydroxychloroquine can be used for the suppression of lesions in sun-sensitive disorders; its mechanism of action in HV is unknown.

Chloroquine (Aralen)

Clinical Context:  Chloroquine has anti-inflammatory activity by suppressing lymphocyte transformation and may have a photoprotective effect. It can be used for the suppression of lesions; its mechanism of action in HV is unknown.

Class Summary

These agents suppress cutaneous lesions associated with many photodermatoses.

Beta-carotene (Lumitene, B-Caro-T, A-Caro-25)

Clinical Context:  Beta-carotene's mechanism of action is not completely elucidated but it may relate to the ability of carotenoids to quench photoexcited molecular species. It reduces the severity of photosensitivity reactions in some patients with photodermatoses, especially erythropoietic protoporphyria (EPP).

Class Summary

These agents are yellow-orange pigments that may have photoprotective properties in selected photodermatoses.

Methoxsalen (8-MOP, Oxsoralen)

Clinical Context:  Methoxsalen inhibits mitosis by binding covalently to pyrimidine bases in DNA when photoactivated by UV-A.

Class Summary

After intercalating with DNA and irradiation by UV-A, methoxsalen leads to formation of DNA psoralen adducts that cross-link DNA. This affects gene expression by inhibiting DNA replication, mitosis, and cell division. 5-Methoxypsoralen (5-MOP, Bergapten, Psoraderm 5) has also been used, although it is not currently available in the United States.

Acyclovir (Zovirax)

Clinical Context:  Acyclovir is a synthetic purine nucleoside analogue with activity against a number of herpesviruses, including herpes simplex and varicella-zoster. It is highly selective for virus-infected cells because of its high affinity for viral thymidine kinase enzyme. This effect serves to concentrate acyclovir monophosphate into virus-infected cells. The monophosphate then is metabolized into the triphosphate active form by cellular kinases.

Valacyclovir (Valtrex)

Clinical Context:  Valacyclovir is a prodrug rapidly converted to the active drug acyclovir. It is more expensive but has a more convenient dosing regimen than acyclovir.

Class Summary

Given the association with EBV, there may be some benefit to the use of antivirals such as acyclovir and valacyclovir.

What is hydroa vacciniforme (HV)?What is the pathophysiology of hydroa vacciniforme (HV)?What causes hydroa vacciniforme (HV)?What is the prevalence of hydroa vacciniforme (HV)?What are the sexual predilections of hydroa vacciniforme (HV)?Which age groups have the highest prevalence of hydroa vacciniforme (HV)?What is the prognosis of hydroa vacciniforme (HV)?What is included in patient education about hydroa vacciniforme (HV)?Which clinical history findings are characteristic of hydroa vacciniforme (HV)?What sites in the body are primarily affected by hydroa vacciniforme (HV)?Which skin findings are characteristic of hydroa vacciniforme (HV)?Which ocular findings are characteristic of hydroa vacciniforme (HV)?What are the less common signs and symptoms of hydroa vacciniforme (HV)?What are the signs and symptoms of severe hydroa vacciniforme (HV)?What are the possible complications of hydroa vacciniforme (HV)?Which conditions are included in the differential diagnoses of hydroa vacciniforme (HV)?What are the differential diagnoses for Hydroa Vacciniforme?Which lab tests are performed in the workup of hydroa vacciniforme (HV)?What is the role of imaging studies in the workup of hydroa vacciniforme (HV)?What is the role of phototesting in the workup of hydroa vacciniforme (HV)?Which histologic findings are characteristic of hydroa vacciniforme (HV)?How is hydroa vacciniforme (HV) treated?Which specialist consultations are beneficial to patients with hydroa vacciniforme (HV)?Which dietary modification are used in the treatment of treatment of hydroa vacciniforme (HV)?Which activity modification are used in the treatment of treatment of hydroa vacciniforme (HV)?How is hydroa vacciniforme (HV) prevented?What is included in the long-term monitoring of hydroa vacciniforme (HV)?What is the role of medications in the treatment of hydroa vacciniforme (HV)?Which medications in the drug class Antivirals, Other are used in the treatment of Hydroa Vacciniforme?Which medications in the drug class Psoralens are used in the treatment of Hydroa Vacciniforme?Which medications in the drug class Carotenoids are used in the treatment of Hydroa Vacciniforme?Which medications in the drug class Antimalarials are used in the treatment of Hydroa Vacciniforme?


Gregory Toy, State University of New York Downstate College of Medicine

Disclosure: Nothing to disclose.


Jeannette Rachel Jakus, MD, MBA, Clinical Assistant Professor, Director of Clinical Research, Assistant Program Director, Department of Dermatology, SUNY Downstate Medical Center; Dermatologist, Brody Dermatology

Disclosure: Nothing to disclose.

Marjon Vatanchi, MD, Assistant Professor, Director of Nail Surgery and Special Procedures, Department of Dermatology, The Warren Alpert Medical School of Brown University

Disclosure: Nothing to disclose.

Specialty Editors

Michael J Wells, MD, FAAD, Dermatologic/Mohs Surgeon, The Surgery Center at Plano Dermatology

Disclosure: Nothing to disclose.

Van Perry, MD, Assistant Professor, Department of Medicine, Division of Dermatology, University of Texas School of Medicine at San Antonio

Disclosure: Nothing to disclose.

Chief Editor

Dirk M Elston, MD, Professor and Chairman, Department of Dermatology and Dermatologic Surgery, Medical University of South Carolina College of Medicine

Disclosure: Nothing to disclose.

Additional Contributors

Maureen B Poh-Fitzpatrick, MD, Professor Emerita of Dermatology and Special Lecturer, Columbia University College of Physicians and Surgeons

Disclosure: Nothing to disclose.

Quynh L Sebastian, MD, Clinical Instructor, Division of Dermatology, UCLA David Geffen School of Medicine

Disclosure: Nothing to disclose.

Raul Del Rosario, MD, Consulting Staff, Dermatopathology, Mission Hospital at Laguna Beach

Disclosure: Nothing to disclose.


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Characteristic vesicular lesions occur on sun-exposed skin and heal with varioliform scarring.

Characteristic vesicular lesions occur on sun-exposed skin and heal with varioliform scarring.