HIV photodermatitis with widespread vitiligo-like depigmentation is rarely reported. We reported a photodistributed lichenoid drug eruption with depigmentation in an HIV-infected man on treatment for a second episode of tuberculosis. The rash initially developed during the first course of tuberculosis treatment and resulted in areas of depigmentation and hyperpigmentation. On reexposure to the same regimen to treat the second episode of tuberculosis, there was recurrence with violaceous patches within the depigmented areas from the first episode. On completion of the second regimen, repigmentation was considerably better than after the first episode. Phillips et al. reported a 60-year-old man ART naive man with advanced HIV (CD4 count of 7 cells/microl) who presented with a photodistributed, pruritic eruption associated with extensive depigmentation surrounded by hyperpigmentation. Histology revealed a spongiotic dermatitis with abundant eosinophils. A similar case was described involving a Ugandan woman with advanced HIV (CD4 count of 2 cells/microl) occurring one month after initiation of ART with stavudine, lamivudine, and nevirapine. Most areas repigmented after the regimen was changed to zidovudine, lamivudine, and efavirenz. The authors postulated that the photodistributed depigmentation was due to a photosensitizing effect of either the ART or cotrimoxazole; with the ART being more likely. Histology was not reported. All three cases were of Fitzpatrick skin phototype V or greater.
Depigmentation has also been reported in chronic lichenoid photo eruptions in HIV patients with a low CD4 T-lymphocyte count <50 cells/microl. We reported an HIV-infected man with low CD4 count and multidrug-resistant tuberculosis developed a generalised lichenoid eruption that progressively worsened and depigmented after initiating tuberculosis treatment. Treatment was continued under the cover of sun protection, potent topical corticosteroids, and PUVA to induce hardening. He completed nine months of treatment and soon afterwards the depigmentation reversed gradually.
Photosensitivity with depigmentation prior to the diagnosis of HIV, has also been reported. The presentation was marked by scaling, erythema, and concurrent vitiligo-like depigmentation of the face, arms, and hands. The condition improved with the use of sunscreen and topical steroids.
The differential diagnosis of photodermatitis with vitiligo-like depigmentation includes discoid lupus erythematosus (DLE), vitiligo, and lichen simplex chronicus. To differentiate from DLE there is an absence of scarring and histology does not demonstrate an interface dermatitis. The immunodeficiency, photo distribution, and histology demonstrating spongiotic dermatitis with eosinophils distinguish HIV photodermatitis from vitiligo. Likewise, the photo distribution and absence of lichenification exclude lichen simplex chronicus.
Actinic lichen planus is a morphologic variant of LP that predominantly affects sun-exposed areas and has a high prevalence in darker skin. Three variants of actinic LP have been described, namely annular, pigmented, and dyschromic, in that order of their frequency. The annular variant presents as annular erythematous brownish patches or plaques with or without atrophy. The major feature of the pigmented variant is the presence of melasma-like pigmentation. Dyschromic-type actinic lichen planus presents as whitish pinhead-sized and coalescent papules. HIV seems to have a stronger association with photolichenoid eruptions. In a series of 32 patients with histologically confirmed lichenoid eruption or photodermatitis, 12/32 were HIV infected, and in all 12, the lesions were photodistributed.
Photosensitive drugs are chromophores that absorb photons and undergo chemical reactions. The chemical structure of the chromophore determines the wavelengths of radiation it absorbs, with most reactions being caused by UVA rather than UVB. Drug-induced photodermatoses in the setting of HIV include phototoxic, photoallergic, and photolichenoid reactions. Drugs most commonly associated with photosensitization include amiodarone; chlorpromazine; thiazide diuretics; tetracyclines; quinolones, particularly nalidixic acid; nonsteroidal anti-inflammatory drugs derived from propionic acid, voriconazole and vemurafenib, a B-Raf enzyme inhibitor used in the management of late-stage melanoma.
ART, antituberculosis drugs, sulphonamides, and antifungals, all drugs used to treat HIV and associated opportunistic infections, have at least one drug or a class of drugs that has been reported to be a photosensitizer. Efavirenz, an ART drug, has been reported to cause a photodistributed transient eruption. A small series of five cases in South Africa reported photodistributed annular plaques with an indurated erythematous edge as the most common presentation of the efavirenz reaction. Figures 3, 4 Histology findings were non-specific. Systemic features were mild and included a mild elevation in alanine and/or aspartate transaminases. Despite the continuation of efavirenz, the majority resolved. Cotrimoxazole has been implicated in vitro as a photosensitizer, and the sulfamethoxazole component is believed to be responsible. Dapsone photoallergic dermatitis has been described in case reports. Despite its use as an alternative to cotrimoxazole for Pneumocystis jirovecii prophylaxis, there are no reports of dapsone photoallergic dermatitis in African people or HIV patients.
Antifungals known to cause photosensitivity include voriconazole, itraconazole, ketoconazole, and griseofulvin. Itraconazole reactions include a sunburn-like reaction, most likely phototoxic with decreased MED and negative photopatch tests. Voriconazole photosensitivity includes sunburn-like erythema, hand hyperpigmentation, linear papulo-vesicular lesions, erythroderma, discoid lupus erythematosus, actinic cheilitis and pseudoporphyria. Most reactions occurred in patients receiving long-term immunotherapy, however, there is no data reported in the HIV infected population. There are reports of the development of squamous cell carcinoma and melanoma in voriconazole-induced sites of photosensitivity. Amongst the drugs used to treat tuberculosis, photodistributed eczematous eruption due to isoniazid and pyrazinamide has been described. On discontinuing the drug, the photosensitivity usually resolves. However, persistent photosensitivity and progression to CAD have been reported.
Photolichenoid drug reactions seem to be more common in HIV-infected people than in the general population and in this setting often pose major management challenges. In a case series of 32 patients in San Francisco, with a histologic diagnosis of lichenoid eruption or photodermatitis, 12/32 were HIV infected, and all 12 were photodistributed. Exposure to known photosensitizing drugs preceded the eruption in 10/12. Patients with pigmented skin and advanced HIV disease (CD4 < 50 cells/microl), were disproportionately affected. Histologically 9/12 showed lichenoid reaction, 2/12 had features of lichen nitidus, and 1/12 was eczematous. Two of those with lichenoid reactions on histology developed marked depigmentation. No cases of lichen planus were found in the HIV-infected group. The authors suggested that previous cases of classic lichen planus in HIV may represent lichenoid photodermatitis.
Anti-tuberculosis medications, including isoniazid and pyrazinamide, have been reported to cause a lichenoid and/or photo lichenoid eruption. The pathogenesis is unclear but may be due to delayed hypersensitivity. LDR presents as purple itchy papules becoming confluent and hyperpigmented with continuing exposure to the offending drug. It is often photodistributed and lacks mucosal involvement Figures 5, 6. The interval between drug initiation and the rash ranges from days to years, with most cases occurring within months. On drug withdrawal, the lesions resolve with persistent hyperpigmentation, often lasting for many years. Although photolichenoid eruptions may be related to photosensitizing agents, there seems to be no association or changes in minimal erythemal dose. Photolichenoid reactions have been reported for isoniazid, confirmed by positive photopatch testing and oral rechallenge. Due to the lack of acute markers and delayed resolution of symptoms and signs of the reaction it is often difficult to identify the offending drug. Due to the relative urgency of treating tuberculosis in HIV and the limited number of effective safe drugs, all the drugs are sometimes continued with supportive care until completion of treatment in those with active tuberculosis.
Porphyria cutanea tarda (PCT), the most common form of porphyria, is caused by a deficiency of the fifth enzyme of the heme biosynthesis pathway, uroporphyrinogen decarboxylase (UROD). Decreased UROD activity leads to the overproduction of porphyrins in the liver. PCT is a cause of chemical-induced phototoxicity caused by sunlight interacting with endogenous porphyrins within the body. Clinically, these manifest in the third to fourth decade of life with photosensitivity, skin fragility, and blisters. The blisters occur in photodistributed sites particularly the face, V of the neck, and dorsa of the hands, and are associated with scarring and milia Figures 7, 8. Other features include hyperpigmentation, hypertrichosis, and rarely sclerodermoid changes. Earlier studies suggested a causal association between HIV and PCT. While the mechanism of PCT in HIV is still not fully understood, it is thought to be due to changes in porphyrin metabolism and liverinjury in the setting of co-infection with hepatitis C. It is now postulated that in most HIV-infected patients with PCT, hepatitis C and not HIV may induce a decrease in UROD activity. Drug exposure influences PCT. Amongst first-line antituberculosis drugs, rifampicin is the most likely to be associated with PCT. We recently encountered an HIV-infected man who presented with PCT after initiating rifampicin, isoniazid, pyrazinamide, and ethambutol. Based on published reports, we decided to replace rifampicin with rifabutin, a similarly effective rifamycin with less effect on the liver. The photosensitivity and blistering improved until he completed the remaining four months of his six-month course of treatment.
Diagnosis of PCT can be confirmed by histology and porphyrin levels. Histologically, PCT is characterized by a cell-poor subepidermal blister, festooning of the dermal papillae, and thickening and hyalinization of the dermal blood vessel walls. Additional features include caterpillar bodies and dermal sclerosis and a mild infiltrate of perivascular mononuclear cells in the upper dermis. These features are not specific to porphyria and can also occur in pseudoporphyria syndromes. The most important diagnostic test to diagnose porphyria remains porphyrin levels in serum, urine, and stool.
Pellagra, as mentioned earlier is a nutritional disease caused by the deficiency of niacin (also known as vitamin B3). Clinically pellagra is characterized by photodermatitis with gastrointestinal symptoms and neuropsychiatric ailments. Pellagra can be fatal if not timeously recognized and treated. Erythema is the initial clinical feature, and this evolves into hyperpigmentation, dryness, scale, lichenification, and fissuring. On the dorsum of the hands and forearms this is referred to as the gauntlet or glove sign. Asimilar feature on the lower extremities is called the boot sign. The development of fissures on the hands and feet surface is called goose skin. The eruption surrounding the base of the neck is called the Casal's collar or necklace Figure 9. In severe cases blistering occurs within the lesions and this is referred to as wet pellagra which tends to heal with scarring. Additionally, lesions may develop over bony prominences, perineum, and scrotum. The eruption usually presents as erosions with burning pain that intensifies on palpation. HIV as well as isoniazid, pyrazinamide, and ethionamide have been shown to cause pellagra or pellagra-like disease. It is thus even more important to recognize and prevent pellagra in HIV-infected people on treatment for tuberculosis, particularly breast-feeding women and young children. Breastfed infants receiving isoniazid should also receive pyridoxine 1 mg/kg daily.
There is a general consensus that chronic photosensitization is associated with an increase in the development skin cancer. This risk is determined by the Fitzpatrick skin type, age at which photosensitizer was used, duration and severity of photosensitization, immunosuppression, the photosensitizing agent/drug, and spectrum of UV absorption amongst others. Azathioprine, a photosensitizing immunosuppressant, used after solid organ transplant and inflammatory disorders is associated with an increased risk of squamous cell carcinoma (SCC) by additionally producing mutagenic reactive oxygen species on the skin and an additional risk of SCC on the skin. In transplant patients, the risk is estimated to be higher by the magnitude of 65-250 times. This is still applicable when comparing immunosuppressive regimens that incorporate azathioprine and those that do not. On the other hand, mycophenolate mofetil, a non-photosensitizing immunosuppressant of similar potency, reduces the incidence of SCC in this setting. Other photosensitizing drugs that have been associated with an increased risk of skin cancer include thiazides, angiotensin-converting-enzyme inhibitors, cotrimoxazole, tetracyclines, and azoles. On the other hand, long-term use of NSAIDs including those that are photosensitisers, seems to reduce the risk of developing cutaneous SCC. Photosensitivity also has a direct relationship with photoaging. Concerns about the adverse effects of using light therapies like lasers are not supported by any published reports. This further supports the view that photosensitivity as described is wavelength specific.
A recent systematic review that included 19 studies found that between 31% and 39% of photosensitive patients suffered a very large impact on their quality of life. Employment, education, social and leisure activities, and clothing choices were most affected. The study also confirmed that the levels of anxiety and depression were twice those of the general population. Involvement of the face, being female, and an earlier age of onset were associated with significantly more severe psychological morbidity. This study confirmed findings from multiple previous studies and highlights the hidden toll of photosensitivity on sufferers. There are limited data on the psychosocial impact of photosensitivity focusing on pigmented skin. The additional impact of more severe dyspigmentation is likely to exacerbate the psychosocial impact of photosensitivity in this population, more so if HIV-infected as both these are independent predictors of poorer quality of life and psychosocial morbidity.