Photolichenoid plaques with associated vitiliginous pigmentary changes
Published Web Locationhttps://doi.org/10.5070/D308t049xp
Photolichenoid plaques with associated vitiliginous pigmentary changesDepartment of Dermatology, New York University, New York, New York
Kathleen Tran MD MSc, Rachael Hartman MD, Julia Tzu MD, Shane Meehan MD, Scott E Sanders MD, Miriam Keltz Pomeranz MD, Miguel
Dermatology Online Journal 17 (10): 13
A 49-year-old man with advanced HIV/AIDS on anti-retroviral therapy (HAART) and trimethoprim-sulfamethoxazole (TMP-SMX) presented with a several-month history of pruritic, erythematous, lichenified papules that coalesced into hyperkeratotic plaques on the trunk and extremities in a sun-exposed distribution. He shortly thereafter developed a progressive depigmentation over more than 80 percent of his body surface area. A biopsy specimen of an erythematous plaque on the trunk showed a superficial and mid-dermal infiltrate of lymphocytes with eosinophils, most consistent with either chronic lichenoid drug eruption or atypical lymphoproliferative disorder (ACLD) of HIV. The patient’s lichenoid skin disease has persisted despite discontinuation of TMP-SMX, although it has improved partially with administration of topical glucocorticoids and acitretin. His depigmentation has continued to progress. We discuss the overlapping diagnostic entities which may be comprised by this patient’s clinical disease, and highlight a unique presentation of the complex interaction between HIV infection and the skin.
A 49-year-old man with advanced human immunodeficiency virus (HIV) infection, newly started on highly active anti-retroviral therapy (HAART) and trimethoprim-sulfamethoxazole (TMP-SMX), originally presented to the dermatology clinic of Bellevue Hospital Center in May, 2008, with an intensely pruritic eruption on his trunk, upper and lower extremities, and ears. Shortly after the onset of this eruption, he developed widespread depigmentation of his body, which began on the face, knees, and elbows and eventually progressed to encompass more than 80 percent of the skin surface. Initially, the patient was treated with topical glucocorticoids. A trial of narrow-band ultraviolet B (UVB) phototherapy was initiated, but discontinued after a few sessions because of recurrent burning. In September, 2008, the patient became erythrodermic with desquamation over much of his body surface area. TMP-SMX was discontinued, and prednisone was administered, which resulted in temporary improvement. Despite these measures, the papular eruption persisted. In December, 2008, acitretin 25 mg daily was started in addition to topical glucocorticoids, resulting in partial improvement in the lesions and pruritus, but no effect on the dyspigmentation. The clinical course has been complicated by multiple episodes of bacteremia and ear infections with methicillin-resistant Staphylococcus aureus (MRSA), herpes simplex virus (HSV), and Pseudomonas aeruginosa that required admission. As these infections appear to worsen during times of acitretin administration, his acitretin has been decreased to 25 mg three times per week. The patient did not have phototesting.
Over 80 percent of the body surface area is depigmented, with areas of sparing of the central face and in the popliteal and antecubital fossae. On the face, trunk, arms, and legs, there are erythematous, lichenified papules that coalesce into hyperkeratotic plaques, which are most pronounced on the helices of the ears, upper chest, distal aspects of the forearms and hands, and lower legs down to the ankles, roughly in a sun-exposed distribution. Examination of lymph nodes showed, nontender, bilateral axillary and inguinal lymphadenopathy.
A white-cell count was 3600 x 109/L with 16.8 percent lymphocytes and 15.9 percent eosinophils. CD4 T-cell subset was 39 cells/mm³. Human-immunodeficiency viral load was 386 copies per milliliter. CD4 to CD8 ratio was reversed at 0.27. B cells expressed pan B-cell markers and were polyclonal. Molecular studies were negative for monoclonal T-cell receptor gamma chain gene rearrangements and negative for human T-lymphotrophic virus type I. Liver function tests and basic metabolic panel were normal. A chest radiograph showed stable prominence of the interstitial markings with no acute cardiopulmonary disease.
There is psoriasiform epidermal hyperplasia with mild spongiosis, hypergranulosis, and compact orthokeratosis. There is a perivascular and focally lichenoid, lymphocytic infiltrate with some eosinophils.
HIV infection is known to be associated with a vast array of skin diseases. This patient with advanced HIV/AIDS presented with an eruption of pruritic, erythematous papules that coalesced into hyperkeratotic plaques in a roughly sun-exposed distribution and were succeeded by a widespread, vitiliginous depigmentation that has now encompassed more than 80 percent of his body surface area. The differential diagnosis of his skin disease highlights a number of clinical entities that include atypical cutaneous lymphoproliferative disorder of HIV, chronic actinic dermatitis, HIV photodermatitis, chronic lichenoid drug eruption, pseudolymphoma, HTLV-I infective dermatitis, and cutaneous T-cell lymphoma (CTCL).
Atypical cutaneous lymphoproliferative disorder (ACLD) of HIV is an inflammatory, pruritic, persistent, papular eruption in a widespread distribution. First described in 1989 , ACLD occurs in immunocompromised HIV-infected patients and is frequently associated with pigmentary changes that include both hyperpigmentation and hypopigmentation. Histopathologic features include atypical CD8+ lymphocytes. Atypical cutaneous lymphoproliferative disorder has therefore been referred to as pseudo-Sézary syndrome. Clinically, however, ACLD does not resemble CTCL and the relationship between ACLD and CTCL is not yet clear. In a 1999 retrospective analysis of 16 patients with ACLD conducted at NYU VA Medical Center, only one patient went on to develop CTCL . It therefore appears that despite the atypical cutaneous lymphocytic infiltrate present histopathologically, ACLD seldom progresses to lymphoma. Effective treatments for ACLD also have yet to be developed; the same retrospective study found that treatment with a variety of therapies, which included topical glucocorticoids, NB-UVB, PUVA photochemotherapy, retinoids, and hydroxychloroquine was generally not effective in alleviating symptoms or altering disease course.
Owing to the lymphocytic infiltrate demonstrated in the biopsy specimen, CTCL also may be considered in the differential diagnosis. This patient has been found at times to have a waxing and waning axillary and inguinal lymphadenopathy. However, no definitive immunotypic evidence of lymphoma or leukemia has been identified by flow cytometry and assays for HTLV-1 and polyclonality of B cells also were negative. He has not yet followed up for pelvic lymph node biopsy, although this, along with peripheral blood smear with assay for circulating Sézary cells and serum LDH, also could be useful studies.
Whereas the above hematologic disorders could account partially for this patient’s clinical presentation, the photodistribution of the papular eruption also raises several other important considerations. The first of these is photosensitivity associated with HIV, which may result in depigmentation that resembles vitiligo. Photosensitivity has been found in about 5 percent of HIV-infected persons , and, although generally associated with CD4 counts below 200 cells/mm³, it may be the initial manifestation of HIV infection. Among HIV-infected individuals, African-American men and patients taking photosensitizing medications, which include NSAIDs and trimethoprim-sulfamethoxazole (TMP-SMZ) are disproportionately affected.
This patient was taking both TMP-SMX and HAART around the time of onset of his skin disease. This finding, along with the patient’s skin biopsy findings and high percentage of circulating eosinophils, suggest a photodrug eruption. Although HIV infection usually leads to anergy to immune stimuli, the incidence of drug hypersensitivity reactions is increased in HIV-positive individuals. For instance, HIV-seropositive patients with CD4 counts below 200 cells/mm³ have a 10- to 50-fold increased risk of cutaneous eruption to TMP-SMX, which depends on the administered dose . A recent report documented a case of generalized depigmentation after a sulfonamide-induced drug eruption . Another study documented a series of lichenoid photoeruption cases in HIV-infected individuals; most of these had received either NSAIDs or TMP-SMX. Two of these patients experienced depigmentation at the sites of their lesions, which persisted and extended even after the original eruptions resolved . As such, TMP-SMX could certainly be an offender in this patient. However, his papular eruption has persisted despite discontinuation of TMP-SMX for more than one-and-one-half years (last dose March 2009).
The use of HAART is also an independent risk factor for development of HIV-associated photosensitivity . This patient was taking Atripla (tenofovir, emtricitabine, efavirenz) at the time of onset of his eruption. Since then, his HAART regimen has been modified several times and now consists of tenofovir, emtricitabine, atazanavir, norvir, and ritonavir. A case of lichenoid drug eruption secondary to tenofovir has been published , although owing to medical necessity, tenofovir has been continued in this patient. Several cases of photosensitive dermatitis related to efavirenz also have been reported [8, 9, 10].
Of the HIV-associated photosensitive eruptions, chronic actinic dermatitis (CAD) also is a consideration. Although this patient’s biopsy specimen was more consistent with drug eruption, it is worth noting that CAD may present with scaly, lichenified plaques and marked vitiligo-like depigmentation similar to that observed in this patient. A few cases, which include several from NYU Medical Center, have documented the development of chronic actinic dermatitis as the presenting manifestation of HIV infection [11, 12]. Chronic actinic dermatitis has also been found to be associated with decreased CD4:CD8 ratio in both HIV-negative  and HIV-positive patients .
Although it is unlikely that this patient’s depigmentation developed independently of his papular disease, it should be mentioned that vitiligo also bears a lesser-known association with HIV/AIDS. This association was first described in 1987,  and, wereas it was at first thought by many to be coincidental, an increasing number of case reports in the last decade have linked the appearance and progression of vitiligo with increasing viral load and a decreasing CD4 T-cell count. Repigmentation can occur in these cases after initiating treatment with HAART [16, 17, 18 19]. Although the link between HIV/AIDS and vitiligo is not yet fully understood, some have suggested that HIV results in an immune dysregulation that may result in autoimmunity towards the skin. Others have postulated a direct infection of melanocytes by the HIV virus. HIV is well known to invade the nervous system and melanocytes are derived from neural crest cells .
This patient first presented with eczematous papules and plaques that originally were thought to be HIV-related eczema. However, his condition was not well-controlled with topical and systemic glucocorticoids. Despite discontinuation of TMP-SMX, the patient has continued to develop waxing and waning photolichenoid plaques, which have shown partial improvement with the use of oral acitretin (first trial December 2008). This patient’s course also has been complicated multiple times by bacteremia and severe, recurrent Pseudomonas, HSV, and MRSA infections of both ears. As the latter have appeared to worsen during times of acitretin administration, the capacity to use acitretin and other possibly immunosuppressant therapies has been limited.
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