Alopecia areata and vitiligo as primary presentations in a young male with human immunodeficiency virus.

A 26-year-old Chinese male consulted with the team regarding his alopecia areata and vitiligo for which previous treatment was ineffective. The patient, a homosexual man, denied having a history of drug abuse and of blood transfusion. No member of his family had vitiligo or alopecia. Laboratory studies revealed that the serum for anti-human immunodeficiency virus (HIV) antibody was positive. The patient's CD4 lymphocyte count and CD4/CD8 ratio were both strikingly low (20 cells/mL and 0.04), but no other complaints or opportunistic infections were reported. One month after antiretroviral therapy, the patient's alopecia areata dramatically improved, but no evident improvement in his vitiligo was found. This case is a very rare case of alopecia areata and vitiligo associated with HIV infection that might be attributed to the generation and maintenance of self-reactive CD8+ T-cells due to chronic immune activation with progressive immune exhaustion in HIV infection.

What was known?

Cutaneous complications caused by human immunodeficiency virus are frequently reported.

Introduction

Cutaneous complications caused by human immunodeficiency virus (HIV)/acquired immune deficiency syndrome have been reported, including, all kinds of opportunistic infections, psoriasis, seborrheic dermatitis, hairy leucoplakia, and granuloma annulare, among others.[12] Alopecia areata and vitiligo are generally frequent in patients, and their solitary associations with HIV are probably fortuitous in most cases.[3] In the current paper, we report a case of an HIV-infected patient with these conditions.

Case Report

A 26-year-old Chinese male presented with hair loss and depigmented macules. Two years ago, several dispersed hair-loss patches appeared on the patient's scalp without any subjective symptom. Six months ago, several depigmented macules appeared on his face and neck. He previously visited a dermatologist and was diagnosed with alopecia areata as well as vitiligo. However, the treatment was ineffective. The patient, a homosexual man, denied drug abuse and blood transfusion. No member of his family had vitiligo or alopecia.

Dermatological examination revealed several depigmented macules measuring 2 cm to 5 cm with clear boundaries distributed on the face and neck. Several smooth hair-loss patches measuring 1-2 cm were also distributed on the top of the head, and diffuse alopecia was observed around the head [Figure 1a, b, and c].

Figure 1

Alopecia areata and vitiligo before antiretroviral therapy. (a) Hair loss at his first visit to the clinic; (b) and (c) Status of vitiligo at his first visit; (d) Hair loss at his second visit a month later

Enzyme-linked immunosorbent assay and Western blot revealed a positive result for serum anti-HIV antibody. Flow cytometry revealed that the patient's CD4 lymphocyte count and CD4/CD8 ratio were 20 cells/μL (3.7%) and 0.04, respectively, which are considerably low. The thyrotropic-stimulating hormone and free thyroxine levels were 7.69 μIU/mL and 10.06 pmol/L, respectively. Serological test of syphilis showed a positive T. pallidum particle agglutination, but the toluidine red unheated serum test was negative.

The patient did not accept any therapy for 1 month until his second visit to the clinic. His alopecia areata worsened, presented ophiasis pattern with 80% hair loss on his head, and even his brows [Figure 1d]. The patient's general state of health was still good, and manifestations of opportunistic infection and malignant tumor were not observed.

One month after antiretroviral therapy (ART), the patient's alopecia areata dramatically improved, but no evident improvement in his vitiligo was found [Figure 2]. Laboratory results revealed that his CD4 lymphocyte count increased to 40 cells/μL. His CD8 lymphocyte count had a more considerable increase, resulting in a CD4/CD8 ratio of 0.03. Although, his CD4 lymphocyte count was still very low, no other complaints were reported. The patient received benzathine penicillin injection for 3 times, but his vitiligo was not still improved.

Figure 2

Alopecia areata and vitiligo after antiretroviral therapy (a) and (b) Status of alopecia areata dramatically improved; (c) and (d) Vitiligo did not have obvious improvements

Discussion

Alopecia areata is one of the most common autoimmune diseases that can be considered a T-cell-mediated autoimmune disease, whereby the gradual loss of protection provided by the immunity of normal hair follicle plays an important role.[4] Alopecia areata has been shown as a CD8+ T-cell-dependent and organ-specific autoimmune disease in a rat model of alopecia areata,[5] in which depleting CD8+ T-cells could restore hair growth.

Vitiligo is a common depigmentation disease characterized by the presence of circumscribed white macules in the skin caused by the destruction of melanocytes in the epidermis. Studies have shown the participation of autoimmune processes in the pathogenesis of vitiligo.[6] Skin biopsies of vitiligo patients show that inflammatory cells are prominent in the perilesional areas, consisting of CD8+ and CD4+ T-cells, often with an increased CD8+/CD4+ ratio.[7]

Although, syphilis infection may also cause alopecia areata or vitiligo like lessions, the laboratory studies in this case only confirmed that the patient had been infected with syphilis. The generation of alopecia areata or vitiligo from HIV infection needs to be elucidated. Rawson et al.[8] suggested an autoimmune mechanism that involves the release of protein fragments from dying CD4+ T-cells that, in turn, promote the formation of auto-reactive CD8+ T-cells in HIV infection.[9] The massive level of death and destruction of lymphocytes in HIV infection breaks the tolerance for self-peptides and leads to the production of auto-reactive cytotoxic T-cells that respond to the cleavage products of apoptotic cells.[10] This mechanism explains the successive occurrence of alopecia areata and vitiligo in the same patient with HIV.

Although, the patient's CD4 lymphocyte count was only 20 cells/μL, he had no other complaints, except for alopecia areata and vitiligo. After ART, his CD4 lymphocyte count increased, simultaneously accompanied by improvement in his alopecia areata without anti-alopecia treatment. Hence, the improvement of alopecia areata and increased CD4 lymphocyte count are positively correlated.

The patient represents a very rare case of alopecia areata and vitiligo associated with HIV infection. Self-reactive CD8+ T-cells are generated because the release of protein fragments from dying CD4+ T-cells breaks the tolerance for hidden antigens during progressive immune exhaustion. This mechanism explains the occurrence of some autoimmune diseases, including, alopecia areata and vitiligo, with HIV infection.

Consent

Written informed consent was obtained from the patient for the publication of this case report and any accompanying images.

What is new?

Alopecia areata and vitiligo associated with HIV infection might be connected with the generation and maintenance of self-reactive CD8+ T-cells.