Lymphomatoid papulosis presenting as a rash in a patient with HIV infection

Background

Rashes are a common presentation in people living with human immunodeficiency virus (HIV), which can be due to a multitude of aetiologies ranging from seroconversion to medication. We present a rare case that was investigated by Dermatology with the need for life-long follow-up.

Case report

A 43-year-old Malaysian man was diagnosed HIV positive in October 2013 on routine screening. Baseline bloods showed a CD4 cell count of 330 cells/µL (26%) and plasma HIV RNA of 46,000 copies/mL. After initial diagnosis, he started on combination antiretroviral therapy with Eviplera® in January 2014. He became virologically suppressed and maintained that until his transfer to our centre in May 2016. Upon his transfer, the patient had no medical history except for previous perianal warts and was on no medication except his antiretrovirals.

The patient attended clinic in September 2016 complaining of a six-week history of widespread rash. The rash started on his chest and had gradually spread to rest of the body including face, back and limbs. New lesions were developing on a daily basis. The rash was not symptomatic and he was otherwise fit and well and had no systemic involvement. There was no palpable lymphadenopathy or hepatosplenomegaly.

On examination, there were multiple erythematous/violaceous nodules distributed over the whole body and face with no oromucosal involvement (Figures 1 and 2). The lesions varied in size from 0.5 cm to 1.5 cm. Bloods were taken and showed a CD4 cell count of 570 cells/µL (52%) and an undetectable HIV viral load. Syphilis serology was negative, C-reactive protein <1 and full blood count, kidney, liver and thyroid profiles were all within normal ranges, indicating no systemic involvement. The patient was seen urgently by Dermatology who performed two 5-mm skin biopsies from lesions on his right thigh. Bacterial cultures, mycobacterial cultures, Ziehl-Neelsen, DPAS and Grocott stains were negative. In the dermis, a small number of atypical cells with enlarged nuclei, nucleoli and increased cytoplasm were noted. (Figure 3) These cells were clustered in loose groups within surrounding inflammatory cells. Immunostaining showed CD30 positivity and negative for ALK-1, EMA and CD15 (Figure 4). There was widespread background positivity for T-cell lymphocyte markers. Histological, morphological and immunophenotypic features together with clinical correlation are in keeping with a diagnosis of lymphomatoid papulosis (LyP) type A.

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Figure 1.

Multiple erythematous/violaceous nodules on the patient’s thigh.

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Figure 2.

Multiple erythematous/violaceous nodules on the patient’s thighs.

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Figure 3.

Haematoxylin and eosin-stained section of the dermis (light microscopy 400× magnification). There is a mix of neutrophils, eosinophils and histiocytes.

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Figure 4.

CD30 immunohistochemistry (400× magnification) showing the large anaplastic cells that stained brown amongst the inflammatory cells.

The patient was reviewed in Dermatology two weeks after his original presentation; by this time the majority of lesions had resolved without need for treatment, leaving behind areas of post-inflammatory hyperpigmentation.

Discussion

LyP is a rare skin disorder that is characterised by crops of self-healing skin lesions that may be erythematous papules or nodules that can ulcerate. ¹ LyP was first characterized by Macaulay in 1968 as a rare dermatosis that is clinically benign but histologically malignant. ² A minority of cases (up to 10%) can progress to malignant lymphoma. It is therefore considered a low-grade lymphoproliferative disease. ¹ The estimated incidence is 1.2–1.9 cases per million, ³ with a 10-year survival rate close to 100%. ⁴ Typically, the lesions occur in crops of 10–20 papules affecting any body part, measuring less than 2 cm, ⁴ with each lesion lasting 2–8 weeks. ⁵ The atypical lymphocytes present in LyP are activated T cells of two types, and this distinction is responsible for the histologic subdivision into Type A and Type B. ⁶ Type A resembles Hodgkin’s disease with up to 20% of large CD30⁺ lymphocytes. Type B resembles mycosis fungoides showing an infiltrate of CD4⁺ lymphocytes and scattered CD30⁺ cells. ¹ The lesions of LyP can histologically resemble several other entities and therefore clinicopathologic correlation is crucial in obtaining the correct diagnosis.^1,7 In most patients, the condition tends to be chronic, with this chronicity and benign clinical course setting LyP apart from cutaneous anaplastic T-cell lymphoma and Hodgkin’s disease, which are major entities in the histological differential diagnosis. ¹ Other clinical differential diagnoses include arthropod bites, scabies, folliculitis, pityriasis lichenoides chronica, pityriasis lichenoides et varioliformis acuta, as well as papular mycosis fungoides. As this condition usually undergoes spontaneous remission, treatment is rarely needed. However, treatment can be given and is guided by symptoms such as pruritus or to achieve cosmesis on the face. Treatment can range from short courses of topical steroids, phototherapy (UVB or PUVA), oral tetracycline antibiotics or methotrexate as well as the anti-CD30 antibody drug conjugate brentuximab vedotin.^1,3,4,5,8

A small subset (up to 10%) of patients with LyP can develop a secondary lymphoma; most commonly mycosis fungoides (T-cell lymphoma) but systemic or cutaneous large-cell lymphoma and Hodgkin’s lymphoma can occur. Therefore, regular clinical follow-up with prompt evaluation of any new clinical symptoms should be emphasised to patients and thoroughly investigated by the clinician.

Although B-cell lymphomas are more prevalent in HIV-positive patients, cutaneous lymphomas in HIV-positive patients are most commonly of T-cell origin. A direct role for HIV in T-cell lymphomagenesis has been suggested. ¹

It has been reported that LyP can sometimes be confused with reactive CD30⁺ lymphoid proliferations, whereby infiltrates of activated lymphocytes occur resulting in CD30⁺ cell populations. In such cases, it is essential that clinical and histological correlation occurs to ensure the correct diagnosis is made. ¹

One other case report has been reported in an HIV patient where the patient was severely immunosuppressed. Clinico-pathological evaluation gave rise to a diagnosis of LyP type B as the infiltrates were mainly CD3⁺ and the scattered larger cells were CD30⁺. The smaller lymphocytes were CD8⁺ rather than CD4⁺ as expected for non-HIV-appointed LyP. The authors speculated that this may be due to immune dysregulation of HIV disease and the absolute and relative paucity of CD4⁺ T cells relative to CD8⁺ T cells.

In summary, HIV patients commonly present with skin rashes and are sometimes referred to Dermatology. This case highlights the importance of swift referral, especially in cases of spontaneous regression, in order to gain the correct diagnosis and to consider a diagnosis of LyP in such patients as well as its malignant counterpart. Finally, long-term follow-up is pertinent in such cases to ensure early detection of malignant transformation.