Dermatology Online Journal

Diffuse large B-cell lymphoma with lung involvement in a psoriatic arthritis patient treated with methotrexate
Samer Homsi MD, Doru T Alexandrescu MD, Natasa Milojkovic MD, Wissam Abouzgheib MD, Khaled Bachour MD, Yamen Homsi MD, Constantin A Dasanu MD PhD
Dermatology Online Journal 16 (5): 1

Pulmonary and Critical Care Medicine, St. Edwards Mercy Medical Center, Fort Smith, Arkansas. homssx@gmail.com

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Abstract

Non-Hodgkin lymphoma (NHL) occurs in the setting of methotrexate (MTX) therapy for rheumatoid arthritis. However, it has been very rarely reported in subjects with psoriatic arthritis treated with MTX. We report here a case of a 70-year-old woman with psoriatic arthritis who presented with bilateral lung infiltrates, pleural effusion, splenomegaly, and inguinal lymphadenopathy during treatment with MTX. The diagnosis of diffuse large B-cell lymphoma was made by analysis of the pleural fluid via thoracentesis and biopsy of an enlarged inguinal lymph node. Clinicians should consider the possibility of a NHL complicating psoriasis and with MTX therapy in order to prevent treatment delays.

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Introduction

The risk for lymphoma in psoriasis patients may be increased compared to the general population. Two types of lymphomas were shown to predominate in this setting: Hodgkin lymphoma and cutaneous T-cell lymphoma. Non-Hodgkin lymphoma (NHL) also occurs in the setting of rheumatoid arthritis patients treated with methotrexate (MTX).

However, few lymphoma cases have been described to date in patients with psoriatic arthritis in the English literature. We report here a patient with psoriatic arthritis under treatment with low-dose MTX who developed a diffuse large B-cell lymphoma (DLBCL) with lung involvement.

Case report

Figure 1
Figure 1. Plaque-like psoriatic lesions seen in the vicinity of the right knee joint affected by psoriatic arthritis

A 70-year-old woman with a history of psoriasis presented with a chief complaint of dyspnea on exertion, dry cough, and a 23-pound weight loss over six months. She had been treated with MTX 7.5 mg orally weekly for her disabling psoriatic arthritis for the last 8 years. She reported no fever or night sweats. Past medical history was significant for hypothyroidism, hypertension, and gastroesophageal reflux disease. She had been a smoker of half a pack of cigarettes per day for 40 years. Physical exam was remarkable for decreased breath sounds on the left side, accompanied by dullness to percussion in that area. A complete skin examination showed several psoriatic plaques surrounding the knee and the elbow joints bilaterally (Figure 1). Lymph nodes were enlarged bilaterally in the inguinal areas and measured 2.5 to 3 cm in the longest diameter.

Figure 2	Figure 3
Figure 2. Computed tomography (CT) scan of the chest showing bilateral patchy ground-glass opacities, a few nodular infiltrates in the lungs, and a moderate left pleural effusion Figure 3. CT scan of the abdomen showing splenomegaly

Figure 4
Figure 4. CT scan of the pelvis showing bilaterally enlarged inguinal lymph nodes

A chest X-ray showed bilateral diffuse lung infiltrates and a left pleural effusion. A computed tomography (CT) of the chest, abdomen, and pelvis showed bilateral patchy ground-glass opacities and a few nodular infiltrates in the lungs, a moderate left pleural effusion, and splenomegaly (Figures 2 and 3). It also confirmed the bilaterally enlarged inguinal lymph nodes (Figure 4). A complete blood count, metabolic panel, liver function tests, and lactate dehydrogenase were normal. Thoracentesis demonstrated an exudative effusion with lymphocytic predominance, later proven to represent a kappa-restricted monoclonal population of B-cells. Flow cytometric examination showed the lymphocytes to bear a CD19+CD20+CD43+ immunophenotype. Bronchoalveolar lavage (BAL) stain and culture were negative for bacterial, mycobacterial, viral, or fungal infections, including Pneumocystis jirovecii (P. jirovecii). Bronchoalveolar lavage showed lymphocytic predominance with a decrease in the CD4+/CD8+ lymphocyte ratio, in contrast to what is observed in MTX lung toxicity, in which the CD4+/CD8+ lymphocyte ratio is increased. A transbronchial biopsy was inconclusive. Subsequently, an inguinal lymph node biopsy demonstrated involvement with diffuse large B-cell lymphoma (DLBCL) (Figure 5). A bone marrow aspiration and biopsy, performed for staging purposes, was negative for any evidence of lymphoma.

Figure 5	Figure 6
Figure 5. Diffuse large B-cell lymphoma (DLBCL) involving the inguinal lymph node and featuring large-sized lymphoid cells with oval to round nuclei, vesicular chromatin, multiple nucleoli, and moderately abundant cytoplasm. (H&E stain, original magnification 400X) Figure 6. Chest CT showing a complete resolution of the pulmonary infiltrates and pleural effusion after R-CHOP chemotherapy

Methotrexate was withheld and the patient was treated with chemotherapy, which included rituximab, cyclophosphamide, adriamycin, vincristin, and prednisone (R-CHOP) for a total of six cycles that led to a complete resolution of the pulmonary infiltrates, pleural effusions, and lymphadenopathy (Figure 6).

Discussion

Psoriasis represents a relatively common systemic inflammatory disease. Few studies have suggested an increased frequency of lymphoma in psoriasis patients compared to the general population [1, 2]. However, the absolute risk attributable to psoriasis is considered low given the fact that lymphoma in this setting is rare. In a retrospective cohort from England looking at patients 65 years or older, patients with psoriasis had a 2.95 relative rate of developing lymphoma (95% confidence interval, 1.83-4.76) in comparison with those without psoriasis [1]. In another large retrospective study looking at the frequency of each type of lymphoma in patients with psoriasis, malignancy risk was highest for Hodgkin lymphoma and cutaneous T-cell lymphoma [2].

Although B-NHL is well-described in the setting of MTX use in rheumatoid arthritis patients [3, 4], it has been rarely reported in the setting of psoriatic arthritis [5, 6, 7]. The first report to show this association was by Paul et al., who reported the occurrence of a B-cell lymphoproliferative disorder in a patient with psoriasis being treated with low-dose MTX [6]. Subsequently, Hsiao et al. described a patient with an aggressive diffuse large B-cell lymphoma with immunoblastic features and plasmacytic differentiation in a patient with a severe form of psoriasis under treatment with high-dose MTX [7]. Furthermore, some B-lymphomas occurring in this setting were shown to be associated with the presence of Epstein-Barr virus (EBV) genome inclusions in the neoplastic tissue [6, 7, 8]. EBV-related B-cell lymphomas were reported to regress spontaneously after MTX discontinuation, which is similar to the situation created in immunosuppressed patients after various forms of solid organ transplants [9].

It has been hypothesized that because psoriasis is a disease of immune activation, showing an increased T-lymphocyte activity via antigen stimulation, it may by itself be a risk factor for lymphoma. Nevertheless, it is not entirely clear whether the increased risk of lymphoma in psoriasis patients is related to the pathophysiology of psoriasis itself, immunosuppressive therapy with MTX and other immunosuppressants, or both. Moreover, these influences may be subtle, as pointed in a UK retrospective study looking at psoriasis patients 65 years or older, in which the incidence of lymphoma changed little when the patients treated with MTX were excluded [1].

We conclude that NHL can affect psoriatic arthritis patients treated with MTX. Few reports indicate that it may occur with an increased frequency in this group of patients when compared with data in the general population. Therefore, clinicians should keep in mind the possibility of NHL in psoriatic patients treated with MTX in order to ensure early recognition.

References

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