Systemic lupus erythematosus and Hodgkin disease

We report on the rare association of Hodgkin’s disease with systemic lupus erythematosus. Four years after the diagnosis of systemic lupus erythematosus, the patient developed cervical mass and weight loss. Histological and subsequent clonality studies confirmed classical Hodgkin’s lymphoma. The awareness of the association of Hodgkin’s disease with systemic lupus erythematosus and its modes of presentation will help in the early diagnosis and management of such patients. Besma Ben Dhaou ( ) Corresponding author: besma_2@yahoo.fr Dhaou BB, Boussema F, Aydi Z How to cite this article: et al. Systemic lupus erythematosus and Hodgkin disease [version 1; referees: 1 2012, :31 (doi: ) approved, 1 approved with reservations] F1000Research 1 10.12688/f1000research.1-31.v1 © 2012 Dhaou BB . This is an open access article distributed under the terms of the , which Copyright: et al Creative Commons Attribution Licence permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Data associated with the article are available under the terms of the (CC0 1.0 Public domain dedication). Creative Commons Zero "No rights reserved" data waiver The author(s) declared that no grants were involved in supporting this work. Grant information: Competing interests: No competing interests were disclosed. 18 Oct 2012, :31 (doi: ) First published: 1 10.12688/f1000research.1-31.v1 Referee Status:

v1 Introduction Systemic lupus erythematosus (SLE) is associated with lymphoproliferative diseases such as Hodgkin's lymphoma (HL) 1 .Since there is considerable overlap between the features of SLE and HL there can be a great difficulty in diagnosing HL in the presence of SLE 1 .

Case report
A 35-year-old woman was followed from 2002 for SLE with neuropsychiatric, renal and hematologic involvements.She was treated with only glucocorticoids with favourable outcomes.In April 2006, when she was under steroid treatment of 10 mg/day, she was admitted for cervical mass and weight loss.Physical examination showed a left indolent, fixed and elastic cervical adenopathy.The biological assessment was normal.Computerized tomography of the chest and abdomen showed a left basicervical mass expanded to the anterior and superior mediastinum.Magnetic resonance imaging was suggestive of a thymoma (Figure 1, Figure 2).The cervicotomy showed a supraclavicular mass.Histological and subsequent clonality studies confirmed classical Hodgkin's lymphoma (HL) of the nodular sclerosing type.Viral serology (for Epstein-Barr, herpes simplex, and herpes zoster) was negative.The diagnosis of Hodgkin's disease stage Ia was retained and the patient was transferred to hematological department where she was treated by chemotherapy (adriamycin, bleomycin, vinblastine and dacarbazine) with favourable outcomes.She is being currently followed in our department and is in remission of her lupus and Hodgkin's disease.

Discussion
The relative risk of hematologic malignancy is estimated to be 60% higher in patients with SLE than in the general population, the reason being unknown 1 .Of all hematologic cases reported in patients with SLE, the most common is non-Hodgkin's lymphoma followed by Hodgkin's disease, leukemia, and then multiple myeloma 1 .
The initial presenting features of SLE and Hodgkin's disease are similar, with fever, weight loss, and peripheral lymphadenopathy seen in most cases 1 .Our patient presented with weight loss and cervical adenopathy.
Persistent large lymph nodes not responding to conventional therapy in SLE should be biopsied for alternative diagnosis (i.e., lymphoma) 1 .

Editorial note:
Please note that the refereeing status of this article was changed from "indexed" to "[v1; ref status: approved 1, approved with reservations 1]".
When this article was first published, F1000Research was still in its beta phase; during this period articles that received any two of "Approved" or "Approved with Reservations" statuses from the reviewers were labelled as "indexed".When the journal was formally launched in January 2013, the requirements for indexing were tightened, and only articles that are given either two "Approved" or one "Approved" plus two "Approved with Reservations" statuses by the reviewers are labelled "indexed".
The new criteria for "indexing" can still be met in the future if a new revised version receives the necessary approval status from the reviewers.Several conditions and links have been identified that could potentially predispose patients with SLE to cancer (Table 1) 2,3 .
A side-effect of immunosuppression is a possibility, as is intercurrent viral infection due to, for example, Epstein-Barr, herpes simplex, herpes zoster and polyoma viruses, which are potentially oncogenic.In our case, viral serology was negative.Patients who have had a renal transplant are known to have an increased risk of cancer 4 .They are, however, treated with much higher doses of immunosuppressive agents than patients with lupus.
In the studies of Petterson et al. 5 , Abu-Shakra 6 and Sultan et al. 7 , the use of cytotoxic agents was not related to the occurrence of malignancy.Our patient was treated only with corticosteroids.It may be that the disease itself confers an increased risk.Patients with SLE have defects in both their cellular and humoral immune systems.
The mechanisms of hematologic malignancies 8 are thought to be related to the following: • Failure or dysregulation of apoptosis as a result of mutated genes in SLE (Fas ligand).
• Accumulation of and mutations in B and T lymphocytes in the lymph nodes.
• Exposure to immunosuppressive medications (possible increased risk of EBV infection in patients with SLE) 9 .
Large multicenter studies are required to adequately address the risk of developing malignancies in large cohorts of patients with SLE and to address issues such as associated risk factors and additional confounding factors, such as deprivation and exposure to therapy.The chance of detection of malignancy may vary due to factors such as access to health services, which vary widely and are not uniformly available, and may therefore underestimate the risk of malignancy.

Conclusion
SLE has been associated with increased frequency of neoplasia, lymphoma, leukaemia and epithelial tumours.Hodgkin's disease has been occasionally associated with SLE in adults.An awareness of the association of Hodgkin's disease with SLE and the modes of presentation will help in the early diagnosis and clinical management of such patients.

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Similarities between SLE immunologic disturbances and B-cell malignancies ○ Abnormalities in survival, proliferation, and differentiation of lymphocytes ○ Similar defects in apoptosis ○ Chronic antigenic stimulation (can lead to lupus-like autoimmunity and B-cell lymphomas in mice models of graft-versus-host disease) Growth and hormonal factors* ○ Insulin-like growth factor ○ Prolactin ○ Growth hormone ▪ Viral triggers ○ Epstein-Barr virus ▪ Other ○ Secondary Sjögren syndrome ○ Exposure to cytotoxic and immunomodulatory drugs used to manage SLE ○ Increased prevalence of traditional risk factors for malignancies (e.g., nulliparity, obesity) in patients with SLE

Table 1 . Potential links between systemic lupus erythematosus and malignancy.
3rowth and hormonal factors may play a role in autoimmunity as well as in malignancy3. *