systemic lupus erythematous versus hematologic malignancy ... · polyserositis (pleural effusion...

Systemic Lupus Erythematous versus Hematologic Malignancy in a Patient Presenting

with Elevated ANA and anti-dsDNA, Splenomegaly, and Unilateral Pleural Effusion

By: Erika Lee

Home for the Summer Program - June to July 2019

Dauphin/Ste Rose du Lac, Manitoba

Supervisor: Dr. Laura Sexton, Dr. Catherine Gudmundson

Systemic Lupus Erythematous versus Hematologic Malignancy in a Patient Presenting with Elevated ANA and anti-dsDNA, Splenomegaly, and Unilateral Pleural Effusion

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Abstract Unilateral pleural effusions are commonly caused by infections and malignancy.1 However, in the presence of splenomegaly and elevated antinuclear antibodies (ANA) and double stranded DNA antibodies (anti-dsDNA), the clinical picture is not as clear. Here we report on a patient presenting with shortness of breath and a myriad of atypical symptoms possibly representing Systemic Lupus Erythematous or a hematological malignancy. Case History Description of patientand history of presenting condition

Patient A is a 71-year-old female who presented to the Ste Rose emergency with complaints of worsening shortness of breath and fatigue. This episode started two days prior and has been worse especially on exertion. She also reported an 18kg weight loss with associated weakness since January 2019.

She had a previous episode of a small pleural effusion in February of 2019 that was medically managed in the Ste Rose emergency department. Afterwards, she was referred to Internal Medicine in Dauphin for workup of the pleural effusion. She is postmenopausal. She has a past medical history of endometrial cancer treated in 2017 and her last Tamoxifen treatment was last winter. She also has hypothyroidism that has been managed with Levothyroxine. Physical exam

Patient A appeared pale, weak, with increased work of breathing and an oxygen saturation of 89%, and afebrile. She was also noted to be slower at answering questions and paused often to collect her thoughts. She had asymmetric breath expansion, dullness to percussion, decreased breath sounds, and decreased tactile fremitus on the left side. She had a large spleen on abdominal exam palpated to the mid-clavicular line at the just below the subcostal margin. Relevant lab/X ray/other tests

Her labs in emergency showed pancytopenia with a hemoglobin in the low 80s. She had a slightly elevated creatinine of 120s, which was 30mmol/L from her baseline. Blood cultures were negative.

The preliminary chest x-ray in the emergency department showed a large left sided pleural effusion that was more larger compared to a previous chest x-ray. Thoracentesis was indicated for symptomatic relief and pleural fluid analysis. Approximately 500cc of bloody, slightly cloudy fluid was drained on admission and 350cc was drained the following day. Pleural fluid analysis showed an exudate and was negative for acid-fast bacilli.

Previous to her admission to Ste Rose Hopsital, she was undergoing rheumatological investigations since February 2019 by internal medicine in Dauphin and was found to have elevated ANA and anti-dsDNA. Her CA-125 was normal. An


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abdominal CT from April 2019 showed splenomegaly and ascites, which was repeated in June 2019 and showed the ascites had resolved spontaneously. Initial diagnosis and treatment

On admission, her hemoglobin was in the low 80s and had dropped to the 60s within a 24 hours period. She was very symptomatic, increasingly short of breath even while sitting. She was given 2L oxygen by nasal prongs to manage her low oxygen saturations, which improved during her stay in hospital. Her fatigue, latency of speech, breathlessness, and anemia improved after 2 units of blood. She was also sent to Dauphin for a colonoscopy to investigate the anemia. The colonoscopy results were inconclusive for a gastrointestinal explanation for the low hemoglobin and she was returned to Ste Rose to be monitored. Outcome

As she has anemia with concurrent pleural effusion and elevated autoimmune markers, she is currently undergoing investigation by Hematology and Rheumatology in Winnipeg. Considering her weight loss, fatigue, splenomegaly, pleural effusion, and anemia, both services are deliberating between SLE and hematological malignancy such as lymphoma as a possible diagnosis. Since seeing the patient, her creatinine kinase (CK) was elevated, which is a finding that could be congruent with myositis and related to a Lupus process. She is currently awaiting a bone marrow biopsy to investigate her pancytopenia. Discussion A brief literature review was conducted to answer the clinical question: Among older adult patients presenting with elevated autoimmune markers, splenomegaly, and unilateral pleural effusions, how likely is systemic lupus erythematous versus hematologic malignancy? The search terms used were “unilateral pleural effusion”, “ANA”, “anti-dsDNA”, “lupus”, “SLE”, “leukemia”, “lymphoma”, “pancytopenia”, “splenomegaly”, and “anemia”.

The case in this study presented a difficult problem in diagnosing, especially in a rural setting, as the patient had a constellation of symptoms that were vague and required input and investigations from many subspecialties. This patient’s initial complaint was of shortness of breath caused by a pleural effusion. Pleural effusions are caused by a multitude of pathological processes. In descending order of common etiologies: congestive heart failure, bacterial, malignant, inflammatory, and pulmonary embolism. 2 Medications can also be the culprit behind pleural effusions, however this patient was not on any medications implicated in pleural effusions such as methotrexate, amiodarone, beta-blockers, and nitrofurantoin. Whether the effusion was bilateral or unilateral can also guide clinical suspicion towards different etiologies, for instance heart failure can cause bilateral pulmonary effusions due to high capillary and interstitial hydrostatic pressures while unilateral effusions suggest a localized source of inflammation such as pneumonia or disseminated


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malignancy. 2 Workup for pleural effusions includes a careful drug history to rule out offending agents as well as a chest x-ray. 1 The Tamoxifen she was taking for her now resolved ovarian cancer could potentially have caused the pleural effusion, however is not among the most common drugs that are implicated.3 Especially in a postmenopausal female, investigations must include CA-125 and an abdominal CT to rule out ovarian cancer or benign pelvic tumors causing pleural effusions and ascites as is found in Meigs syndrome. 4 This patient was also known to have pancytopenia, splenomegaly, weight loss, and fatigue, all which are concerning for a hematolymphoid malignancy. The incidence of pleural effusions in acute and chronic leukemias is more rare than the incidence in Hodgkin’s and Non-Hodgkin’s Lymphomas (NHL), which occur at frequency of 20-30%.5 In addition, NHL is more likely to act unpredictably and disseminate to places such as the spleen causing splenomegaly.6 Investigations warranted for pleural effusions from a suspected hematological malignancy are blood work, chest x-ray, diagnostic thoracentesis and cytology, and possibly a bone marrow biopsy. Thoracoscopy can also be an option for definitive diagnosis with a biopsy however is an invasive investigation.5 In cases of massive splenomegaly (>1000g) from lymphoma, splenectomy may be indicated to relieve the mass effect and provide a definitive histological diagnosis. 6 The other possibility on the differential diagnosis was Systemic Lupus Erythematous (SLE) due to her high ANA and anti-dsDNA labs. SLE is a difficult disease to diagnose and can often take clinicians months to years to secure the diagnosis. Lupus is a multi-organ disease that primarily affects the skin, musculoskeletal, hematologic system, renal, and neurologic systems.7 The most common symptoms and diseases reported are fatigue (80-100%), weight loss, arthritis/arthralgias (90%), skin rash, vascular diseases such as Raynaud (50%) and vasculitis (11-36%), nephritis (50%), infection of the gastrointestinal tract (40%), pericarditis (25%), and pulmonary complications including pleural effusions.8 Investigations relevant for the investigation of SLE include a complete blood count, creatinine, urinalysis and urine-creatinine ratio to assess nephropathy, autoimmune workup (erythrocyte sedimentation rate, C-reactive protein, ANA, anti-dsDNA, antiphospholipid antibodies, anti-Sm nuclear antibodies, and complements).9 After alternative diagnoses are excluded, patients who fulfill 4 out of the 11 1997 American College of Rheumatology (ACR) criteria or 4 out of 17 of the 2012 Systemic Lupus International Collaborating Clinics (SLICC) criteria and given the diagnosis of SLE.


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Figure 1. 1997 ACR and 2012 SLICC SLE diagnostic criteria (adapted from UpToDate)9


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Figure 2. Continuation of ACR and SLICC SLE diagnostic criteria (adapted from UpToDate)9


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The most likely diagnosis for this patient contributing to her fatigue, weight loss, polyserositis (pleural effusion and ascites), and splenomegaly is probable SLE, defined by having 2-3 criteria along with another suspicious feature such as elevated acute phase reactants and pulmonary disease.9 The patient also already has hypothyroidism, an autoimmune disease that commonly associates with other autoimmune conditions such as SLE. According to Figures 1 and 2, she only fulfills 3 out of both the 7 (ACR guidelines) and 11 (SLICC guidelines):

1. Abnormal titer of ANA and anti-dsDNA 2. Hematologic disorder with her pancytopenia, and 3. Serositis manifesting as a pleural effusion and ascites.

It is possible that her SLE has not expressed disease in obvious ways, such as rashes and oral ulcers that have not been noticed by the patient or provider. It is important to perform a thorough history focusing on constitutional symptoms, photosensitive rash, and joint pain, and a physical exam of the skin for classic rashes such as malar rash and scalp for alopecia and rashes.8 It is also possible that the pleural effusion is hematologic in origin with a secondary underlying autoimmune condition, however less likely than a singular process. Due to her splenomegaly, weight loss, and fatigue it is still possible that she has lymphoma so it is imperative to follow up with a biopsy of suspicious lymph nodes and a bone marrow biopsy if suspecting bone marrow infiltration of the lymphoma.10 Negative pleural effusion cytology does not rule out lymphoma as the malignant cells may be scarce. 5 Deciding whether to initiate treatment for SLE is incumbent on the clinical situation. In this case, if the patient is stable and well enough in hospital, an appropriate course of action for the clinician is to await results of the bone marrow biopsy before confirming SLE and starting steroids. If the patient is unwell, it is up to the clinician and specialists to advocate for expediting the biopsy and perhaps starting treatment earlier. Conclusion

Patients presenting with a complicated symptomatology can be very difficult to diagnose and subsequently treat, especially in a rural setting. Special lab tests and diagnostics are often take a long time to organize and only if the situation deteriorates will patients be transferred to tertiary centres where subspecialties are more accessible. Therefore, it is only through collaboration between urban specialists and rural staff that patients can receive the treatment that is deserved in a timely fashion.


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adults: British Thoracic Society pleural disease guideline 2010. Thorax. 2010;65(SUPPL. 2). doi:10.1136/thx.2010.136978

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3. Olivier KR, Peikert T. Radiation-induced lung injury. In: UpToDate. 4. Benjapibal M, Sangkarat S, Laiwejpithaya S, Viriyapak B, Chaopotong P, Jaishuen

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6. Djokic M, Plesnik B, Petric M, Trotovsek B. Massive splenomegaly due to B-cell lymphoma: A case report. Int J Surg Case Rep. 2018;48:76-78. doi:10.1016/j.ijscr.2018.05.013

7. Obreja EI, Salazar C, Torres DG. Polyserositis and Acute Acalculous Cholecystitis: An Uncommon Manifestation of Undiagnosed Systemic Lupus Erythematosus. Cureus. 2019;11(6). doi:10.7759/cureus.4899

8. Gladman DD. Overview of the clinical manifestations of systemic lupus erythematosus in adults. In: UpToDate. ; 2018.

9. Wallace DJ. Diagnosis and differential diagnosis of systemic lupus erythematosus in adults. In: UpToDate. ; 2017.

10. Freedman AS, Friedberg JW, Aster JC. Clinical presentation and diagnosis of non-Hodgkin lymphoma. In: UpToDate.

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