CASE REPORT Ref: Ro J Rheumatol. 2018;27(2) DOI: 10.37897/RJR.2018.2.6 SCLERODERMA – LUPUS OVERLAP SYNDROME: CASE REPORT Gabriela Ticu1, Marius Ioan Balea2, Camelia Badea1,3, Adelina Silvana Gheorghe1,4, Ruxandra Patrascu1,3 1Internal Medicine Department, Colentina Clinical Hospital, Bucharest 2Pneumology Department, Colentina Clinical Hospital, Bucharest 3Carol Davila University of Medicine and Pharmacy, Bucharest 4Prof. Dr. Alexandu Trestioreanu Institute of Oncology, Bucharest Abstract The overlap syndromes are a diverse group of conditions that usually have characteristic features of at least two well-defined rheumatic diseases occurring together. We present the case of a 32-year-old patient who sequen- tially develops manifestations of systemic lupus erythematosus and systemic sclerosis. The first manifestation of the disease was the pleural effusion and, over time, the patient associated various other complications which influenced the diagnostic course. Digital ulcerations associated to scleroderma have evolved into ischemic necro- sis lesions, requiring amputation. This case is a clinically suggestive example of the complexity of autoimmune diseases, of associations between pathologies and unexpected evolutions, requiring constant and long-term follow-up of the patients. Keywords: systemic lupus erythematosus, serositis, systemic sclerosis, digital ulcers, overlap syndrome INTRODUCTION CASE PRESENTATION Clinicians are often challenged by the clinical is- We are presenting the case of a 32 years old sues when confronting with patients who either pres- woman, ex-smoker (10 pack-years, quit smoking 3 ent an undifferentiated rheumatic disease or an over- years ago), with class III obesity (body mass index lap syndrome. In the medical literature, it is 58.2 kg/m2) and a history of abortion on demand one appreciated that approximately 25 percent of pa- month prior to the admission at the hospital. She de- tients with rheumatic diseases cannot be definitely scribes left posterior thoracic pain, night rigors, fe- diagnosed with a single well-characterized systemic ver (38.5ºC), followed by decreased effort tolerance rheumatic disease (1,2). Moreover, some of them re- and dyspnea on minimal exertion, installed two main undiagnosed for a long period of time, despite weeks before presentation. The patient also com- plains of morning joint stiffness, especially in the periodical reassessments and expectant management wrists, which had intensified in the last month. (1,2). It happens due to the fact that this category of From the pathological personal history, it is worth patients exhibits several patterns, manifesting multi- mentioning that the patient followed 6 months of tu- ple nonspecific serologic or clinical abnormalities, berculostatic treatment, 9 years ago, for positive sometimes of more than one defined disorder. Some Mantoux tuberculin skin test, but without suggestive examples include rheumatoid arthritis – lupus (rhu- chest radiography or confirmation of tuberculosis pus), scleroderma – polymyositis/dermatomyositis, through sputum smear microscopy. scleroderma – lupus, scleroderma – rheumatoid ar- Physical examination on admission to the hospi- thritis, Sjögren‘s syndrome overlaps and others (1). tal revealed that the patient was afebrile, tachypneic Correspondence address: Gabriela Ticu, Colentina Clinical Hospital, 19-21 Stefan cel Mare Road, Sector 2, Bucharest, Romania E-mail: [email protected] 84 ROMANIAN JOURNAL OF RHEUMATOLOGY – VOLUME XXVII, NO. 2, 2018 ROMANIAN JOURNAL OF RHEUMATOLOGY – VOLUME XXVII, NO. 2, 2018 85 with a respiratory rate of 24 breaths per minute and diaphragmatic recess. The rest of the investigations tachycardic with a ventricular rate of 104 rhythmic (electrocardiogram, echocardiogram, abdominal and beats per minute (regular heart rhythm). The vesicu- pelvic ultrasound, lower extremity veins Doppler ul- lar murmur was abolished with dullness to percus- trasound) did not show any relevant particularities. sion over left lung base and decreased breath sounds The patient underwent thoracentesis of the left bilaterally. A bilateral hand edema could also be ob- pleural effusion. The fluid obtained had the charac- served. The blood pressure was normal, without pul- teristics of an exudate, with 2.400 cells/mm3, 46% monary crackles, cardiac murmurs or extra sounds neutrophils and 27% lymphocytes, but with negative and no evidence of arthritis or rashes. bacterial cultures. Examination by Ziehl-Neelsen Since the onset of symptoms, prior to the admis- staining did not reveal acid-alcohol-resistant bacilli, sion in the hospital, the patient presented to the gen- the level of adenosine deaminase in the effusion liq- eral practitioner, who recommended chest radiogra- uid was normal and Mycobacterium tuberculosis phy, computed tomography (CT) scan of the thorax DNA was not detected by polymerase chain reac- and pleural ultrasound. At these investigations, a tion. Also, the histopathological examination of the pleural biopsy was normal. small pleural effusion was discovered in the left Despite having received antibiotic (ceftriaxone), lung, along with atelectasis aspect or pulmonary pa- anti-inflammatory and antialgic (celecoxib) treat- renchyma condensation (Fig. 1). No direct or indi- ment, subfebrility persisted, only with a minimal im- rect signs of pulmonary embolism have been detect- provement of the thoracic pain. ed. After 10 days, the patient was admitted again in The episode was interpreted as the an intercurrent the hospital for paroxysmal nocturnal dyspnea, per- respiratory infection, with secondary pleural reac- sistence of the thoracic pain and dyspnea on minimal tion and the patient received broad-spectrum empiric exertion. Clinical examination and several investiga- antibiotic therapy: 6 days of levofloxacin, followed tions (thoracic ultrasound, echocardiography and CT by 3 days of ciprofloxacin and 5 days of drug com- scan) led to the discovery of pericardial and bilateral bination (gentamicin, amoxicillin/clavulanic acid pleural effusions. During thoracic ultrasound, an im- and metronidazole). Under this treatment, she con- portant right diaphragmatic elevation with low mo- tinued to develop fever (38.2-38.5ºC). bility of the diaphragm was also noticed. We identified an important inflammatory pro- The serological tests revealed positive anti-nu- cess, based on the elevation of serum biomarkers: clear antibodies, C3 hypocomplementemia, pres- C-reactive protein (146.55 mg/L), erythrocyte sedi- ence of lupus anticoagulant and high-titer anti-cardi- mentation rate (61 mm/1h) and fibrinogen (915 mg/ olipin IgM antibodies (antiphospholipid antibody dL). The complete blood count showed discrete ane- positivity). Anti-double stranded DNA (dsDNA) an- mia, thrombocytosis, without leukocytosis or leuko- tibodies, anti-Ro antibodies, anti-beta2-glycoprotein penia. Serum creatinine and microscopic urinalysis I IgG antibodies, anti-cardiolipin IgG antibodies were normal. were negative, as well as the rheumatoid factor and We also performed chest radiography after ad- direct Coombs test. mission, which revealed the same aspect of pleural These three immunological criteria, added to the effusion in small amounts, located in the left costo- forth clinical criterion (serositis, consisting in pleuri- FIGURE 1. Chest radiography and computed tomography scan of the thorax showing small pleural effusion in the left lung (with a maximum of 2 centimeters in transversal diameter at the ultrasound examination) 86 ROMANIAN JOURNAL OF RHEUMATOLOGY – VOLUME XXVII, NO. 2, 2018 sy and pericarditis), led to the classification and then The switch in the patient’s dominant signs and diagnosis of systemic lupus erythematosus (SLE) symptoms guided us to discover a second autoim- with minimal articular involvement (based on the mune illness: systemic sclerosis (SSc) or scleroder- aforementioned morning joint stiffness) – according ma. Meeting the classification criteria for two sepa- to SLICC (Systemic Lupus International Collaborat- rate well-characterized rheumatic diseases, SLE and ing Clinics) classification criteria 2012. Due to the SSc, we came to the final diagnosis of overlap syn- presence of progressive dyspnea, accompanied by drome between the two diseases. pleuritic chest pain, diaphragmatic elevation and The patient received treatment with corticoster- lung volume reduction, we suspected a rare compli- oid, anti-malaric, sulodexide and pentoxifylline, as cation associated with lupus, the shrinking lung syn- well as topical dermatological preparations for the drome, but this has not been confirmed. ischemic lesions. She was advised to avoid cold ex- Under treatment with systemic corticosteroids posure and to quit smoking. No further actions were (Dexamethasone, followed by Methyl-prednisolone) taken for the next 5 months, as the patient did not and anti-malarial drug (Hydroxychloroquine), the present to the hospital for immunosuppressive thera- patient had a favorable evolution, both clinically and py and association of anticoagulation. During this biologically. time, she underwent gynecological assessments in Over the following two months, the patient did the private healthcare system. The cervical biopsy not experience fever, dyspnea or thoracic pain, so we showed the presence of an intraepithelial squamous advised her to continue the treatment with corticos- lesion, positive for Human papillomavirus DNA teroid and hydroxychloroquine as well as to lose (high-risk genotype). weight. At the following