Email updates

Keep up to date with the latest news and content from Journal of Medical Case Reports and BioMed Central.

Open Access Highly Accessed Case report

Systemic lupus erythematosus associated with sickle-cell disease: a case report and literature review

Mouna Maamar*, Zoubida Tazi-Mezalek, Hicham Harmouche, Wafaa Mounfaloti, Mohammed Adnaoui and Mohammed Aouni

Author Affiliations

Department of Internal Medicine, Ibn Sina Hospital, Rabat, Morocco

For all author emails, please log on.

Journal of Medical Case Reports 2012, 6:366  doi:10.1186/1752-1947-6-366


The electronic version of this article is the complete one and can be found online at: http://www.jmedicalcasereports.com/content/6/1/366


Received:3 August 2012
Accepted:28 September 2012
Published:26 October 2012

© 2012 Maamar et al.; licensee BioMed Central Ltd.

This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Introduction

The occurrence of systemic lupus erythematosus has been only rarely reported in patients with sickle-cell disease.

Case presentation

We describe the case of a 23-year-old North-African woman with sickle-cell disease and systemic lupus erythematosus, and discuss the pointers to the diagnosis of this combination of conditions and also present a review of literature. The diagnosis of systemic lupus erythematosus was delayed because our patient’s symptoms were initially attributed to sickle-cell disease.

Conclusions

Physicians should be alerted to the possible association of sickle-cell disease and systemic lupus erythematosus so as not to delay correct diagnosis and initiation of appropriate treatment.

Keywords:
Sickle-cell disease; systemic lupus erythematosus

Introduction

Sickle-cell disease (SCD) is a prevalent genetic disorder that includes sickle-cell anemia (the homozygous and most common form of SCD (SS)), sickle-cell hemoglobin C (SC) and sickle-cell β thalassemia (S/β thal) [1]. The protean clinical features of SCD result from chronic variable intravascular hemolysis and microvascular ischemia, leading to damage in multiple organs [2]. The occurrence of connective tissue diseases, in particular systemic lupus erythematosus (SLE), has only been rarely reported in patients with SCD [2]. The incidence of SLE in patients with SCD is not known because most of the published studies are case reports. Due to similar clinical manifestations, diagnosis of SLE in patients with SCD may be difficult and is often delayed. We report the case of a patient who developed symptoms initially attributed to SCD, but on further investigation underlying SLE was revealed.

Case presentation

A 23-year-old North-African woman with no family history of SCD was admitted to our department of internal medicine with symptoms of anemia, bone pain, arthralgia and fever. Her symptoms had been developing for six weeks with alteration of her general condition and abdominal pain. On physical examination our patient was pale, she had a temperature of 39.5°C, her blood pressure was 130/75mmHg and heart rate was 100 beats/minute. The patient had slight splenomegaly, pain on pressure in the long bones and arthritis in her knees.

Blood test results showed normocytic anemia at 6.6g/dL with a high reticulocyte count (230,000 cells/mm3), hyperleukocytosis with granulocytosis (leukocyte count 16,500 cells/mm3, polymorphonuclear cells 9500 cells/mm3) and moderate thrombopenia (100,000 cells/mm3). Further investigations showed diminished haptoglobin (0.08mg/L), elevated lactate dehydrogenase (4670UI/L) indirect hyperbilirubinemia (21mg/L) with moderate cytolysis and cholestasis (aspartate aminotransferase 43U/L, alanine aminotransferase 65U/L, phenylalanine ammonia lyase 217U/L and γ-glutamyl transpeptidase 188U/L). Hemoglobin (Hb) electrophoresis test results showed Hb S at 50.3 percent, Hb C at 44 percent and Hb A1 at 0 percent, confirming a diagnosis of SCD (hemoglobin S/C).

Our patient’s erythrocyte sediment rate was 110mm/first hour, her C-reactive protein level was 38mg/L (range <6mg/L), fibrinogen was 6.4g/L (24g/L) and serum protein electrophoresis showed a polyclonal IgG 24g/L (range 9 to 13g/L) with normal immunofixation. Results of a chest X-ray were normal. Abdominal ultrasonography, transthoracic and transesophageal echocardiography results were also normal. A thoraco-abdominal scan revealed numerous splenic infarctions. The results of a bone scan showed diffuse bone infarcts.

Her symptoms were attributed to SCD and hence our patient received blood transfusions, antibiotics and analgesics, but with no improvement. Her fever and arthritis failed to respond to this treatment. Instead, the evolution of her condition was marked by the development of arthritis in her hands and relapse of anemia.

Blood culture test results were negative, and the result of a tuberculin skin test was an 8mm induration. There was no BK virus found in repeated sputum and urine examinations, and procalcitonin test results were negative.

Serology test results for human immunodeficiency virus, hepatitis B, hepatitis C, brucellosis and typhoid fever were all negative. Cytobacteriological urine analysis revealed no bacteria but microscopic hematuria (670 cells/mm3) and leukocyturia (50 cells/mm3). Proteinuria results were negative.

The results of a Coombs test performed on admission were strongly positive for IgG. Immunological investigations revealed a positive anti-nuclear antibody (1/2600) result, and a positive anti-Sm result. Anti-DNA antibody tests were negative. A test for anti-extractable nuclear antigen antibodies (anti-ENA) was negative. C3 levels and C4 levels were normal (respectively, 0.95g/L and 0.3g/L). Tests for anti-phospholipid antibodies were negative. A diagnosis of SLE associated to SCD was established, with five of the diagnostic criteria of the American College of Rheumatology being met. Steroids were administered as a pulse of methylprednisolone 1g/day for three days followed by oral prednisone at 1mg/kg/day with hydroxychloroquine. Her symptoms quickly improved. At her 18-month follow up, she was in clinical remission on prednisone 5mg per day and hydroxychloroquine; she had not experienced a sickle-cell crisis and her lupus is still quiescent.

Discussion

In the present report we described the case of a Moroccan woman with SCD and coexistent SLE. The overlap of SLE and SCD is of interest, but the limited number of patients that have been reported previously implies that the association is uncommon [3]. Only 40 similar cases have been reported in the literature over the last 50 years [2-16] (Table 1). The African/Afro-Caribbean/African-American population is predisposed to contracting both SCD and SLE, explaining the fact that most patients with this association are African women (70 percent in Table 1 and 73 percent in the series by Michel et al.). All reported cases were relatively young at the time of lupus diagnosis (mean age 23 years, range eight to 57 years). All of them had SCD several years before SLE. Articular involvement is the most frequent lupus-related symptom, present in 84 percent of cases, followed by serositis (36 percent), and glomerulonephritis class III or IV (11 percent). Cutaneous manifestations are not frequently mentioned. Positive anti-nuclear antibody (ANA) results were found in 34 cases. Prognosis was favorable in 80 percent of cases (Table 1). Patients with SCD present with a defective activation of the alternate pathway of the complement system; this is the reason why these patients are at increased risk of capsulate bacteria infection, such as from pneumococci [15]. Some authors have suggested the hypothesis that this defect may lead to immune complex disorders secondary to failure to eliminate antigens, predisposing these patients to autoimmune diseases, but this has not been confirmed in other studies [3,11,13]. The clinical features of SLE and SCD have certain elements in common. Diverse manifestations such as polyarthritis, anemia, fever, visceral pain, renal, cardiovascular and pulmonary involvement are common in both conditions. Owing to the overlap of clinical features in the two diseases it may easy to confuse them, as occurred with our patient.

Table 1. Summary of previous case reports of SCD and SLE[2-16]

Further, the frequency and titers of antibodies in SCD have been reported as relatively higher than in population controls, making the diagnosis more challenging in clinical practice [17].

Toly-Ndour et al. reported that 50 percent of 88 patients with SCD had positive anti-nuclear antibody results and 20 percent had titers greater than one in 200, but only one patient developed rheumatoid arthritis five years later and no patients developed SLE [18]. In this series, patients treated with hydroxyurea had ANA-positive results less frequently than non-treated patients (P=0.053) [18].

Large prospective epidemiological studies are necessary to determine whether the prevalence of immune complex diseases is increased in patients with SCD.

Conclusions

This report illustrates the importance of considering associated diseases when clinical findings are unexplained by SCD alone, or are unresponsive to the conventional treatment. Early diagnosis and the initiation of appropriate treatment may decrease morbidity and mortality in these patients.

Consent

Written informed consent was obtained from the patient for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.

Competing interests

The authors declare that they have no competing interests.

Authors’ contributions

MM was the major contributor to the writing of the manuscript. ZTM reviewed the manuscript and prepared the final draft. HH and WM made substantial contributions to the acquisition and interpretation of clinical data and performed the literature research in PubMed. MAd and MAo gave final approval for the version to be published. All authors read and approved the final manuscript.

References

  1. Steinberg MH: Management of sickle cell disease.

    New Engl J Med 1999, 340:1021-1029. PubMed Abstract | Publisher Full Text OpenURL

  2. Michel M, Habibi A, Godeau B, Bachir D, Lahari A, Galacteros F, Fifi-Mah A, Arfi S: Characteristic and outcome of connective tissue diseases in patients with sickle cell disease: report of 30 cases.

    Semin Arthritis Rheum 2008, 38:228-240. PubMed Abstract | Publisher Full Text OpenURL

  3. Cherner M, Isenberg D: The overlap of systemic lupus erythematosus and sickle cell disease: report of two cases and a review of the literature.

    Lupus 2010, 19:875-883. PubMed Abstract | Publisher Full Text OpenURL

  4. Appenzeller S, Fattori A, Saad ST, Costallat TL: Systemic lupus erythematosus in a patient with sickle cell disease.

    Clin Rheumatol 2008, 27:359-364. PubMed Abstract | Publisher Full Text OpenURL

  5. Kanodia VK, Vanikar AV, Goplani KR, Gupta SB, Trivedi HL: Sickle cell nephropathy with diffuse proliferative lupus nephritis: a case report.

    Diagn Pathol 2008, 28:9. OpenURL

  6. Oqunbiyi AO, Geoge AO, Brown O, Okafor BO: Diagnostic and treatment difficulties in systemic lupus erythematosus coexisting with sickle cell disease.

    Westr Afr J Med 2007, 26:152-155. OpenURL

  7. Khalidi NA, Ajmani H, Varga J: Coexisting systemic lupus erythematosus and sickle cell disease. A diagnostic and therapeutic challenge.

    J Clin Rheumatol 2005, 11:86-92. PubMed Abstract | Publisher Full Text OpenURL

  8. Saxena VR, Mina R, Moallem HJ, Rao SP, Miller ST: Systemic lupus erythematosus in children with sickle cell disease.

    J Pediatr Hematol Oncol 2003, 25:668-671. PubMed Abstract | Publisher Full Text OpenURL

  9. Shetty AK, Baliga MR, Gedalia A, Warrier RP: Systemic lupus erythematosus and sickle cell disease.

    Indian J Pediatr 1998, 65:618-621. PubMed Abstract | Publisher Full Text OpenURL

  10. Pham TP, Lew SQ, Balow JE: Sickle cell nephropathy during the postpartum period in a patient with SLE.

    Am J Kidney Dis 1997, 30:879-883. PubMed Abstract | Publisher Full Text OpenURL

  11. Katsanis E, Hsu E, Luke KH, McKee JA: Systemic lupus erythematosus and sickle hemoglobinopathies: A report of two cases and review of the literature.

    Am J Hematol 1987, 25:211-214. PubMed Abstract | Publisher Full Text OpenURL

  12. Warrier RP, Sahney S, Walker H: Hemoglobin sickle cell disease and systemic lupus erythematosus.

    J Nate Med Assoc 1984, 76:1030-1031. OpenURL

  13. Luban NL, Boeckx RL, Barr O: Sickle cell anemia and SLE.

    J Pediatr 1980, 96:1120. PubMed Abstract OpenURL

  14. Karthikeyan G, Wallace SL, Blum L: SLE and sickle cell disease.

    Arthritis Rheum 1980, 21:862-863. OpenURL

  15. Wison WA, Nicholson GD, Hughes GR, Amin S, Alleyne G, Serjeant GR: Hemoglobin sickle cell disease and systemic lupus erythematosus.

    Br Med J 1976, 1:813. PubMed Abstract | Publisher Full Text | PubMed Central Full Text OpenURL

  16. Wilson FM, Clifford GO, Wolf PL: Lupus erythematosus associated with sickle cell anemia.

    Arthritis Rheum 1964, 7:443-449. PubMed Abstract | Publisher Full Text OpenURL

  17. Baethge BA, Bordelon TR, Mills GM, Bowen LM, Wolf RE, Bairnsfather L: Antinuclear antibodies in sickle cell disease.

    Acta Haematol 1990, 84:186-189. PubMed Abstract | Publisher Full Text OpenURL

  18. Toly-Ndour C, Rouquette AM, Obadia S, M’bappe P, Lionnet F, Hagege I, Boussa Khettab F, Tshilolo L, Girot R: High titers of autoantibodies in patients with sickle cell disease.

    J Rheumatol 2011, 38:302-309. PubMed Abstract | Publisher Full Text OpenURL