July 2013, Volume 63, Issue 7

Original Article

Lupus, still a mystery: A comparison of clinical features of Pakistani population living in suburbs of Karachi with other Asian countries

Muhammad Ishaq  ( Department of Medicine, Jinnah Medical College Hospital, Karachi, Pakistan. )
Lubna Nazir  ( Department of Medicine, Jinnah Medical College Hospital, Karachi, Pakistan. )
Saera Sohail Kidwai  ( Department of Medicine, Jinnah Medical College Hospital, Karachi, Pakistan. )
Amir Riaz  ( Liaquat National Hospital, Karachi, Pakistan. )
Wahid Haroon  ( Al-Hamra Diabetes Center, Karachi, Pakistan. )
Shaista Siddiqi  ( Department of Neurology, Jinnah Medical College Hospital, Karachi, Pakistan. )

Abstract

Objective: To determine the presenting features of patients with systemic lupus erythematosus at a private hospital in Karachi, and to compare the features with those of other Asian populations.
Methods: The retrospective study comprised records of all lupus cases meeting the revised American Rheumatism Association criteria at the time of presentation at Jinnah Medical College Hospital, Karachi, from May 2008 to June 2011. Demographic and clinical data was analysed using SPSS 11.5.
Results: Of the 105 cases in the study, there were 6 (5.7%) males and 99 (94.3%) females, with a male-to-female ratio of 1:16 and a mean age of 31.6±10.5 years. Clinical manifestations included: constitutional symptoms in (n=69; 65.7%), arthropathy (n=81; 77%), cutaneous involvement (n=39; 37%), lupus nephritis (n=24; 22.8%), pleurisy (n=9; 8.6%), Raynaud\\\'s phenomenon (n=24; 22.8%), and vasculitis (n=18; 17%). One (0.95%) patient presented with mononeuritis multiplex, and 1 (0.95%) with acute pancreatitis.
Conclusion: The diversity in clinical presentation appeared to be a reflection of the great variability that exists among Asian countries with regards to their genetic, environmental and socio-demographic backgrounds. The differences also existed in our own population, suggesting some unknown etiology.
Keywords: Systemic Lupus erythematosus, Autoimmune disease, Vasculitis, Livedo Reticularis, Arthritis. (JPMA 63: 869; 2013).

Introduction

Systemic lupus erythematosus (SLE) is an autoimmune disease — a type of self-allergy — whereby the patient\\\'s immune system creates antibodies that attack the person\\\'s own body tissues instead of protecting the body from bacteria and viruses.1
Asia is the largest continent in terms of area it covers and consists of a population around 4 billion. It has diverse ethnic distribution with Orientals in the east, Indians in the south, Arabs in the Middle East, and Russians in north Asia.
There is varying epidemiological information regarding SLE among Asian countries. Prevalence rates usually fall within 30-50/100,000 population. Incidence rates, as reported from a few countries, vary from 0.9/100,000 to 3.1% per annum. It is difficult to make generalisations about how the epidemiological character of the disease varies from country to country. However, similarities in disease manifestations can be observed.2 SLE is a complicated disease, as no patient presents with the same set of symptoms. This could be due to the surrounding environment, such as the climate, where sunlight plays a role in photosensitivity and skin rashes, or a colder climate could onset complications such as Raynaud\\\'s phenomenon.3
The aim of the current study was to determine the most common symptoms and complications of patients with SLE admitted at a private hospital in Karachi, and to compare these features with other Asian populations.

Materials and Methods

The retrospective study comprised records of all SLE cases meeting the revised American Rheumatism Association (ARA) criteria4 for lupus at the time of presentation at Jinnah Medical College Hospital, Karachi, from May 2008 till June 2011. Demographic and clinical data of all the patients was recorded. Statistical analysis was done using SPSS 11.5.

Results

Of the 105 cases in the study, 6 (5.7%) were males and 99 (94.3%) were females, with a male-to-female ratio of 1:16 and a mean age of 31.6±10.5 years. Nine (8.5%) patients were above 50 years of age. The most common presenting clinical manifestations were constitutional symptoms in 69 (65.7%), arthropathy in 81 (77%) and cutaneous involvement in 39 (37%) (Table-1).


There were 24 (22.8%) patients with lupus nephritis which was mainly glomerulonephritis, while 3 (2.8%) patients presented with full-blown nephrotic syndrome at the time of diagnosis
Neurological involvement included psychosis in 6 (5.7%), headache in 2 (1.90%) while 8 (7.6%) presented with seizures. None had focal neurological deficit at the time of presentation. One (0.9%) patient presented with mono-neuritis multiplex having bilateral wrists and unilateral foot drop and livedo reticularis in distal upper and lower limbs.
Gastro-intestinal symptoms were seen in 9 (8.6%) patients which mainly presented as anorexia, nausea and vomiting. One (0.9%) patient presented with acute abdominal pain and had malar rash, arthritis, alopecia and oral ulcers. Her serum amylase was elevated 10 times from normal and was diagnosed with SLE-induced acute pancreatitis after ruling out alcohol, gall stones or metabolic causes as potential reasons. She was given methylprednisolone followed by oral corticosteroid, with her lipase level falling after 5 days of treatment with complete resolution to normal levels in 4 weeks during which she continued with 1mg/kg dose of prednisolone with recovery of all other symptoms.
The presenting manifestations were compared with other Asian populations (Table-2).

Discussion

Our data included clinical features present at the time of SLE diagnosis, while most of the other studies have focussed on clinical manifestations throughout the course of SLE.
Female-to-male ratio varied in different studies, but all had a female preponderance. This could be due to hormonal factors and the fact that females of many mammalian species offer higher antibody responses than the males.5
There appeared to be similarities, with most of the common features, including articular and muco-cutaneous involvement.
Most people with SLE had intermittent polyarthritis, varying from mild to disabling and characterised by soft tissue swelling and tenderness in the joints.5 Joint symptoms were the most common presenting feature in the study, but none of the patients had joint deformity or X-ray evidence of joint erosion. The frequency of articular involvement was almost comparable to the Asian data.6-11 Dermal involvement was observed in 37% patients which is similar to an Indian study12 of 150 SLE patients in which 30% had skin involvement at the time of presentation which increased to 100% as the disease progressed. In our study, malar rash was the most common dermal presentation seen in 37% patients, whereas other studies have reported malar rash in 49%13 and 53.18%14 of their patients. Non-scarring alopecia was seen in 30%, while only 2 patients presented with scarring alopecia. Discoid lesions were seen in 8.5% cases, which more or less corroborated with an Indian study.12 A low incidence of photosensitivity was observed in our patients (7.6%) compared to the majority of Asian studies6-10,15,16 which may be partly explained by lower exposure of our patients to sunlight as per traditional covering of face practised in our country. Two patients in our study presented with Livedo reticularis spread on arms and legs. Livedo reticular is also rare and none of the 150 patients in an Indian study12 presented with this dermal problem.
In contrast to a Saudi7 study where a significant number of patients had pericarditis (20.8%) and pleuritis (15.9%), our study revealed that 8.6 % patient presented with pleurisy while none had pericarditis. Most of the other Asian studies did not mention this complication.
In our study, the presentation of patients who had peripheral vasculitic lesions (17%), ranged from nail fold infarcts to gangrene of toes; all of them also had Raynaud\\\'s phenomenon. The overall frequency of Raynaud\\\'s phenomenon in our study was 22.8 % compared to the Saudi study in which it was only 8.7%, whereas a study from north India17 noted Raynaud\\\'s phenomenon in 32%. This variation may be attributable to the regional climatic condition.12
The frequency of neurological involvement was similar to Filipino6 and Chinese18 studies which reported very low numbers compared to India9 where up to 50% of SLE patients had neurological involvement. Mononeuritis multiplex is rare in SLE. In 518 Chinese18 SLE patients, the frequency of mononeuritis multiplex was only 1.5%, making it a rare presentation. Data from other Asian countries on this count was unavailable.
Lupus nephritis, which was mainly glomerulonephritis, was present in 22.8% of our patients, while three patients presented with full-blown nephrotic syndrome at the time of diagnosis. This frequency is the lowest when compared to other Asian6 populations, which may be because they took into account the features present during the course of the illness rather than at the time of diagnosis alone.
Gastrointestinal manifestations of SLE included mouth ulcers, dysphagia, anorexia, nausea, vomiting, haemorrhage and abdominal pain. The frequency was comparable to an Iranian study8 (8.6% vs. 8.3%). Pancreatitis is a rare complication of SLE .The association between SLE and pancreatitis was first documented in 1939.19 Since then, few cases have presented with pancreatitis as an initial manifestation, with fewer reporting from Asia.20,21 Theories regarding pathogenesis of pancreatitis in SLE include pancreatic vascular events (thrombosis and vasculitis), inspissated secretions attributed to corticosteroids and necrotising pancreatitis. Hypothetical mechanisms include complement activation, hypotension and pancreatic antibodies.22
Constitutional symptoms were the most common presentation and included the presence of fever, malaise, anorexia and weight-loss. Of our patients, 65.7% presented with constitutional symptoms, which is less than that reported by a recent Pakistani study23 in which 100% patients had fever as the presenting feature. Compared to that study, we also found a lower frequency of articular involvement (77% vs. 98%), dermal involvement (37% vs. 64%) and mucosal involvement (22.8% vs. 58%). This difference of presentation in the same region and same ethnic group signifies that SLE is a disease with many manifestations, and each person\\\'s profile or list of symptoms is different.1

Conclusion

Clinical characteristics of SLE patients in Pakistan are not always in line with other Asian races. The diversity appears to be a reflection of the great variability that exists between these populations with regards to their genetic, environmental and socio-demographic backgrounds. This difference also exists within our own population, suggesting some unknown etiology.

References

1. What is Lupus? (Online) The Lupus Site.  (Cited 2009 November 2). Available from URL: http://www.thelupussite.com/lupus1.html.
2. Osio-Salido E, Manapat-Reyes H. Epidemiology of systemic lupus erythematosus in Asia. Lupus 2010; 19: 1365-73.
3. Carey R, Simmons S, Malherbe M, van Rensburg JJ, Joubert G. Clinical features of patients with Systemic Lupus Erythematosus (SLE) patients attending the SLE outpatient clinic at Universitas Hospital in Bloemfontein, SA. SA Fam Pract 2008; 50: 68.
4. Petri M, Orbai AM, Alarcon GS, Gordon C, Merrill JT, Fortin PR, et al. Derivation and validation of the Systemic Lupus International Collaborating Clinics classification criteria for systemiclupus erythematosus. Arthritis Rheum 2012; 64: 2677-86.
5. Hahn BH. Systemic lupus erythematosus. In: Longo DL, Fauci AS, Kasper DL, Hauser SL, Jameson JL, Loscalzo J (eds.). Harrison\\\'s Principles of Internal Medicine, Vol. 2. 18th ed. New York: McGraw-Hill; 2012; pp 2724-6.
6. Villamin CA, Navarra SV. Clinical manifestations and clinical syndromes of Filipino patients with systemic lupus erythematosus. Mod Rheumatol 2008; 18: 161-4.
7. Al Arfaj AS, Khali N. Clinical and immunological manifestations in 624 SLE patients in Saudi Arabia. Lupus 2009; 18: 465-73.
8.  Nazarinia MA, Ghaffarpasand F, Shamsdin A, Karimi AA, Abbasi N, Amiri A. Systemic lupus erythematosus in the Fars Province of Iran. Lupus 2008; 17: 221-7.
9. Malaviya AN, Chandrasekaran AN, Kuamr A, Sharma PN. Systemic lupus erythematosus in India. Lupus 1997; 6: 690-700.
10. Mok CC, Lau CS. Lupus in Hong Kong Chinese. Lupus 2003; 12: 717-22.
11. Chun BC, Bae SC. Mortality and cancer incidence in Korean patients with systemic lupus erythematosus: results from the Hanyang lupus cohort in Seoul, Korea. Lupus 2005; 14: 635-8.
12. Kole AK, Ghosh A. Cutaneous manifestations of systemic lupus erythematosus in a tertiary referral center. Indian J Dermatol 2009; 54: 132-6.
13. Wysenbeek AJ, Guedj D, Amit M, Weinberger A. Rash in SLE: prevalence and cutaneous and non-cutaneous disease manifestations. Ann Rheum Dis 1992; 51: 717-9.
14.  Vaidya S, Samant RS, Nadkar MY, Borges NE. Systemic lupus erythematosus - review of two hundred and twenty patients. J India Rheumatol Assoc 1997; 5: 14-8.
15. Boey ML. Systemic lupus erythematosus in Singapore. Ann Acad Med Singapore 1998; 27: 35-41.
16. Wang F, Wang CL, Tan CT, Manivasagar M. Systemic lupus erythematosus in Malaysia: a study of 539 patients and comparison of prevalence and disease expression in different racial and gender groups. Lupus 1997; 6: 248-53.
17. Malaviya AN, Singh RR, Kumar A, De A, Kumar A, Aradhye S. Systemic lupus erythematosus in northern India: a review of 329 cases. J Assoc Physicians India 1988; 36: 476-80, 484.
18. Mok CC, Lau CS, Wong RW. Neuropsychiatric manifestations and their clinical associations in southern Chinese patients with systemic lupus erythematosus. J Rheumatol 2001; 28: 766-71.
19. Reifenstein EC, Reifenstein EC Jr, Reifenstein GH. A variable symptom complex of undetermined etiology with fatal termination: including conditions described as visceral erythema group (Osler), disseminated lupus erythematosus, atypical verrucous endocarditis (Libman-Sacks), fever of unknown origin (Christian) and diffuse peripheral vascular disease (Baehr and others). Arch Intern Med 1939; 63: 553-74.
20. Singh M, Wari S, Murtaza M, Joglekar S, Kasubhai M. Systemic lupus erythematosus presenting with acute fatal pancreatitis as an initial manifestation. Am J Gastroenterol 2001; 96: 2280-1.
21. Kobayashi S, Yoshida M, Kitahara T,  Abe Y,  Tsuchida A, Nojima Y. Autoimmune pancreatitis as the initial presentation of systemic lupus erythematosus. Lupus 2007; 16: 133-6.
22. Petri M. Pancreatitis in systemic lupus erythematosus: still in search of a mechanism. J Rheumatol 1992; 19: 1014-6.
23. Ahmed TA, Ikram N, Hussain T, Farooqui A, Haleem A, Bashir M, et al. Clinical and laboratory features of Systemic Lupus Erythematosus (SLE) in Pakistani patients. J Pak Med Assoc 2002; 52: 12-5.

Journal of the Pakistan Medical Association has agreed to receive and publish manuscripts in accordance with the principles of the following committees: