|Year : 2018 | Volume
| Issue : 3 | Page : 236-240
Cutaneous manifestations of juvenile onset lupus erythematosus: A clinical study
Vinitha Panicker1, Anil Mathew2, Gopikrishnan Anjaneyan1, Soumya Jagadeesan1, S. Lekshmi1, Jacob Thomas1
1 Department of Dermatology, Amrita Institute of Medical Sciences & Research Centre, Amrita Viswa Vidyapeetham, Kochi, Kerala, India
2 Department of Nephrology, Amrita Institute of Medical Sciences & Research Centre, Amrita Viswa Vidyapeetham, Kochi, Kerala, India
|Date of Web Publication||28-Jun-2018|
Dr. Anil Mathew
Department of Nephrology, Amrita Institute of Medical Sciences and Research Centre, Amrita University, Kochi, Kerala
Source of Support: None, Conflict of Interest: None
Introduction: Juvenile-onset systemic lupus erythematosus (SLE) is one of the most common systemic autoimmune connective tissue disorders in children. Studies focusing on the mucocutaneous manifestations of childhood lupus are scanty in literature. Objectives: This study was an attempt to describe the cutaneous changes seen in Pediatric Lupus and to correlate with the histopathological and immunofluoresecence findings. Methods: This was a retrospective study. All children under the age of 18 years who were diagnosed to have SLE according to the ACR criteria and presented to the dermatology outpatient department during a period of 1 year were included in the study. Details including clinical features, investigation findings including immunological tests and skin biopsy findings were noted. The analysis was performed using descriptive statistical tools such as percentage and frequency. Results: A total of 14 cases, average age at presentation was 10.14 years. Among the cutaneous manifestations, the most common presenting feature was urticarial vasculitis. Malar rash was seen in 57% of cases. Other cutaneous features seen were diffuse alopecia, oral ulcers. Antinuclear antibody was positive in all cases. Conclusion: Pediatric lupus tends to have a more aggressive course than adult lupus. Early diagnosis and treatment is necessary to prevent progression and development of complications.
Keywords: Juvenile-onset lupus, lupus band test, urticarial vasculitis
|How to cite this article:|
Panicker V, Mathew A, Anjaneyan G, Jagadeesan S, Lekshmi S, Thomas J. Cutaneous manifestations of juvenile onset lupus erythematosus: A clinical study. Indian J Paediatr Dermatol 2018;19:236-40
|How to cite this URL:|
Panicker V, Mathew A, Anjaneyan G, Jagadeesan S, Lekshmi S, Thomas J. Cutaneous manifestations of juvenile onset lupus erythematosus: A clinical study. Indian J Paediatr Dermatol [serial online] 2018 [cited 2019 Dec 12];19:236-40. Available from: http://www.ijpd.in/text.asp?2018/19/3/236/235493
| Introduction|| |
Juvenile-onset systemic lupus erythematosus (JSLE) is one of the most common systemic autoimmune connective tissue disorders in children. It is estimated that 15%–20% of SLE patients develop signs and symptoms during childhood and adolescence.,,
The incidence of JSLE across the world varies between 0.3 and 0.9/100,000 per year with estimated prevalence between 0.3 and 8.8/100,000. Females are more likely to be affected (male and female ratio; 1:3–1:5) with the peak age of presentation around puberty (median age onset was 12.1). In general, the disease in children follows a more aggressive course and need for prolonged treatment is frequent, which often leads to a greater incidence of therapy-related adverse effects. Studies focusing on the mucocutaneous manifestations of childhood lupus are scanty in literature. This study was an attempt to describe the cutaneous changes seen in pediatric lupus and to correlate with the histopathological and immunofluoresecence findings.
| Methods|| |
This was a retrospective chart review. All children under 18 years of age who were diagnosed to have SLE according to the ACR revised criteria (1982) and presented to the dermatology outpatient department during a period of 1 year were included in the study. The history, clinical examination including complete dermatological examination findings were noted in all cases. Relevant blood investigations, immunological workup, skin biopsy, and immunoflourescence findings were noted. A written informed consent was obtained from the parents of patients for the skin biopsy test.
| Results|| |
There were a total of 14 cases during the specified study period. The majority of the patients was females (78%). The average age of presentation was 10.14 years. The duration of disease varied from 6 months to 10 years, with average age was 3.6 years. The presenting cutaneous manifestation in majority of our cases was urticarial vasculitis 35% (5). Other presentations seen were generalized maculopapular rash (14%), palpable purpura (14%), discoid rash (7%), and alopecia areata (7%) [Table 1]. The cutaneous manifestations were divided into lupus erythematosus (LE)-specific and LE nonspecific. LE specific lesions seen were malar rash (57%) [Figure 1] and one case of discoid rash. No case of subacute cutaneous LE (SCLE) was encountered in our series. The LE nonspecific lesions seen were urticarial vasculitis (35%) [Figure 2], alopecia areata 7%, diffuse alopecia (100%), palpable purpura (14%), oral ulcers (21%), and bullous lesions (1 case) [Figure 3]. There was a history of photosensitivity in 35% of cases. Skin biopsy showed leukocytoclastic vasculitis (LCV) in majority of our patients (57%) [Figure 4] and [Figure 5] followed by interface dermatitis (14%). The lupus band [Figure 6] was positive in 92% (13/14). Another interesting feature noted in our series was a conspicuous absence of C3 in deposit in two cases which were diagnosed as hypocomplementemic urticarial vasculitis syndrome (HUVS). Complete blood picture showed anemia in 35%, leukopenia in 21%, and thrombocytopenia in 35%. Erythrocyte sedimentation rate (ESR) was elevated in all cases, mean ESR being 65.
|Figure 6: Direct immunofluorescence showing Ig deposition in basement membrane zone|
Click here to view
Immunology showed all our cases to be antinuclear antibody (ANA) positive, dsDNA positive in 85% (12 cases) and anti-Sm positivity 28%.
Among the systemic manifestation in our cases the most common was renal manifestations seen in 71% (10 cases). A renal biopsy was done in six cases, of which four cases showed proliferative lupus (class III in 2 cases, class IV in 2 cases). Other renal manifestations seen were microscopic hematuria and subnephrotic proteinuria. Other systemic manifestation seen was arthritis 64% (9 cases), hemolytic anemia 21% (3 cases), and pleural effusion 14% (2 cases).
| Discussion|| |
There is a significant variation in clinical manifestations in adult and pediatric lupus cases. Studies from Eastern and Northern India show that pediatric SLE has higher frequency of malar rash, renal manifestations, hematological, and neurological involvements than in adult SLE. On the other hand, photosensitivity and discoid skin lesions are prominent in adult SLE patients
The mean age of diagnosis in the present study was 10.14 years, similar results have been reported in a study from Iran. A study from India has reported the mean age of presentation to be 9.2 years.
Among the cutaneous manifestations, the most common presenting feature in our study was urticarial vasculitis (35%). The relationship of urticarial vasculitis with connective tissue diseases remains under investigation. It is known that only 2% of patients with the normo-complementemic form of the disease meet the criteria for SLE, whereas in the hypo-complementemic form, up to 50% of patients may have a defined overlapping syndrome. Urticarial vasculitis associated with pediatric lupus is rare and exact incidence is not known. However, urticarial vasculitis was associated with 6.6% in adult lupus according to an Indian study. The disparity in our study may be because our subjects were cases that presented with skin changes to the dermatologist and urticaria is one common reason for such patients seeking a dermatology consultation. Dubois mentioned that development of urticaria in a patient with SLE should lead the physician to carefully evaluate that patient for active systemic disease.
Another interesting feature noted in our series was a conspicuous absence of C3 in deposit in 2 cases which were diagnosed as HUVS. These 2 cases were of Arab origin and 1 had a strong family history of SLE. HUVS, or McDuffie syndrome, is a rare disease process that was first described by McDuffie et al. in 1973. Debate surrounds the pathophysiology of HUVS; however, low serum complement measurements in patients indicate the activation of the classical pathway, with low C1q, C4, and variably decreased C3 levels. Serum C1q precipitins were identified and later confirmed to be the autoantibodies against C1q (anti-C1q autoAbs). Diagnosis is confirmed by skin biopsy showing LCV and immunofluorescence showing the absence of C3 in deposits. HUVS is rarely reported in the pediatric population. We encountered two cases of this rare disease probably as this is a tertiary referral care center.
The LE specific lesions that we encountered were Malar rash and Discoid rash. In our case series, the most common type of LE-specific lesion was ACLE where 57% (8 patients) had Malar rash. Other studies have reported similar incidence-Vijay and Parveen, 68%, Thabet et al., 67.6%.
There was only 1 case of DLE and no cases of SCLE in our study.
Other studies have reported varying frequencies (chronic cutaneous LE - 45%, acute cutaneous LE - 34%, SCLE - 16%) Among the LE nonspecific lesions the most common encountered type was cutaneous vasculitis. In all patients with SLE, vasculitis has been reported in 10%–20%, and in children this is as high as 42%. Among vascular conditions the commonly encountered condition was urticarial vasculitis as already mentioned above and these cases showed LCV on skin biopsy. The incidence of urticarial vasculitis was 36% in our study and the overall incidence of vasculitis came up to 55% (including other cases of biopsy proven LCV). Other studies have reported 37.5% and 36%, respectively.,
Diffuse alopecia was seen in all our cases at some point of time. The study by Vijay and Parveen has reported 25% incidence of alopecia. We also encountered a case of a 4 year old child who presented with alopecia areata who on routine workup was found to be ANA and dsDNA positive and diagnosed with SLE. Alopecia areata as a presenting symptom of SLE has not been previously reported in literature and was a unique finding in our case series.
There was one case of bullous disease in our study which was a case who presented with vesicles and bullae in perioral area, abdomen, forearm, and palpable purpura on both legs. Skin biopsy from the vesicle showed subepidermal split and direct immunofluorescence showed linear IgA along EBM. Skin biopsy from palpable purpura showed interface dermatitis with LCV. This case was diagnosed as a case of SLE associated with LABD. This has been previously reported in literature.
The presence of ANA in the serum of our patients was detected in all patients (100%). A similar frequency of ANA was also found in many other studies.,, Anti-dsDNA and anti-Sm are the specific antibodies for diagnosis of SLE. Our cases showed 85% dsDNA positivity, almost similar frequency were detected in other studies.,, Anti-Sm positivity in our series was 28%, varying results have been noted in various studies Vijay and Parveen reported 12.5% whereas Thabet et al., reported higher incidence 56.8%, the fluctuation in results could be due to different ethnic origins of these patients.
Although the classical feature of skin biopsy in SLE is interface dermatitis we had only 2 cases showing the same in accordance with clinical presentation as only 2 cases presented with generalized maculopapular rash which was probably a generalized ACLE.
The most common skin biopsy finding in our study was LCV which was encountered in 57% of cases which was concordant with clinical presentation as these cases were either clinically having urticarial lesions or palpable purpura.
Direct immunofluorescence (DIF) is a valuable diagnostic auxiliary to histopathology. In our study, lupus band test was positive in 93.8% (13 cases). There is still to date considerable controversy as to the diagnostic and prognostic value of the lupus band test; however, if it is conducted with skin collected from the nonlesional area that is totally protected from the sun, such as the gluteal region or the internal surface of the upper portion of the arm, a positive result with the presence of three or more classes of immunoglobulins or complement has high specificity for SLE.
Smith et al., compared DIF findings for normal skin from the deltoid region of 102 patients with SLE and 151 with a range of other rheumatic diseases, found IgM deposits at the dermal-epidermal junction (DEJ), particularly among those with other rheumatic diseases. They concluded that the nature and number of proteins found at the DEJ are important determinants for the specificity and predictive value for a diagnosis of LE. A finding of a single protein, especially IgM, at the DEJ, is of little diagnostic value for SLE.
The most common systemic manifestation in our series was renal involvement (71%) similar results have been observed by Thabet et al. Other studies have reported 52%, 56%, and 50%, respectively.
| Conclusion|| |
Childhood lupus generally tends to have a more aggressive course than adult lupus. Cutaneous manifestation may be the presenting feature in many cases so a high index of suspicion is necessary for diagnosis as early diagnosis and treatment may prevent further progression of the disease.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given her consent for her images and other clinical information to be reported in the journal. The patient understand that her name and initial will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Jiménez S, Cervera R, Font J, Ingelmo M. The epidemiology of systemic lupus erythematosus. Clin Rev Allergy Immunol 2003;25:3-12.
Ramírez Gómez LA, Uribe Uribe O, Osio Uribe O, Grisales Romero H, Cardiel MH, Wojdyla D, et al.
Childhood systemic lupus erythematosus in Latin America. The GLADEL experience in 230 children. Lupus 2008;17:596-604.
Harvey AM, Shulman LE, Tumulty PA, Conley CL, Schoenrich EH. Systemic lupus erythematosus: Review of the literature and clinical analysis of 138 cases. Medicine (Baltimore) 1954;33:291-437.
Hiraki LT, Benseler SM, Tyrrell PN, Harvey E, Hebert D, Silverman ED, et al.
Ethnic differences in pediatric systemic lupus erythematosus. J Rheumatol 2009;36:2539-46.
Pradhan V, Patwardhan M, Rajadhyaksha A, Ghosh K. Clinical and immunological profile of systemic lupus erythematosus. Indian Pediatr 2013;50:405-7.
Alyasin S, Amin R, Moghtaderi M, kashef S. Childhood-onset systemic lupus erythematosus in Southwestern Iran: A clinical and serological study. Arch Rheumatol 2014;29:167-70.
Kole AK, Ghosh A. Cutaneous manifestations of systemic lupus erythematosus in a tertiary referral center. Indian J Dermatol 2009;54:132-6.
] [Full text]
Dubois EL. Clinical picture of systemic lupus erythematosus. Lupus Erythematosus. Los Angeles: University of Southern California Press; 1974. p. 294-5.
McDuffie FC, Sams WM Jr., Maldonado JE, Andreini PH, Conn DL, Samayoa EA, et al.
Hypocomplementemia with cutaneous vasculitis and arthritis. Possible immune complex syndrome. Mayo Clin Proc 1973;48:340-8.
Zeiss CR, Burch FX, Marder RJ, Furey NL, Schmid FR, Gewurz H, et al.
Ahypocomplementemic vasculitic urticarial syndrome. Report of four new cases and definition of the disease. Am J Med 1980;68:867-75.
Balsam L, Karim M, Miller F, Rubinstein S. Crescentic glomerulonephritis associated with hypocomplementemic urticarial vasculitis syndrome. Am J Kidney Dis 2008;52:1168-73.
Vijay Y, Parveen B. Clinical and immunological profile of systemic lupus erythematosus in a pediatric population in North India. Egypt Rheumatol Rehabil 2014;41:148-14. [Full text]
Thabet Y, Mankaï A, Achour A, Sakly W, Trabelsi A, Harbi A, et al
. Systemic lupus erythematosus in children: A study about 37 Tunisian cases. J Clin Cell Immunol 2014;5:192.
Dickey BZ, Holland KE, Drolet BA, Galbraith SS, Lyon VB, Siegel DH, et al.
Demographic and clinical characteristics of cutaneous lupus erythematosus at a paediatric dermatology referral centre. Br J Dermatol 2013;169:428-33.
Wananukul S, Watana D, Pongprasit P. Cutaneous manifestations of childhood systemic lupus erythematosus. Pediatr Dermatol 1998;15:342-6.
Lee HJ, Yun SJ, Lee SC, Lee JB. A case of linear IgA bullous dermatosis associated with systemic lupus erythematosus. Ann Dermatol 2016;28:660-2.
Sontheimer RD. Clinical manifestations of cutaneous lupus erythematosus. In: Wallace DJ, Hahn BH, editors. Dubois' Lupus Erythematosus. Pennsylvania: Lea & Febiger; 1993. p. 285-301.
Smith CD, Marino C, Rothfield NF. The clinical utility of the lupus band test. Arthritis Rheum 1984;27:382-7.
[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6]