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 Table of Contents  
ORIGINAL ARTICLE
Year : 2019  |  Volume : 21  |  Issue : 2  |  Page : 170-176

A study of dermatological manifestations in patients attending the rheumatology outpatient department at a tertiary care hospital


1 Department of Dermatology, Armed Forces Medical College, Pune, Maharashtra, India
2 DGMS(Air) and Prof (Dermatology), o/o DGMS(Air), New Delhi, India
3 Department of Med and Rheumatology, Sri Balaji Medical College and Hospital, Chennai, Tamil Nadu, India
4 Department of Dermatology, INHS Asvini, Mumbai, Maharashtra, India
5 Department of Community Medicine, Armed Forces Medical College, Pune, Maharashtra, India
6 Department of Radiodiagnosis, Armed Forces Medical College, Pune, Maharashtra, India

Date of Submission21-Nov-2018
Date of Acceptance05-Jun-2019
Date of Web Publication07-Oct-2019

Correspondence Address:
Lt Col (Dr) Preema Sinha
Department of Dermatology, Armed Forces Medical College, Pune, Maharashtra
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jmms.jmms_72_18

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  Abstract 


Background: Autoimmune processes commonly involve skin along with the musculoskeletal system, resulting in inflammatory diseases characterized by concurrent mucocutaneous and rheumatic manifestations. Aim: We undertook a clinical study to assess the pattern, type, extent, severity, and morphology of dermatological manifestations in rheumatology patients, to analyze the correlation of dermatoses observed with the type of rheumatological disorder, and to look for the side effects of drug therapy including disease-modifying antirheumatic drugs. Materials and Methods: A cross-sectional descriptive study carried out in the outpatient department (OPD) setting of 100 patients, having joint and/or bone involvement associated with cutaneous disorders, attending rheumatology OPD of a tertiary care hospital were included and followed up for 6 months to assess the mucocutaneous manifestations. Patients with no cutaneous manifestations were excluded from the study. Statistical analysis was done using STATA 13 IC. Results: Papulosquamous skin lesions (45%) were the most common dermatological manifestations in the study, followed by nail changes (30%), photosensitivity (20%), Raynaud's phenomenon (17%), and malar rash (15%). Drug-induced cutaneous features were seen in 18% of patients. Cutaneous manifestations were seen most commonly in the connective tissue diseases group (55%), followed by seronegative arthritis (34%), rheumatoid arthritis (8%), and erythema nodosum (3%). Frequently affected age group was 31–40 years (41%), followed by 41–50 years (23%) of age group. The most common therapeutic interventions causing cutaneous side effects were systemic steroids. Conclusions: Many patients attending the rheumatology OPD present with varied mucocutaneous manifestations, and they can also develop numerous drug-related cutaneous side effects once started on antirheumatic medications. Hence, a collaborative clinic between a rheumatologist and a dermatologist is a necessity which will help in holistic patient management and disease remission.

Keywords: Antirheumatic drugs, connective tissue disorders, mucocutaneous lesions, mucocutaneous side effects, psoriatic arthritis, rheumatology outpatient department


How to cite this article:
Sinha P, Grewal RS, Shanmuganandan K, Chatterjee M, Yadav AK, Bhattacharjee S. A study of dermatological manifestations in patients attending the rheumatology outpatient department at a tertiary care hospital. J Mar Med Soc 2019;21:170-6

How to cite this URL:
Sinha P, Grewal RS, Shanmuganandan K, Chatterjee M, Yadav AK, Bhattacharjee S. A study of dermatological manifestations in patients attending the rheumatology outpatient department at a tertiary care hospital. J Mar Med Soc [serial online] 2019 [cited 2019 Dec 9];21:170-6. Available from: http://www.marinemedicalsociety.in/text.asp?2019/21/2/170/268631




  Introduction Top


Commonly encountered rheumatological disorders are lupus erythematosus, scleroderma, dermatomyositis, rheumatoid arthritis, Still's disease, Sjögren's syndrome, mixed connective tissue diseases, and psoriatic arthritis. They often present with concurrent mucocutaneous and rheumatic manifestations.[1] In addition, many of the antirheumatic drugs used can give rise to cutaneous side effects. A lot of patients presenting with features such as photosensitivity, malar rash, papulosquamous skin lesions, and oral ulcers require a cohesive collaboration between a dermatologist and a rheumatologist for effective intervention in these cases. Hence, a thorough knowledge of the dermatological manifestations of these diseases as well as side effects of commonly administered drugs in these patients is useful for their diagnosis, management, and follow-up and for assessing prognosis. We conducted a study to describe the pattern, type, extent, severity, and morphology of the various dermatological manifestations in rheumatology patients and the cutaneous side effects of therapy including disease-modifying antirheumatic drugs.


  Materials and Methods Top


The study design was a cross-sectional descriptive study conducted at the outpatient department (OPD) of the rheumatology center of a tertiary care teaching hospital. Ethical approval of the institutional ethical committee was obtained. The sample size was calculated based on the following assumption: the prevalence of dermatological manifestation as 50%, the precision of 10%, and for a 95% confidence interval, the calculated sample size comes out to be 96. However, it was decided to include 100 cases in our study. The cases were chosen using systematic random sampling of cases with rheumatological disorders, having joint and/or bone involvement associated with cutaneous disorders, and attending the rheumatology OPD who were followed up for 6 months to assess the mucocutaneous side effects. Patients attending the rheumatology OPD with no cutaneous manifestations were excluded from the study.

A detailed history (including mode of presentation, course of the disease, and relevant details of family and treatment history) was recorded in each case. A complete history regarding the time of onset of skin lesions, extent of involvement, and progression was taken. A thorough general, systemic, musculoskeletal, and dermatological examination was carried out in each case. Dermatological lesions, including those of mucosae, hair and nails, and genitalia, were examined with regard to their morphology, arrangement, distribution, color, consistency, configuration, edge, surface, and sequelae. Detailed examination of the skeletal system was carried out in all cases, and a photographic record was maintained. Patients were followed up for 6 months to assess any mucocutaneous side effect of therapy. Each case was investigated to establish the diagnosis and elucidate the type and degree of dermatological involvement. Baseline investigations and specific investigations such as uric acid, C-reactive protein, creatine phosphokinase, skin biopsy, nail fold capillaroscopy, rheumatoid factor, antinuclear antibody profile, enzyme-linked immunosorbent assay for HIV, barium swallow, and pulmonary function tests were done were done wherever relevant while using evaluation criteria like the SLICC criteria for lupus erythematosus and the CASPAR criteria for psoriatic arthritis. Disease activity was measured by the systemic lupus erythematosus disease activity index (SLEDAI) in the lupus group and tender joint count for psoriatic arthritis group.

Results were analyzed using StataCorp. 2013. Stata: Release 13 IC. Statistical Software. College Station, TX, USA: StataCorp LP. All categorical variables were analyzed using number and percentages and provided with 95% confidence interval. Chi-square or its variant was used for the association between two categorical variables. A P < 0.05 is considered statistically significant.


  Results Top


In our study, dermatological manifestations were most common in the connective tissue group (55%), followed by seronegative arthritis (34%), rheumatoid arthritis (8%), and erythema nodosum (3%). The sex distribution is given in [Table 1]. The most frequently affected age group was 31–40 years (41%), followed by 41–50 years (23%). The youngest patient was 14 years old and the oldest was 62 years old. Overall, papulosquamous skin lesions (45%) [Figure 1] were the most common cutaneous manifestations in the study, followed by nail changes (30%), photosensitivity (20%), Raynaud's phenomenon (17%), and malar rash (15%).
Table 1: Distribution of cases in males and females

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Figure 1: Papulosquamous lesions over the back in a patient of systemic lupus erythematosus

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Among connective tissue disorders, lupus erythematosus was the single largest disease with mucocutaneous manifestations (65.45%) [Table 2]. The most common cutaneous feature observed in the lupus erythematosus group was photosensitivity 27/36 (75%), followed by discoid rash 15/36 (41.66%), papulosquamous lesions 12/36 (33.33%), and Raynaud's phenomenon in 10/36 (27.7%) of the patients. Nonscarring alopecia 5/36 (13.88%) and malar rash 10/36 (27.77%) [Figure 2] were seen in patients with acute lupus erythematosus with high SLEDAI scores denoting relation to disease activity. One case of lupus profundus was also seen, which is a rare presentation.
Table 2: Connective tissue diseases' distribution of cases (n=55)

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Figure 2: Malar rash in a patient of lupus erythematosus

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Among the six patients of dermatomyositis, the most common skin manifestations included heliotrope rash, malar erythema, and dyspigmentation 5/6 (83.33% each), followed by Gottron's sign, Gottron's papule, and periungual telangiectasias 4/6 (66.66% each) [Figure 3]. Calcinosis was found in the case of juvenile dermatomyositis.
Figure 3: Gottron's sign in a patient of dermatomyositis

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All 6/6 (100%) of our cases of systemic sclerosis had a history of Raynaud's phenomenon and showed features of sclerodactyly and digital pitted scars and also all had mask-like facies with microstomia [Figure 4]. 4/6 (66.66%) had nail fold telangiectasias and 2/6 (33.33%) patients showed salt and pepper pigmentation over the extremities. Among five patients of localized scleroderma examined, two had plaque morphea, one had generalized morphea, one was with linear morphea, and one had Parry–Romberg syndrome.
Figure 4: Raynaud's phenomenon in the case of systemic sclerosis

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The patient of mixed connective tissue disorder had cutaneous manifestations in the form of sclerodactyly, cutaneous ulcerations, Raynaud's phenomenon, and microstomia. Only one patient had secondary Sjögren's syndrome, and she had cutaneous manifestations in the form of generalized xerosis, xerostomia, and dry eyes.

All patients of psoriatic arthropathy had cutaneous involvement in the form of psoriatic plaques, with predominant involvement of 27/31 (87.09%) scalp [Figure 5]. 90.32% of these patients had nail involvement in the form of pitting, distal onycholysis, subungual hyperkeratosis, discoloration, and nail crumbling [Figure 6]. One lady with facial lesions had severe deforming arthritis, with the onset of arthritis 5 years before the onset of cutaneous lesions.
Figure 5: Scalp involvement in a patient of psoriasis vulgaris

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Figure 6: Nail involvement in a patient of psoriasis vulgaris in the form of nail pitting and distal onycholysis

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Both patients of Reiter's disease had psoriasiform skin lesions, circinate balanitis, keratoderma blenorrhagicum, and severe nail involvement.

The solitary patient with Behcet's disease had cutaneous findings in the form of oral ulcerations and papulopustular lesions. Tender erythematosus nodules were present in both patients of erythema nodosum.

Among eight patients of rheumatoid arthritis evaluated, only one had rheumatoid nodules 1/8 (12.5%). One lady had rheumatoid vasculitis 1/8 (12.5%) and she expired 3 months after developing the vasculitic lesions [Figure 7].
Figure 7: Vasculitic lesions in a case of rheumatoid arthritis

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[Table 3] shows the complete details of all cutaneous features observed in the study population.
Table 3: Cutaneous features observed in the study population (n=100)

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The drugs exhibited to these 100 study patients included nonsteroidal anti-inflammatory drugs (NSAIDs) (38%), methotrexate (32%), oral corticosteroids (23%), leflunomide (4%), antimalarials (34%), dapsone (2%), tumor necrosis factor (TNF)-alpha inhibitors (3%), and intravenous immunoglobulin (1%). In the 6-month follow-up, mucocutaneous side effects were observed in only patients treated with systemic corticosteroids (17/23, 73.91%) and leflunomide (1/4, 25%). The commonly observed side effects due to oral corticosteroids included dermatophytosis 6/23 (26.08%), cushingoid habitus 5/23 (21.73%), acneiform eruptions 4/23 (17.39%), onychomycosis 1/23 (4.34%), and vulvovaginal candidiasis 1/23 (4.34%) [Figure 8] and [Figure 9]. Leflunomide-induced erythema multiforme was observed in one patient of rheumatoid arthritis.
Figure 8: Cushingoid habitus in the form of moon facies in a case of systemic lupus erythematosus; also seen are the characteristic palatal ulcers of systemic lupus erythematosus in the same patient

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Figure 9: Tinea cruris with secondary infection in a patient of systemic lupus erythematosus

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  Discussion Top


Rheumatological disorders often have mucocutaneous manifestations, and sometimes, skin lesions are the initial or most problematic manifestation of a patient's disease. Many of the skin lesions encountered in these disorders are rather nonspecific. Other lesions, however, have characteristic and sometimes specific findings that often help a clinician to diagnose the underlying rheumatic disease process. In addition, drug-induced skin lesions are often encountered in patients being treated for rheumatic disease.[1],[2]

Our descriptive study is unique as till date we do not find similar studies in the literature. This study tells us the relevance of dermatological examination of patients attending the rheumatology OPD as patients with disease activity can be picked up early as well as vigilant screening for cutaneous side effects of these commonly used drugs can also be done in them.

[Table 1] denotes sex distribution seen in our study; it had more female patients suffering from connective tissue diseases and rheumatoid arthritis. Studies by Sontheimer et al. and Costner et al. gave similar distribution.[1],[2]

In the present study, the maximum number of patients with cutaneous manifestations attending the rheumatology OPD belonged to the connective tissue group (55%), followed by seronegative arthritis (34%), rheumatoid arthritis (8%), and erythema nodosum (3%). Overall, papulosquamous skin lesions (45%) were the most common cutaneous manifestations in the study, followed by nail changes (30%), photosensitivity (20%), Raynaud's phenomenon (17%), and malar rash (15%). Papulosquamous lesions are seen both in psoriasis and subacute lupus erythematosus, hence the most common cutaneous feature.

Among connective tissue disorders, lupus erythematosus formed the major group (65.45%) with a female predominance as depicted in [Table 2], which is similar to other studies in the literature.[1],[2],[3] Mucocutaneous manifestations of SLE are generally present in 85% of patients during the course of the disease, and musculoskeletal abnormalities are present in approximately 95%.[2] The most common cutaneous feature observed by us was photosensitivity (75%), discoid rash (41.66%), papulosquamous lesions (33.33%), and Raynaud's phenomenon (27.7%). Costner et al. have stated that photosensitivity ranges from 20% to 70%, whereas Raynaud's phenomenon has been found in 18%–46% of the patients with lupus erythematosus.[2] Kole and Ghosh showed a prevalence of discoid rash of 20% which is less than our study.[3] Nonscarring alopecia and malar rash were found in patients having features of disease activity. Zecević et al. have also recorded that these two conditions are features of disease activity.[4] One case of lupus profundus was also seen, which is a rare presentation, found in only 1%–3% of the patients as mentioned by Massone et al. and Costner et al.[2],[5]

The most common skin manifestations found in dermatomyositis patients were similar to findings by Krain, who found heliotrope rash in 67% cases, Gottron's sign in 83% cases, and periungual telangiectasias in 67% cases.[6],[7] None of the cutaneous features showed any correlation with myositis. Similar findings find a mention in the literature where the course of the skin lesions did not parallel that of the muscle disease. Only flagellate erythema, a relatively rare cutaneous finding in dermatomyositis, has been found to correlate with systemic disease activity.[6],[7]

100% of our cases of systemic sclerosis had a history of Raynaud's phenomenon and showed features of sclerodactyly and digital pitted scars, and all had mask-like facies with microstomia. 66.66% of the patients had nail fold telangiectasia and 33.33% of the patients showed salt and pepper pigmentation over extremities. Tuffanelli and Winkelmann found digital tip ulcerations in 35% of the cases.[8] Raynaud's phenomenon has been found to be associated with more than 90% cases of systemic sclerosis by Hirschl et al.[9]

Among five patients of localized scleroderma examined, two had plaque morphea, one had generalized morphea, one was with linear morphea, and one had Parry–Romberg syndrome. 40% of patients of localized morphea were of plaque type which is in concordance with Peterson et al., who found 50% cases in their study.[10]

The patient of mixed connective tissue disorder had cutaneous manifestations in the form of sclerodactyly, cutaneous ulcerations, Raynaud's phenomenon, and microstomia.[11] Only one patient had secondary Sjögren's syndrome and she had cutaneous manifestations in the form of generalized xerosis, xerostomia, and dry eyes. Since there was only one patient each of the above two diseases, comparison with other studies was not considered relevant.

All patients of psoriatic arthropathy had cutaneous involvement in the form of psoriatic plaques and 90.32% of patients had nail involvement. Nail involvement in psoriatic arthropathy was in concordance with the studies of Sobolewski et al., who found more than 80% involvement.[12] The literature review suggests that nail psoriasis is a predictor of joint disease and may occur even a few years earlier before arthritis symptoms.[12]

Predominant involvement of the scalp with psoriatic plaques was seen; however, no correlation between tender joint count and scalp involvement was found. A similar observation has been made by de Vlam et al.[13] One lady with facial lesions had severe deforming arthritis, with the onset of arthritis 5 years before the onset of cutaneous lesions. Research to date on facial psoriasis is very limited and more studies are needed; however, it is more often observed in patients with longer disease duration, family history of psoriasis, and more severe psoriasis.

Both patients of Reiter's disease had psoriasiform skin lesions, circinate balanitis, keratoderma blenorrhagicum, and severe nail involvement. Paronen found that psoriasiform skin lesions are found in nearly one-third cases of Reiter's disease, whereas keratoderma blenorrhagicum is found in only 15%–20% of cases.[14] The number of cases of Reiter's disease in this study was too less to corroborate these findings.

Among eight patients of rheumatoid arthritis evaluated, only one had rheumatoid nodules (12.5%). One lady had rheumatoid vasculitis (12.5%) which was apparently associated with poor prognosis, as she expired 3 months after developing vasculitic lesions. This finding is in concordance with the findings of Vollertsen and Conn, who stated that rheumatoid vasculitis denotes aggressive disease forms.[15],[16],[17] Extra-articular manifestations are seen, often in more aggressive forms of the disease. Other six patients had cutaneous drug-induced features such as acneiform eruptions and dermatophytosis due to oral corticosteroid intake.

The drugs exhibited to these 100 study patients included NSAIDs, methotrexate, oral corticosteroids, leflunomide, antimalarials, dapsone, TNF-alpha inhibitors, and intravenous immunoglobulin. In the 6-month follow-up, mucocutaneous side effects were observed in only patients treated with systemic corticosteroids and leflunomide. Commonly observed side effects due to oral corticosteroids included dermatophytosis (26.08%), cushingoid habitus (21.73%), acneiform eruptions (17.39%), onychomycosis (4.34%), and vulvovaginal candidiasis (4.34%), which is in accordance with the study by Saag et al.[18]

Leflunomide-induced erythema multiforme was observed in one patient of rheumatoid arthritis. A similar side effect has been observed by Fischer et al. earlier.[19] Other commonly noted adverse reactions to leflunomide include severe cutaneous adverse reactions and toxic epidermal necrolysis.[20]

The rheumatologist maybe aware of the above-mentioned numerous cutaneous findings both disease-related and drug-related, but the expertise in recognizing them and treating them at the earliest and making the rheumatologist aware of a particular finding which can modify the disease-related morbidity, the final onus lies with the dermatologist.[1],[2]


  Conclusions Top


As per available information, this unique study has hitherto been unreported in India and it highlights the association of dermatological manifestations as an important presentation of rheumatological disorders. Hence, a thorough knowledge of the dermatological manifestations of these diseases as well as collaborative clinics between the dermatologist and rheumatologist is useful for their diagnosis, management, and follow-up and for assessing prognosis.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Sontheimer RD. Skin manifestations of systemic autoimmune connective tissue disease: Diagnostics and therapeutics. Best Pract Res Clin Rheumatol 2004;18:429-62.  Back to cited text no. 1
    
2.
Costner MI, Sontheimer RD, Provost TT. Lupus erythematosus. In: Sontheimer RD, Provost TT, editors. Cutaneous Manifestations of Rheumatic Diseases. 2nd ed. Philadelphia: Lippincott Williams and Wilkins; 2004. p. 15-64.  Back to cited text no. 2
    
3.
Kole AK, Ghosh A. Cutaneous manifestations of systemic lupus erythematosus in a tertiary referral center. Indian J Dermatol 2009;54:132-6.  Back to cited text no. 3
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4.
Zecević RD, Vojvodić D, Ristić B, Pavlović MD, Stefanović D, Karadaglić D. Skin lesions – An indicator of disease activity in systemic lupus erythematosus? Lupus 2001;10:364-7.  Back to cited text no. 4
    
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Massone C, Kodama K, Salmhofer W, Abe R, Shimizu H, Parodi A, et al. Lupus erythematosus panniculitis (lupus profundus): Clinical, histopathological, and molecular analysis of nine cases. J Cutan Pathol 2005;32:396-404.  Back to cited text no. 5
    
6.
Krain L. Dermatomyositis in six patients without initial muscle involvement. Arch Dermatol 1975;111:241-5.  Back to cited text no. 6
    
7.
Callen JP. Dermatomyositis. Lancet 2000;355:53-7.  Back to cited text no. 7
    
8.
Tuffanelli DL, Winkelmann RK. Systemic scleroderma, a clinical study of 727 cases. Arch Dermatol 1961;84:359-71.  Back to cited text no. 8
    
9.
Hirschl M, Hirschl K, Lenz M, Katzenschlager R, Hutter HP, Kundi M. Transition from primary Raynaud's phenomenon to secondary Raynaud's phenomenon identified by diagnosis of an associated disease: Results of ten years of prospective surveillance. Arthritis Rheum 2006;54:1974-81.  Back to cited text no. 9
    
10.
Peterson LS, Nelson AM, Su WP, Mason T, O'Fallon WM, Gabriel SE. The epidemiology of morphea (localized scleroderma) in Olmsted county 1960-1993. J Rheumatol 1997;24:73-80.  Back to cited text no. 10
    
11.
Maddison PJ. Mixed connective tissue disease: Overlap syndromes. Baillieres Best Pract Res Clin Rheumatol 2000;14:111-24.  Back to cited text no. 11
    
12.
Sobolewski P, Walecka I, Dopytalska K. Nail involvement in psoriatic arthritis. Reumatologia 2017;55:131-5.  Back to cited text no. 12
    
13.
de Vlam K, Mallbris L, Szumski A, Jones H. Limited association between scalp psoriasis and psoriatic arthritis severity and treatment response. Clin Exp Rheumatol 2017;35:141-4.  Back to cited text no. 13
    
14.
Paronen I. Reiter's disease: A study of 344 cases observed in Finland. Acta Med Scand 1948;131:212.  Back to cited text no. 14
    
15.
Vollertsen RS, Conn DL. Vasculitis associated with rheumatoid arthritis. Rheum Dis Clin North Am 1990;16:445-61.  Back to cited text no. 15
    
16.
Magro CM, Crowson AN. The spectrum of cutaneous lesions in rheumatoid arthritis: A clinical and pathological study of 43 patients. J Cutan Pathol 2003;30:1-0.  Back to cited text no. 16
    
17.
Sayah A, English JC 3rd. Rheumatoid arthritis: A review of the cutaneous manifestations. J Am Acad Dermatol 2005;53:191-209.  Back to cited text no. 17
    
18.
Saag KG, Koehnke R, Caldwell JR, Brasington R, Burmeister LF, Zimmerman B, et al. Low dose long-term corticosteroid therapy in rheumatoid arthritis: An analysis of serious adverse events. Am J Med 1994;96:115-23.  Back to cited text no. 18
    
19.
Fischer TW, Bauer HI, Graefe T, Barta U, Elsner P. Erythema multiforme-like drug eruption with oral involvement after intake of leflunomide. Dermatology 2003;207:386-9.  Back to cited text no. 19
    
20.
Shastri V, Betkerur J, Kushalappa PA, Savita TG, Parthasarathi G. Severe cutaneous adverse drug reaction to leflunomide: A report of five cases. Indian J Dermatol Venereol Leprol 2006;72:286-9.  Back to cited text no. 20
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    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7], [Figure 8], [Figure 9]
 
 
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