Abstract              Background: The concept of mixed connective tissue disease (MCTD) as a separate immune-mediated connective tissue disease (CTD) was first introduced by Gordon C. Sharp and coworkers > 40 years ago, but there is still no consensus regarding the disease definitions, the classification criteria, or the relationship with other CTDs. Aims and Objectives: To study the profile of mixed connective tissue disorders observed in the department of Medicine of a tertiary health care centre Materials and Method: In the present study all the patients with suggestive mixed connective tissue disease were selected and were tested for serum antibody in high titer (mean =1:149,200) to ribonucleoprotein. Total 28 patients were selected for the study. The demographic details including age, sex was recorded on a prestructured proforma. Presenting Features of the patients with mixed connective tissue disease was also recorded. Laboratory Findings of various laboratory test performed were also recorded. The collected data was entered in the Microsoft excel and was analyzed and presented with appropriate graphs and tables. Results: Male: female ratio was 1: 3.67. Majority of the patients were in the age group of 21-50 years of age. Majority of the patients presented with Arthritis/arthralgia (53.57%) followed by Raynaud phenomenon (17.86%) and Cutaneous lupus erythematosus (10.71%). All patients Antinuclear antibody tests was positive. The Epidermal nuclear IgG deposition was positive in 85.71% patients. Erythrocyte sedimentation rate (>30 mm per hour) was increased in 71.43%. Esophageal dysmotility occurred in 60.71% of the patients. Abnormal pulmonary function tests were present in 57.14% percent of those tested. Conclusion: Thus we conclude that mixed connective tissue disease was common in young female presenting most commonly Arthritis/arthralgia, Raynaud phenomenon and Cutaneous lupus erythematosus. On laboratory test antinuclear antibody tests, epidermal nuclear IgG deposition and raised erythrocyte sedimentation rate were common findings.

Key Words: Mixed connective tissue disease, serum antibody, Arthritis/arthralgia, Raynaud phenomenon.

 

INTRODUCTION

The concept of mixed connective tissue disease (MCTD) as a separate immune-mediated connective tissue disease (CTD) was first introduced by Gordon C. Sharp and coworkers > 40 years ago, but there is still no consensus regarding the disease definitions, the classification criteria, or the relationship with other CTDs¹. Some rheumatologists argue that MCTD is a distinct disease entity; others believe that it represents an overlap syndrome or an early and unspecific phase of an evolving, more distinct CTD; however, few studies still disregard the whole concept^2-4. As compared to the other CTDs, the research activity on MCTD has been relatively low from the late 1990s. Unfortunately, as a result, a large proportion of the standard textbook references on MCTD include >20 years old and originate from relatively small and potentially skewed single-center hospital cohorts^5-8. An extensive study of MCTD has not been conducted recently due to the following four interrelated reasons: 1) the controversies regarding the concept may have dampened the enthusiasm of some researchers; 2) the apparent rarity of the disease, with a concomitant lack of population based epidemiology estimates, has made it difficult to plan and design MCTD studies; 3) the lack of clear disease definitions has made it difficult to delineate MCTD from the other CTDs; and 4) the lack of internationally accepted consensus criteria for disease classification has reduced the possibility of comparative studies.

 

MATERIALS AND METHOD

The present study was conducted in the department of medicine of Dr. Ulhas Patil Medical College and Hospital The study was conducted from January 2015 to December 2016. All the patients with suggestive mixed connective tissue disease were selected and were tested for serum antibody in high titer (mean =1:149,200) to ribonucleoprotein. Thus total 28 patients were selected for the study. The demographic details including age, sex was recorded on a prestructured proforma. Presenting Features of the patients with mixed connective tissue disease was also recorded. Laboratory Findings of various laboratory test performed were also recorded. Antibody to extractable nuclear antigen was determined by the hemagglutination method of Sharp and co-workers.⁹ This test was carried out using ENA-coated sheep erythrocytes before and after ribonuclease (RNase) treatment. A fall in titer of four or more dilutions after treatment was interpreted as ribonuclease-sensitive and indicative of antibody to ribonucleoprotein. Cutaneous immunoglobulin deposits were detected by direct immunofluorescence of biopsy specimens of both normal skin exposed to the sun (wrist and forearm) and nonexposed skin (medial forearm near the antecubital fossa, back or buttock) as previously described.¹⁰ The antinuclear antibody (ANA) test was carried out by the method of Holborow and colleagues¹¹; total hemolytic complement (CH50) by the method of Kabat and Mayer¹²; the third and fourth components of complement (C3 and C4) were measured by radial immunodiffusion; the Clq component of complement was determined by the method of Agnello and associates.¹³ Antibody to double-stranded (native) DNA was determined by the millipore filter assay of Ginsberg and Keiser.¹⁴ Ninety-five percent confidence intervals are recorded for each clinical or laboratory observation. The collected data was entered in the Microsoft excel and was analyzed and presented with appropriate graphs and tables.

 

RESULTS

Table 1: Distribution of patients according to age and sex

Variable		No. of Cases	Percentage
Sex	Male	6	21.43
	Female	22	78.57
Age group	≤20	1	3.57
	21-30	5	17.86
	31-40	9	32.14
	41-50	7	25.00
	51-60	4	14.29
	>60	2	7.14

It was seen that majority of the patients suffering from mixed connective tissue disorders were female (78.57%) with 1: 3.67 of male: female ratio. It was observed that majority of the patients were in the age group of 21-50 years of age. 

 

Table 2: Presenting Features in Patients with Mixed Connective Tissue Disease

Majority of the patients presented with Arthritis/arthralgia (53.57%) followed by Raynaud phenomenon (17.86%) and Cutaneous lupus erythematosus (10.71%).

Table 3: Distribution according to Laboratory Findings

It was seen that in all patients Antinuclear antibody tests was positive. The Epidermal nuclear IgG deposition was positive in 85.71% patients. Erythrocyte sedimentation rate (>30 mm per hour) was increased in 71.43%.  Esophageal dysmotility occurred in 60.71% of the patients. Abnormal pulmonary function tests were present in 57.14% percent of those tested.

 

DISCUSSION

The present study was conducted to study the patients of mixed connective tissue disease observed in department of medicine. It was seen that majority of the patients suffering from mixed connective tissue disorders were female (78.57%) with 1: 3.67 of male: female ratio. It was observed that majority of the patients were in the age group of 21-50 years of age.  In the study done by Stephen D. Prystowsky¹⁵ 39 patients were women and 7 were men (sex ratio, 5.6:1) and ages ranged from 9 to 53 years, with a mean age of 36. MCTD is now recognized to occur throughout the world. It is predominantly a disease of females, with female to male ratio of 16:1.¹⁶ The disease is seen among all age groups range from 4 – 80 years; the mean age of onset in adult is 35 years and 10 years in children. The incidence was low when compared with other collagen disease like systemic lupus erythematosus, dermatomyositis/polymyositis, rheumatoid arthritis and Scleroderma. Majority of the patiens presented with Arthritis/arthralgia (53.57%) followed by Raynaud phenomenon (17.86%) and Cutaneous lupus erythematosus (10.71%). Similar findings were also observed by Stephen D. Prystowsky ¹⁵. The diagnosis of MCTD should be suspected in patients with Raynaud phenomenon and nondeforming (nonerosive) arthritis or arthralgia. Such cases are sometimes misdiagnosed as rheumatoid arthritis because these patients frequently have high-titered rheumatoid factors (RF). It appears that moderate to severe erosive arthritis is uncommon in patients with anti-RNP even in the presence of prolonged elevations of RF. The combination of subacute or chronic cutaneous lupus erythematosus, Raynaud phenomenon and arthralgia is frequently observed by dermatologists and appears to have a high association with anti-RNP. We recently observed the high prevalence of subacute and chronic coetaneous LE in this RNP subset.¹⁷ In the present study we observed that in all patients Antinuclear antibody tests was positive. The Epidermal nuclear IgG deposition was positive in 85.71% patients. Erythrocyte sedimentation rate (>30 mm per hour) was increased in 71.43%. Esophageal dysmotility occurred in 60.71% of the patients. Abnormal pulmonary function tests were present in 57.14% percent of those tested. The laboratory manifestation includes Anemia, leucopenia, elevated erythrocyte sedimentation rate, hypergammaglobulinemia (100%), positive coombs test, and Rheumatoid factor positive in 50 to 70% of patients. Antinuclear antibody positivity is seen in 100% of patients in high titre with coarse speckled pattern. Anti U1RNP antibodies by haemagglutination test is highly characteristic feature of MCTD. Many patients also make antibodies directed against hnRNP-A2, fibrillin-1, and nucleosomes, but not to RNA polymerases¹⁸. The absence of anti-Sm antibodies and anti-DNA antibodies in a sero positive for anti U1RNP is an important discriminating finding for MCTD from SLE. Antiphospholipid antibodies occur, but are less common than in those with SLE.¹⁹

 

CONCLUSION

Thus we conclude that mixed connective tissue disease was common in young female presenting most commonly Arthritis/arthralgia, Raynaud phenomenon and Cutaneous lupus erythematosus. On laboratory test antinuclear antibody tests, epidermal nuclear IgG deposition and raised erythrocyte sedimentation rate were common findings.

 

REFERENCES

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