Co-existence of Rheumatoid Arthritis, Vitiligo, and Bullous Pemphigoid as Multiple Autoimmune Syndrome.

Sir,

In multiple autoimmune syndromes, 3 or more autoimmune disorders evolute in a patient, manifesting their characteristic triad. Our case is a new association comprising of rheumatoid arthritis, vitiligo, and pemphigoid; all having autoimmune etiology, so far not described, hence being reported.

An 81-year-old male suffering from rheumatoid arthritis, with vitiligo over the hands, reported suffering from itchy, generalized bullous lesions for duration of 2 months. The patient also reported history of rheumatoid arthritis with deformities of duration approximately 15 years. The vitiligo skin lesions were reported to be present for the last 10 years. No family history of vitiligo and other autoimmune diseases were present. No history of offending drug intake prior to the onset of present lesion was reported.

Examination of the patient revealed multiple vesicles and tense bullous lesions over an erythematous base involving scalp, face, trunk, and extremities. Vitiligo lesions were present over the hands, legs, and trunk [Figure 1a and b]. The oral mucosa of the lip was also affected. Bulla spread sign and Nikolsky's sign were negative. Vitiligo lesions were present over the hands, legs, and trunk. Nails were deformed and dystrophic, and hair was sparse. A hematologic investigation revealed anemia with leukocytosis. Biochemical values were normal, and Tzanck test was negative. Thyroid function tests were normal; anti-thyroid antibodies were negative. Serological investigations showed elevated anti-streptolysin o titer and elevated C-reactive protein. Anti-nuclear antibodies (ANA) were negative. Radiological X-ray investigations of the skull and the chest posterior–anterior view were normal. An ultra-sonogram of the abdomen and pelvis was normal. Skin biopsy showed sub-epidermal bulla with dense dermal inflammatory infiltrate compatible with bullous pemphigoid [Figure 2]. Direct immunofluorescence could not be performed.

Figure 1

(a) Pemphigoid lesions on lower legs with deformed toes, (b) Hand deformity with vitiligo lesions

Figure 2

Sub-epidermal bulla with inflammatory infiltrate. (H and E, ×4)

Topical silver-sulfadiazine cream with antibiotic and anti-histamines were prescribed for the patient. Intravenous corticosteroid, dexamethasone was given for the pemphigoid lesions, started as 4 mg for 5 days and tapered to 2 mg from after 5 days with improvement in the bullous lesions. From the tenth day, tetracycline 2 gm./day and nicotinamide 375 mg. (tablets) twice daily were started, and corticosteroids were stopped. Topical tacrolimus was commenced for the vitiligo lesions, with good response to treatment.

Multiple autoimmune syndromes are a complex clinical entity. Three or more autoimmune disorders evolute or emerge from any one of papulosquamous, pigmentary, bullous, or collagen vascular disorder,[1] manifesting their features. However, the pathogenesis remains unclear. On analysis, it has been revealed that the presence of one autoimmune disorder may lead to the detection of other co-existing disorders like vitiligo, thyroiditis, and bullous pemphigoid[2] in the patient. Association of more number of autoimmune disorders has been documented. Humbert and Dupond classified the syndrome into 3 types[3] In addition, a new association not specified in the classification has also been reported. In this article, we report another new association of autoimmune disorder comprising rheumatoid arthritis, vitiligo, and bullous pemphigoid that has hitherto not been reported. Details of the complexity of this syndrome started emerging after community-based extensive, epidemiological, genetic, and immunological studies were undertaken in this field.[4]

Rheumatoid arthritis is an autoimmune connective tissue disorder affecting the musculoskeletal system and skin.[15] Its association with other autoimmune disorders have been reported extensively; similarly, vitiligo and its associations and bullous pemphigoid and its associations[1] have also been reported in the literature. However, the manifestations of these 3 disorders in combination and their rare association as multiple autoimmune syndromes are yet to be reported. In this article, we have reported this manifestation in an 81-year-old male patient. The treatment required a multidisciplinary management and regular follow-up. Further research and extended epidemiological, genetic, and immunological studies are essential to develop a complete understanding of this disease entity.