Introduction

Multiple autoimmune syndrome is defined by the coexistence of at least three different autoimmune diseases which can occur simultaneously or over several years of evolution. We report an exceptional association of vitiligo, autoimmune thrombocytopenia and autoimmune dermoepidermal bullous dermatosis.

Observation

A young patient of 35 years presented since the age of 14 achromic non-painful or pruritic lesions which gradually extended to the level of the body. 4 years ago he developed intermittent oral and nasal erosions associated with red eyes and a decrease of visual acuity impeding his daily and professional activities. He also reported episodic appearance of some liquidiennes skin lesions without signs of infection or systemic disease.

Ocular examination revealed bilateral red eyes with Symblepharon, and corneal dystrophy (Figure 1). Cutaneous examination revealed at the left leg the presence of tense bullae with clear contents based on healthy skin, associated with hemorrhagic erosions (Figure 2). The Nikolsky's sign was negative. There were also extensive achromic patches (Figure 3).

1. 

   Figure Options

   • View in workspace

   Figure 1:

   Symblepharon of the left eye.
   
   
   

1. 

   Figure Options

   • View in workspace

   Figure 2:

   Erosions with tense bullae of the left leg.
   
   
   

1. 

   Figure Options

   • View in workspace

   Figure 3:

   Achromic patches of inferior members.
   
   
   

Laboratory test showed thrombocytopenia at 32000 / mm3. We completed the investigation by sternal puncture which showed a hypercellular marrow with megakaryocytic hyperplasia in support of a peripheral autoimmune origin. Thyroid and anti-nuclear antibody were negative. Conjunctively biopsy made by ophthalmologists initially objectified the presence of functional cleavage and direct immunofluorescence showed immunoglobulin G and complement C3 deposition in a linear band at the dermal-epidermal junction. The immune microscopy was not performed because this technique is not available in our hospital.

According to the clinical context and the results of immune histology we retained in our patient the combination of three autoimmune diseases: vitiligo, autoimmune thrombocytopenia with autoimmune bullous derma epidermal dermatitis most probably cicatricle pemphigoid. Epidermolysis bullosa acquisita that looks like cicatricle pemphigoid cannot be ruled out given the lack of examination by immune-microscopy.

The patient was initially put on oral corticosteroids at a dose of 1mg / kg / day until normalization of platelet levels. Then treatment with daps one at a dose of 2 mg / kg / day associated with mycofenolate mofetil at a rate of 2g / day was initiated with a clinical and laboratory monitoring. The evolution was marked by the stabilization of the disease and a slight improvement in ocular involvement.

Disscussion

We report a unique case characterized by the association of vitiligo, an autoimmune thrombocytopenia and autoimmune dermo epidermal bullous dermatosis in a male patient. It is still uncommon because different studies showed female predominance associations of auto-immune diseases [11. Humbert P, Dupond JL (1988) Multiple autoimmune syndromes. Ann Med Interne 139: 159-168.].

Multiple autoimmune syndrome is a condition in which patients have at least three distinct autoimmune diseases [11. Humbert P, Dupond JL (1988) Multiple autoimmune syndromes. Ann Med Interne 139: 159-168.], often with at least one dermatological condition, usually vitiligo or alopecia areata. Indeed in many cases of multiple autoimmune syndromes reported in the medical literature, vitiligo is the first autoimmune disease to be diagnosed. In these cases, the vitiligo is usually bilateral and symmetrical, which is illustrated by our observation. Autoimmune thyroid disease was also present in the multiple autoimmune syndrome including vitiligo [11. Humbert P, Dupond JL (1988) Multiple autoimmune syndromes. Ann Med Interne 139: 159-168.]. It is not the case of our patient or may be not yet. In a predisposed person real cascade of autoimmune diseases may extend over several years (17 years in our case) and must therefore be watched to intervene on time. Other combinations are possible so we asked routinely laboratory tests to look for other most frequent associations which are anemia, diabetes, and systemic lupus. Other autoimmune related diseases are described in the literature as alopecia, inflammatory colitis, Myasthenia, Sjogren's syndrome, scleroderma, rheumatoid arthritis, psoriasis and pemphigus [22. Jacobson DL, Gange SJ, Rose NR, Graham NM (1997) Epidemiology and estimated population burden of selected autoimmune diseases in the United States. Clin Immunol Immunopath 84: 223 – 243.,33. Loftus EV, Sandborn WJ (2002) Epidemiology of inflammatory bowel disease. Gastroenterol Clin N Am 31: 1 – 20.].

For autoimmune thrombocytopenia, its association with autoimmune derma epidermal bullous dermatitis has been reported in patients with bullous pemphigoid but has never been described with a cicatricle pemphigoid [44. Gayle Taylor, Vanessa Venning, Fenella Wojnarowska (1993) Bullous pemphigoid and associated autoimmune thrombocytopenia: Two case reports. J Am Acad Dermatol 29: 900–902.] or epidermolysis bullosa acquisita.

The presence of auto-immune disorders associated with cicatricial pemphigoid is increased compared to the risk of the general population. A study on a group of 34 patients with cicatricial pemphigoid showed that thirty-two percent of patients had autoimmune disease against 7% in the control population (p less than 0.002) [55. Nayar M, Wojnarowska F, Venning V, Taylor CJ (1991): Association of autoimmunity and cicatricial pemphigoid: is there an immunogenetic basis? J Am Acad Dermatol 25: 1011–1015. ,66. Foster CS (1986) Cicatriciel pemphigoid. Trans Am Ophtalmol Soc 139: 159-168. ]. Another study by Foster on a series of 130 patients followed for cicatricial pemphigoid noted the presence of autoimmune diseases associated in 17.7%, which is significantly higher compared to the 4% risk observed in the general population [55. Nayar M, Wojnarowska F, Venning V, Taylor CJ (1991): Association of autoimmunity and cicatricial pemphigoid: is there an immunogenetic basis? J Am Acad Dermatol 25: 1011–1015. ]. Associations reported in this context are lupus [77. Redman RS, Thorne EG (1981) Cicatricial Pemphigoid in a Patient with Systemic Lupus Erythematosus. Arch dermatol 117: 109-110. ], rheumatoid arthritis [88. Spigel GT, Winkelmann RK (1978) Cicatricial pemphigoid and rheumatoid arthritis. Arch Dermatol 114: 415-417.], or mixed connectivitis [99. Veien NK (2010): Bullous pemphigoid masquerading as recurrent vesicular hand eczema. Acta Derm Venereol 90: 4–5.,1010. Malik M, Gürcan HM & Ahmed AR (2010): Coexistence of mucous membrane pemphigoid and connective-tissue disease. Clin Exp Dermatol 35: 156–159. ].

For the epidermolysis bullosa acquisita, it has been reported in association especially with inflammatory colitis [1111. Hundorfean G, Neurath MF, Sitaru C (2010) Autoimmunity against type VII collagen in inflammatory bowel disease. J Cell Mol Med 14: 2393-2403. ] with a few cases of association with multiple myeloma [1212. Engineer L, Dow EC, Braverman IM (2002) Epidermolysis bullosa acquisita and multiple myeloma. J Am Acad Dermatol 47: 943-946.], psoriasis, rheumatoid arthritis, Hashimoto's thyroiditis and diabetes [1313. Endo Y, Tamura A, Ishikawa O (1997) Psoriasis vulgaris coexistent with epidermolysis bullosa acquisita. Br J Dermatol 137: 783-786.].

Autoimmune diseases involve genetic and environmental factors [1414. Gardner KM, Rajacich M (1985) Ophtalmological manifestations of adult rheumatoid arthritis and cicatriciel pemphigoid. Int Ophtalmol clin 25: 1-35.]. Concerning the genetic factor, the clinical observation of familial cases suggests that there are genes that predispose to such diseases, on the other hand once triggered the autoimmune disease amplifies via a cellular destruction mechanism that induce release of new auto antigens that were previously protected by a cytoplasmic or nuclear membrane, and have not been in contact with cells of the immune system. The immune system will then elicit immune responses against these «unknown» auto antigens [1515. Bonnott B (2004) Physiopathologie des maldies auto-immunes. Rev Med Interne 25: 648-658.,1616. Vanderlugt CI, Neville KL, Nikcevich KM, Eagar TN, Bluestone JA, et al. (2000) Pathologic role and temporal appearance and newly emerging autoepitopes in relapsing experimental autoimmune encephalo-myelitis. J Immunol 164: 670-678.].

Conclusion

The presence of autoimmune disease increases the risk of developing other autoimmune diseases indicating the need of monitoring of these patients.