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Table of Contents
Year : 2020  |  Volume : 9  |  Issue : 2  |  Page : 120-123

An unusual case of dominant dystrophic epidermolysis bullosa (Cockayne-Touraine disease) associated with juvenile idiopathic arthritis

1 Department of Medicine, Sri Venkateswara Institute of Medical Sciences, Tirupati, Andhra Pradesh, India
2 National Health Private Limited, JP Nagar, Bengaluru, Karnataka, India
3 Department of Pathology, Sri Venkateswara Institute of Medical Sciences, Tirupati, Andhra Pradesh, India

Date of Submission23-Jun-2018
Date of Decision27-Jun-2019
Date of Acceptance27-Jun-2019
Date of Web Publication4-Aug-2020

Correspondence Address:
K M Bhargav
Assistant Professor, Department of Medicine, Sri Venkateswara Institute of Medical Sciences, Tirupati 517 507, Andhra Pradesh
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/JCSR.JCSR_14_20

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We report a rare case of co-existence of dominant dystrophic epidermolysis bullosa (EB) and juvenile idiopathic arthritis (JIA) in an 18-year-old male patient, who is born out of consanguineous marriage. He presented with blistering skin lesions all over the body since the 2nd day after his birth, anonychia of all the toes from childhood and symmetric polyarticular inflammatory arthritis for 4 years. Erythrocyte sedimentation rate and C-reactive protein were elevated. Skin biopsy of induced vesicle was done, and histopathology showed epidermis with basket-weave hyperkeratosis, basal pigmented layer and sub-epidermal free bulla, while dermis revealed a few thin-walled proliferating capillaries with sparse lymphocytes surrounding them. Immunofluorescence showed immunoglobulin G along the basement membrane confirming the diagnosis of EB. He was diagnosed to have polyarticular rheumatoid factor-negative JIA. Treatment with oral methylprednisolone, disease-modifying anti-rheumatic drugs and intra-articular triamcinolone injections resulted in symptomatic relief of the joint pains.

Keywords: Epidermolysis bullosa, dominant dystrophic, juvenile idiopathic arthritis

How to cite this article:
Raja V A, Bhargav K M, Reddy P S, Neeharika T, Suryudu R, Bhattaram S, Kumar B S, Rukmangadha N. An unusual case of dominant dystrophic epidermolysis bullosa (Cockayne-Touraine disease) associated with juvenile idiopathic arthritis. J Clin Sci Res 2020;9:120-3

How to cite this URL:
Raja V A, Bhargav K M, Reddy P S, Neeharika T, Suryudu R, Bhattaram S, Kumar B S, Rukmangadha N. An unusual case of dominant dystrophic epidermolysis bullosa (Cockayne-Touraine disease) associated with juvenile idiopathic arthritis. J Clin Sci Res [serial online] 2020 [cited 2020 Oct 31];9:120-3. Available from: https://www.jcsr.co.in/text.asp?2020/9/2/120/291367

  Introduction Top

Epidermolysis bullosa (EB) is a rare inherited connective tissue disorder that comprises a collection of blistering diseases that affect the skin, mucous membranes or rarely other organs.[1] EB is divided into three main categories (simplex, junctional and dystrophic) based on the level of tissue separation within the basement membrane zone.[2] Dystrophic EB is due to the mutations in the COL7A1 gene encoding type VII collagen.[3] Dystrophic EB is divided into three types based on the pattern of inheritance: dominant dystrophic EB (DDEB), recessive dystrophic EB and severe generalised recessive dystrophic EB.[2]

Juvenile idiopathic arthritis (JIA) is an autoimmune inflammatory joint disease that is associated with significant disability to the patient. It is the most common cause of arthritis in children and adolescents. The aetiopathogenesis of JIA is similar to rheumatoid arthritis but with less cartilage erosion, less joint instability and absent rheumatoid factor (RF). The pooled data from various reports showed that there was wide variation in incidence rates of JIA from 16 to 230 per million in European population.[4] We report here a rare case of co-existence of DDEB with JIA.

  Case Report Top

An 18-year-old male patient came to the medicine outpatient department with complaints of blistering of skin all over the body. It started as blistering of skin of hands and feet on the 2nd day after birth. Gradually, he had blistering of skin all over the body either on trivial trauma or spontaneously. The blisters healed with hyperpigmentation and scarring. He also had complaints of multiple joint pains of 3 years' duration, which were symmetrical in distribution and were associated with morning stiffness and swelling of the joints. He had limitation in the daily physical activities due to joint pains. He was born out of consanguineous marriage and his elder sibling had severe mental retardation.

On examination, a number of vesicles and bullae of various sizes were seen all over the body ([Figure 1]); many hyperpigmented macules, erosions, bullae and scars were present, suggestive of healed blisters ([Figure 1]a and c). Nikolsky's sign was positive. Teeth were disarranged, especially in the lower jaw as shown in [Figure 1]b. He had anonychia in all the toes ([Figure 1]d). He had swollen bilateral knee and ankle joints with effusion ([Figure 1]e). Oral mucosa showed no erosions. Scalp and body hair were normal. Vital signs were within normal limits and systemic examination was unremarkable.
Figure 1: Clinical photograph showing hyperpigmented macules over the skin suggestive of healed blisters (a), disarranged teeth of lower jaw (b), bullae and erosions over the dorsum of hand (c), anonychia of all toes (d) and gross swelling of the left knee joint due to effusion (e)

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An initial presumptive clinical diagnosis of EB with inflammatory arthritis was made, and the patient was admitted to the ward for further evaluation. He had elevated total leucocyte count, erythrocyte sedimentation rate and C-reactive protein. RF was negative. Antinuclear antibody profile and anti-cyclic citrullinated peptide (anti-CCP) tested negative.

A vesicle was induced on the forearm and skin biopsy was done at that site. Histopathological examination and immunofluorescence of the biopsy specimen revealed epidermis with basket-weave hyperkeratosis, basal pigmented layer and sub-epidermal cell free bulla. Dermis revealed cutaneous adnexal structures and a few thin-walled proliferating capillaries with sparse lymphocytes around them ([Figure 2]). Immunofluorescence showed immunoglobulin G along the basement membrane; immunoglobulin A, immunoglobulin M and C3 tested were negative. The histopathology and immunofluorescence confirmed the diagnosis of EB. The patient was diagnosed to have polyarticular RF-negative JIA with DDEB.[1]
Figure 2: Skin biopsy. Photomicrograph showing hyperkeratosis and sub-epidermal bulla (Haematoxylin and eosin, ×100) (a). Photomicrograph showing 'basket-weave' hyperkeratosis (Haematoxylin and eosin, ×200) (b)

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The patient was treated with oral methylprednisolone, disease-modifying anti-rheumatic drugs (DMARDs) and intra-articular triamcinolone injections; the joint pains have subsided with the treatment. The patient was discharged after counselling and educating him and his attenders about the nature of the disease, the benefits and harms of drugs, the importance of skin and oral hygiene, the need for regular hospital visits and the harms of consanguineous marriage in their family.

  Discussion Top

This case is an infrequent combination of two autoimmune disorders, EB and JIA. The present patient has inherited autosomal dominant EB with sporadically occurring JIA. Blistering skin diseases may be broadly classified into three, namely genetic blistering diseases, immunobullous disorders and others.[2] EB falls into the genetic blistering disease of the skin category. The EB is again subdivided into four main types based on the site of the split of the skin. They are simplex, junctional, dystrophic and kindler variety affecting the epidermis, junction and dermis layers, respectively. According to a US registry, incidence (/million) and prevalence (/million) of EB have been estimated to be 19 and 8 respectively;[5] the incidence (/million) and prevalence (/million) of DDEB has been estimated to be 2.86 and 0.99 respectively.[5] Indian data are not clearly known.

Earlier on the dominant variant was called by two different names, 'Cockayne-Touraine syndrome' and 'Pasini disease'.[2] The clinical manifestation of DDEB is subtle, with blisters restricted to peripheries extremities which heal with scarring; milia, nail changes and dental caries may also be evident. The diagnosis is ascertained by electron microscopy and immunofluorescence staining of the skin biopsy. The disease can be confirmed and further sub-classified by the use of molecular diagnostic tests. In our patient, diagnosis established by DDEB is mainly managed symptomatically and by the prevention of infections. As it is a genetically transmitted disease, it can be prevented in the offspring, by offering proper counselling to the couples suffering from existing disease. DDEB has an excellent prognosis in comparison to recessive variants as the propensity for malignancies is less.

A cluster of chronic inflammatory arthritis disorders affecting children under age of 16 years is categorised as JIA. The JIA is majorly divided into seven types, namely systemic JIA, oligoarticular JIA, RF-positive polyarticular JIA, RF-negative polyarticular JIA, psoriatic JIA, enthesitis-related JIA and undifferentiated arthritis.[6] The causative factor for the triggering and progression of the disease is unknown. It is thought that both the environmental agents and genes play a role. HLA genes, other inflammatory mediator genes and infectious agents are involved in the disease pathogenesis.[7] Most cases are sporadic. The diagnosis of JIA is difficult and is mostly clinical. The disease is treated with non-steroidal anti-inflammatory drugs earlier; later, DMARDs secured their place; and now, the recently surfaced biologics are used.[8] Formerly, it was treated aggressively at the onset of the disease; now, the paradigm is shifted to slow add-on therapy approach.

In this instance, we discuss a unique case of DDEB associated with JIA. The dominant form is usually mild and is not associated with any systemic problems, while the recessive form is severe and is familiar to have associations with connective tissue diseases. This case represents a very good example to say that immune system is triggered by antigens in the skin and can lead to various autoimmune conditions. It is prudent to evaluate other systemic manifestations even with DDEB.

In EB, other autoimmune and inflammatory disorders may co-exist; hence, thorough evaluation must be carried out. The occurrence of new mutant collagen and the exposure of new antigens to the immune system due to the separation of epidermis and dermis can trigger autoimmune conditions in patients with EB. Early diagnosis and treatment of autoimmune conditions can prevent disability.

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Conflicts of interest

There are no conflicts of interest.

  References Top

Petty RE, Southwood TR, Manners P, Baum J, Glass DN, Goldenberg J, et al. International League of Associations for Rheumatology classification of juvenile idiopathic arthritis: Second Revision, Edmonton, 2001. J Rheumatol 2004;31:390-2.  Back to cited text no. 1
Fine JD, Bruckner-Tuderman L, Eady RA, Bauer EA, Bauer JW, Has C, et al. Inherited epidermolysis bullosa: Updated recommendations on diagnosis and classification. J Am Acad Dermatol 2014;70:1103-26.  Back to cited text no. 2
Dang N, Murrell DF. Mutation analysis and characterization of COL7A1 mutations in dystrophic epidermolysis bullosa. Exp Dermatol 2008;17:553-68.  Back to cited text no. 3
Thierry S, Fautrel B, Lemelle I, Guillemin F. Prevalence and incidence of juvenile idiopathic arthritis: A systematic review. Joint Bone Spine 2014;81:112-7.  Back to cited text no. 4
Pfendner E, Uitto J, Fine JD. Epidermolysis bullosa carrier frequencies in the US population. J Invest Dermatol 2001;116:483-4.  Back to cited text no. 5
Petty RE, Southwood TR, Baum J, Bhettay E, Glass DN, Manners P, et al. Revision of the proposed classification criteria for juvenile idiopathic arthritis: Durban, 1997. J Rheumatol 1998;25:1991-4.  Back to cited text no. 6
Murray K, Thompson SD, Glass DN. Pathogenesis of juvenile chronic arthritis: Genetic and environmental factors. Arch Dis Child 1997;77:530-4.  Back to cited text no. 7
Harris JG, Kessler EA, Verbsky JW. Update on the treatment of juvenile idiopathic arthritis. Curr Allergy Asthma Rep 2013;13:337-46.  Back to cited text no. 8


  [Figure 1], [Figure 2]


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