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CASE REPORT
Year : 2020  |  Volume : 21  |  Issue : 2  |  Page : 153-155

Blau syndrome: A case report of a rare granulomatous disorder


Department of Dermatology, Armed Forces Medical College, Pune, Maharashtra, India

Date of Submission04-Mar-2019
Date of Decision24-Mar-2019
Date of Acceptance10-Feb-2020
Date of Web Publication01-Apr-2020

Correspondence Address:
Preema Sinha
Department of Dermatology, Armed Forces Medical College, Pune - 411 040, Maharastra
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijpd.IJPD_23_19

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  Abstract 


Blau syndrome is a rare condition characterized by the triad of granulomatous skin lesions, symmetric polyarthritis with boggy joint swellings, and ocular inflammation. It has an autosomal dominant mode of inheritance and occurs due to a mutation in CARD-15/NOD-2 gene which encodes the cytosolic NOD2 protein, a key molecule in the regulation of innate immunity. Clinical onset is generally in the 1st year of life and is characterized by articular, cutaneous, and ocular noncaseating granulomatous inflammation, which can be variably associated with a heterogeneous systemic spectrum. Here, we describe one such rare case.

Keywords: Blau syndrome, granulomatous dermatitis, polyarthritis, uveitis


How to cite this article:
Sinha P, Kartik S, Bhatia JK, Choden T. Blau syndrome: A case report of a rare granulomatous disorder. Indian J Paediatr Dermatol 2020;21:153-5

How to cite this URL:
Sinha P, Kartik S, Bhatia JK, Choden T. Blau syndrome: A case report of a rare granulomatous disorder. Indian J Paediatr Dermatol [serial online] 2020 [cited 2020 May 26];21:153-5. Available from: http://www.ijpd.in/text.asp?2020/21/2/153/281734




  Introduction Top


Blau syndrome is a rare granulomatous autoinflammatory syndrome, first described by an American pediatrician Blau in the year 1985 as a dominantly inherited disorder.[1],[2] Miceli-Richard et al. identified the responsible gene, the caspase recruitment gene: NOD2, mapped to chromosomal region 16q12.1–13 in 2001.[3] It is an integral part of the innate immunity and is expressed in macrophages, dendritic cells, and epithelial cells.

Blau syndrome classically presents in early childhood as a triad of granulomatous dermatitis, arthritis, and uveitis. Although there are exceptions, skin rash is the first symptom to appear, usually in the 1st year of life. Between the ages of 2–4 years, a boggy polyarthritis is observed. Finally, uveitis develops in 60%–80% of patients at around 48 months of age.[4]

We report this rare syndrome in a female who presented to our outpatient department (OPD) with the classical triad of recurrent uveitis, arthritis, and dermatitis but with the onset of skin lesions after arthritis.


  Case Report Top


A 14-year-old girl presented to the dermatology OPD with complaints of recurrent painless swelling of multiple joints of the body for last 12 years, with a history of multiple exacerbations and remissions and history of multiple skin-colored, nonitchy, pinhead-sized eruptions over the body for the past 10 years. She also gave a history of blurring of vision with recurrent episodes of redness and watering of eyes and photophobia for the past 10 years. The patient presented to our hospital with an exacerbation of her symptoms in the form of painless swelling in the ankle and wrist joints and persistent nonitchy skin-colored eruptions over the body. Till date, she was being managed as a case of juvenile rheumatoid arthritis with atopic dermatitis.

General and systemic examination was within the normal limits. Examination of the musculoskeletal system revealed diffuse boggy swelling of the ankle and wrist joints with no overlying feature suggestive of inflammation in the form of pain, redness, or restriction of movement [Figure 1]a and [Figure 1]b. Dermatological examination revealed multiple discrete skin-colored papules distributed diffusely over the trunk and both upper and lower extremities [Figure 2]a and [Figure 2]b.
Figure 1: (a) Wrist joints showing boggy polyarthritis. (b) Ankle joints showing boggy polyarthritis

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Figure 2: (a) Multiple discrete skin-colored papules seen over the forearm. (b) Multiple discrete skin-colored papules over the chest and abdomen

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Investigations revealed an elevated erythrocyte sedimentation rate (ESR) of 60 mm fall at the end of the 1st h and positive C-reactive protein with a negative rheumatoid factor. Other hematological and biochemical parameters were within the normal limits. Antinuclear antibodies by indirect immunofluorescence were negative. Ultrasound of the wrist joints showed tendinitis over both the wrists. In view of persistent symptoms of joint swelling, left wrist arthroscopy and synovial biopsy were done under general anesthesia. Intraoperative findings included enlarged synovium with a thick synovial membrane.

Synovial biopsy revealed multiple noncaseating epithelioid granulomas with Langhans-type multinucleate giant cells with a mixed inflammatory infiltrate of lymphocytes, histiocytes, and plasma cells suggestive of granulomatous synovitis [Figure 3]a and b]. A skin biopsy performed from the papular lesions on the trunk revealed discrete epithelioid cell granulomas in the dermis without caseation necrosis consistent with sarcoidosis [Figure 4]a and [Figure 4]b.
Figure 3: (a) Synovial biopsy shows noncaseating epithelioid granulomas with Langhans-type multinucleate giant cells with a mixed inflammatory infiltrate (H and E × 100). (b) High-power view of synovial biopsy showing noncaseating granulomas and mixed inflammatory infiltrate of lymphocytes, histiocytes, and plasma cells (H and E ×400)

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Figure 4: (a) Skin biopsy shows epithelioid cell granulomas in the dermis without caseation necrosis (H and E ×100). (b) High-power view of skin biopsy shows epithelioid cell granulomas in the dermis without caseation necrosis (H and E Stain ×400)

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In view of granulomatous polyarthritis, granulomatous dermatitis suggestive of sarcoidosis and a history of recurrent uveitis, a diagnosis of Blau syndrome comprising the above triad was made. The patient was started on oral methotrexate to which she was responding well with the reduction in arthritis as well as the resolution of skin lesions.


  Discussion Top


Blau syndrome is the only autoinflammatory disease associated with a gain of function mutation to show granulomatous inflammation. Individuals with Blau syndrome generally present in early childhood with articular, skin, and ocular involvement. Blau arthritis the most common presentation, typically presents as a unique phenotype “boggy or exuberant synovitis,” appearing in the first decade of life involving peripheral joints such as the wrists, knees, ankles, and proximal interphalangeal joints commonly.[5] Tenosynovitis is also a common presentation for many patients. However, despite the chronic exuberant arthritis, joint destruction is hardly encountered.

Skin manifestation usually begins as a fine mildly scaly maculomicropapular erythematous rash, which evolves into multiple papules, later on becoming confluent.[6] Appearance is often symmetric on the extremities and trunk. The rash may sometimes have a dirty scaly appearance. The rash is generally the first presentation; however, in our patient, arthritis preceded the skin lesions by 2 years. These patients are often treated as atopic dermatitis.

Ocular involvement of Blau syndrome is associated with significant morbidity seen in nearly 80% of patients. It is characterized by ocular pain, blurry vision, photophobia, and predominantly posterior uveitis. It can evolve into panuveitis, with multifocal choroiditis, but involvement is usually bilateral.[5],[6] Our patient gave a history of blurring of vision with recurrent episodes of redness and watering of eyes in the past.

Extra-triad and atypical manifestations are described with liver, renal, vascular, and pulmonary involvement which include fever, sialadenitis, hypertension, pericarditis, transient neuropathies, pulmonary embolism, hepatic and splenic involvement, large-vessel vasculitis, chronic renal failure, and erythema nodosum.[6],[7],[8],[9]

Erythema nodosum is the second most common cutaneous manifestation followed by leukocytoclastic vasculitis. Recalcitrant large leg ulcers showing granulomas on histopathology have also been described in some patients.[5]

Pathological analysis of involved tissues shows nonnecrotizing and noncaseating granulomas of the biopsied tissue. Laboratory analysis may show normal to markedly elevated inflammatory markers, including ESR and C-reactive protein.

As a result of varied clinical manifestations and rarity of the condition, there is no optimal treatment for Blau syndrome. To date, the treatments consist of nonsteroid anti-inflammatory drugs, corticosteroids, and thalidomide, and in refractory cases, treatments consist of immunosuppressive agents, such as methotrexate, colchicine, azathioprine, and mycophenolate mofetil. Recently, biologic agents such as interleukin-1 blockers and tumor necrosis factor-α inhibitors have represented promising therapeutic approaches in cases of an unsatisfactory response.[5],[6],[10]

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.
Punzi L, Gava A, Galozzi P, Sfriso P. Blau syndrome. Best Pract Res Clin Rheumatol 2011;25:703-14.  Back to cited text no. 1
    
2.
Blau EB. Familial granulomatous arthritis, iritis, and rash. J Pediatr 1985;107:689-93.  Back to cited text no. 2
    
3.
Miceli-Richard C, Lesage S, Rybojad M, Prieur AM, Manouvrier-Hanu S, Häfner R, et al. CARD15 mutations in Blau syndrome. Nat Genet 2001;29:19.  Back to cited text no. 3
    
4.
Borzutzky A, Fried A, Chou J, Bonilla FA, Kim S, Dedeoglu F. NOD2-associated diseases: Bridging innate immunity and autoinflammation. Clin Immunol 2010;134:251-61.  Back to cited text no. 4
    
5.
Wouters CH, Maes A, Foley KP, Bertin J, Rose CD. Blau syndrome, the prototypic auto-inflammatory granulomatous disease. Pediatr Rheumatol Online J 2014;12:33.  Back to cited text no. 5
    
6.
Rose CD, Martin TM, Wouters CH. Blau syndrome revisited. Curr Opin Rheumatol 2011;23:411-8.  Back to cited text no. 6
    
7.
Sfriso P, Caso F, Tognon S, Galozzi P, Gava A, Punzi L. Blau syndrome, clinical and genetic aspects. Autoimmun Rev 2012;12:44-51.  Back to cited text no. 7
    
8.
Saini SK, Rose CD. Liver involvement in familial granulomatous arthritis (Blau syndrome). J Rheumatol 1996;23:396-9.  Back to cited text no. 8
    
9.
Becker ML, Martin TM, Doyle TM, Rosé CD. Interstitial pneumonitis in Blau syndrome with documented mutation in CARD15. Arthritis Rheum 2007;56:1292-4.  Back to cited text no. 9
    
10.
Gattorno M, Federici S, Pelagatti MA, Caorsi R, Brisca G, Malattia C, et al. Diagnosis and management of autoinflammatory diseases in childhood. J Clin Immunol 2008;28 Suppl 1:S73-83.  Back to cited text no. 10
    


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4]



 

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