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A patient with Pfeifer-Weber-Christian Disease - Successful Therapy with Cyclosporin A: case report
© Pongratz et al; licensee BioMed Central Ltd. 2010
Received: 20 August 2009
Accepted: 27 January 2010
Published: 27 January 2010
Pfeifer-Weber-Christian disease (PWCD) is a rare inflammatory disorder of the subcutaneous fatty tissue. The diagnosis and therapy of this rare type of panniculitis is still controversial and will be discussed in this article.
We here report the rare case of a 64-year old male patient, with PWCD. The patient suffered from rheumatoid arthritis for several years, but then developed relapsing fever and recently occurring painful subcutaneous nodules predominantly at the inner part of his left upper limb with no signs of synovitis. Finally, a biopsy from one of the nodules revealed lobular panniculitis with mixed cell infiltrate, which was conformable only with PWCD, after excluding several differential diagnoses. In our patient PWCD developed despite immunosuppressive therapy with steroids and different disease modifying drugs, which the patient received to treat his underlying rheumatoid arthritis. However, when DMARD therapy was switched to Ciclosporin A the patient's symptoms resolved.
Our observation supports the hypothesis that T cells are involved in the pathogenesis of PWCD. Thus, T cell modifying drugs should be primarily used to treat patients with this rare disorder.
Pfeifer-Weber-Christian Disease (PWCD) is a rare inflammatory disorder of subcutaneous adipose tissue. It is also known as ideopathic relapsing febrile lobular non-suppurative panniculitis and is characterized by recurrent subcutaneous inflammatory painful nodules, fever, and malaise due to systemic inflammation. PWCD is an exclusion diagnosis, when no other cause of the lobular panniculitis can be identified. The most important other causes of lobular panniculitis include systemic lupus erythematosus, α1-antitrypsin deficiency, lymphoma, trauma, pancreatitis, and certain types of infections (for review see [1, 2]). The characteristic painful nodules are observed primarily in the area of the lower extremities and the trunk. It is still debated if PWCD exists as a unique disease entity or if it is just a substitute for any lobular panniculitis with unknown cause. The reason for this debate is that, having more medical knowledge and better diagnostic tools, many of the cases of idiopathic lobular panniculitis diagnosed with so-called PWCD have other underlying causes [1, 3, 2]. However, we here present the case of a 64-year old male patient with relapsing febrile lobular non-suppurative panniculitis with mixed cell infiltrate of unknown origin. Even after extensive diagnostic procedures we could not identify any of the known causes of lobular panniculitis. We therefore diagnosed a PWCD and successfully treated the patient with Cyclosporin A. The case supports the hypothesis that PWCD is a T cell mediated autoinflammatory condition.
Here, we report the rare case of a 64-year old male patient with rheumatoid arthritis, relapsing fever and recently occurring painful subcutaneous nodules predominantly at the inner part of his left upper limb.
Here, we report the rare case of a Pfeifer-Weber-Christian syndrome, which responded well to therapy with prednisolone and cyclosporine A.
The diagnosis of a Pfeifer-Weber-Christian disease (PWCD) is depending on the presence of relapsing fever, systemic inflammation and panniculitis. However, due to the rarity of this condition it is still under debate, if PWCD is a unique disease entity, or if it is just a substitute for every panniculitis that does not fit a common diagnosis . This uncertainty might be the result of the fact that this disease entity has not been described in a monolithic way, and the original cases reported by Pfeifer, Weber and Christian differed slightly from each other . Pfeifer in 1892 first described multiple areas of atrophy in subcutaneous fatty tissue with no further specification . Weber described a "relapsing, non-suppurative panniculitis" in 1925 , and Christian in 1928 pointed out its febrile character . However, this can also be regarded as a process of refining symptoms resulting in the symptom complex of fever, systemic inflammation and lobular panniculitis of relapsing character, to finely define PWCD. With respect to the histological findings in panniculitis, an attempt was made to categorize nodular panniculitis into different histologically defined subtypes according to the pattern and composition of the inflammatory infiltrate . PWCD has been classified as lobular panniculitis with mixed cell infiltrate, which contrasts findings in erythema nodosum classified as predominantly septal panniculitis .
Unfortunately, in several reported cases the diagnosis of PWCD was solely based on histological findings . However, in our opinion diagnosis should always be based on clinical and histological findings, which might facilitate the recognition of PWCD as unique disease entity. Of course, the described symptoms together with lobular panniculitis can also occur in other diseases such as infections, certain malignancies, alpha-1-antitrypsin deficiency, pancreatitis, systemic lupus erythematosus and cytophagic histiocytic panniculitis, rendering PWCD an exclusion diagnosis following careful evaluation of the patient. However, all of these disease entities, except alpha-1-antitrypsin deficiency, were excluded in our patient by extensive diagnostic evaluation favouring the diagnosis of a PWCD (see above). We did not explicitly exclude alpha-1-antitrypsin deficiency, because panniculitis is only observed in patients with severe forms of the disease [2, 8], which would include other symptoms, like COPD and/or liver cirrhosis. However, our patient didn't show these symptoms and responded well to immunosuppressive therapy, which would not improve panniculitis due to alpha-1-antitrypsin deficiency.
Treatment of PWCD is also controversial, which might again be attributed to the fact that clear diagnostic criteria have not yet been established. Thus, it does not surprise that there are several treatment options reported in the literature mostly in the form of case reports. However, the best evidence exists for cyclosporine A and corticosteroids [9–17]. Our patient improved rapidly following cyclosporine A and corticosteroid treatment. Cyclosporine A is classified as a calcineurin inhibitor predominantly inhibiting IL-2 production and transduction of antigen-recognition signals in activated T cells . In the here reported case, leflunomide, methotrexate and sulfasalazine, despite displaying a broader range of immunosuppressive activity by interacting with multiple signaling pathways in various cell types, were not effective . Thus, even though the pathogenesis of PWCD is not finally resolved, the fact that the patient only responded to cyclosporine A points towards a predominant involvement of T-cells in the disease process.
In conclusion, this case report supports the hypothesis that PWCD is a T-cell mediated inflammatory disorder. Therefore, in our opinion, patients with PWCD should primarily be treated with T-cell modifying agents. However, it is still controversial if PWCD exists as a separate disorder or if the characteristic symptoms and inflammatory patterns are just a manifestation of an other underlying cause. Therefore, consideration of PWCD has to be based on a broad diagnostic procedure to exclude all likely differential diagnoses of lobular panniculitis, like infections, certain malignancies, alpha-1-antitrypsin deficiency, pancreatitis, systemic lupus erythematosus and cytophagic histiocytic panniculitis.
Written informed consent was obtained from the patient for publication of this case report and accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.
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