[CIS PIDD] Fwd: Bruton patient with granulomatous skin disease

[Klaus Warnatz]

>> Dear all, 

>> 

>> I would appreciate diagnostic help in a male patient born in 1959 with a genetically proven M. Bruton who developed in 2011 a granulomatous skin disease of unknown origin. He associated it with the sickness of his lovebird (but no chlamydia were identified at that time, I don't think other pathogens were excluded). 

>> He had presented with a polyarthritis of finger, wrists and knees in 6/2011, as expected autoantibody negative, synovial fluid could not be obtained and a course steroids was started. Under this treatment while slowly tapering the steroids he developed the skin disease starting in the face, but also involving extremities, less the corso.  At this point we saw him the first time. Steroids had been stopped because of the skin reaction. For the arthritis no pathogen could be identified (no synovial fluid on joint tap) we nevertheless had started him on doxycycline was started but stopped after 2 weeks due to skin reaction without significant improvement. M Whipple was excluded subsequently  Afterwards we did not see him for one year but meanwhile we had asked for skin biopsies, which  confirmed granulomatous disease partly with central necrosis. First attempts to identify mycobacterial DNA were all negative for myc. tuberculosis as well as atypical mycobacteria. Due do the central necrosis in the granulomatous disease infectious origin was suspected but cultures of skin biopsies were negative. A PET CT was performed demonstrating increased metabolism in nearly all lymph nodes, the enlarged spleen and the bone marrow. 5 lymph inguinal nodes were removed and demonstrated granulomatous disease and in 1 of 5 the PCR fro atypical mycobacteria was positive but could not be further differentiated and the confirmative test was negative. the treating physicians decided to call it sarcoidosis and restarted steroids (this is about 1.5y after the first round) with 40mg/day. This led to improvement of the subfebrile temperatures and the general feeling, but not of the granulomatous skin lesions within the first two weeks. At this time we were contacted again because the blood cell counts worsened. The patient was leucopenic around 2ooo/nl and thrombopenic(around 40.000/nl) but dropped to 1.200 leukocytes and 20.000 thrombocytes. Steroids were stopped and the patient referred again to our hospital. Here we basically rebiopsied the skin lesions and the bone marrow. 

>> Histology was confirmed, all cultures negative (mycobacterial cultures are currently in the third week), multiplex PCR for eubacterial DNA, for fungal DNA, mycobacterial DNA, leishmania, chlamydia psittaci all negative. Beta D GLucan negative. Markers for granulomatous disease were elevated (sIl2R, ACE, Neopterin). We did not identify a lymphoma although the last clonality analysis from the skin biopsies is still pending. 

>> Lab results: Leucopenia: 49% neutrophils, 28% lymphocytes, 12% eosinophils (this was a persisting finding over the last 1.5 years, LDH within the normal range 

>> Bone marrow. regular differentiation of the white and red cells, normal megakaryocytes, eosinophilia, no signs of malignancy, no increased lymphocytic infiltration

>> Microbiology: BM and skin biopsies: eubacterial, fungal, macobacterial, M Tub, Listeria, Bartonella, Toxoplasma PCRs all negative, 

>> blood CMV and EBV PCR eng cryptococcal Ag neg.

>> Immunstatus: Cd4 400/µl CD19 0, CD8 300/µl.

>> histology: adnexotrope granulomatous, partially necrotising inflammation (partiale with destruction of hair follicles) with increased lymphocytic infiltrates (IHC still pending),  PAS, Gram, Ziehl-Nelsen negative.

>> Because of the reaction to the steroids and the suspicion of a pathogen driven inflammation we decided to first put him on a course of azithromycin. after 2 weeks the blood cell counts had improved (leucocytes >3000 and thrombocytes > 70.000), but the patient is still having subfebrile temperatures and there is no change of the skin (may be not to be expected). 

>> our Questions are: 

>> 1) what is the differential diagnosis of granulomatous skin disease in a patient with Bruton's disease given the results mentioned above? (eosinophilia, partly granulomatous disease with central necrosis, etc)

>> 1b) is there a potential link with the sick love bird? 

>> 1c) is there a link to changing the patient from octagam to privigen (prolin?) a question asked by the patient?

>> 2) have we sufficiently excluded an infectious cause ? if not which other examinations should we perform?

>> 3) what is the next therapeutic step? can we dar to put him on etanercept? try steroids again despite the primary manifestation under steroid treatment and worsening of the blood cell counts under this treatment?

>> 4) any prophylactic treatment for xyz?

>> 

>> we appreciate your input, thanks

>> 

>> Klaus

>> 

>> 

>> Prof. Dr. med. Klaus Warnatz

>> 

>> UNIVERSITÄTSKLINIKUM FREIBURG

>> University Medical Center Freiburg

>> Center for Chronic Immunodeficiency

>> Division of Rheumatology and Clinical Immunology

>> 

>> Tel: +49-761-270-77640 / FAX -71000 / Pager: 12-7100

>> 

>> Breisacher Str. 117, 79106 Freiburg, Germany

>> klaus.warnatz at uniklinik-freiburg.de

>> http://www.uniklinik-freiburg.de/cci

> 


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