[CIS PIDD] [cis-pidd] Granulomatous disease in 64y patient with Bruton's disease

[Nacho Gonzalez]

Dear Klaus,

I follow a patient with agammaglobulinemia and "sterile" abscesses around
the neck, resembling granulomas. By 16S rDNA PCR and sequencing from
"sterile" neck and abdominal abscesses I identified a rare Mycoplasma
subespecies only sensitive to levo/moxifloxacin. Perhaps it is the reason
for the antibiotic unresponsiveness. Has your patient CD4 lymphopenia as
well?

Hope this helps,

Luis Ignacio Gonzalez-Granado
Immunodeficiencies. Pediatrics
Hemato-Oncology.
Hospital 12 octubre.
Madrid .Spain


2013/12/2 Klaus Warnatz <klaus.warnatz at uniklinik-freiburg.de>


> thanks that is very helpful, and you did not see any reactivation of any

> infection? How long do you have her (meaning that she is a CVID patient not

> gamma, correct?) on infliximab?

>

> greetings

>

> 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

>

> Am 02.12.2013 um 19:35 schrieb amalbran31:

>

>  I had a similar patient, reported in JCI, that went into remission with

> infliximab. She relapses every time I taper it. Best regards,

>

>  Alex Malbran

>

>

>  Enviado desde Samsung Mobile de Claro

>

> Klaus Warnatz <klaus.warnatz at uniklinik-freiburg.de> escribió:

>  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.

>

> Short version:

> The granulomatous disease was also identified in lymph node biopsy (PET CT

> positive all LN, bone marrow and spleen) (atypcial) mycobacterial infection

> was excluded on several occasions, pan fungal and eubacterial PCR were

> negative. No improvement on short term steroids (40mg pred/day for 2 weeks)

> which was stopped due to increasing cytopenia (thrombus 40.000-20.000 and

> Leukocytes 2.000-1.200). Subsequent thorough work up did not identify any

> pathogen or lymphoma. Azithromycin

> therapy for 3 weeks without improvement. Additional remarkable lab result:

> persistent eosinophilia of 10-15%.

> Happy to send photos of the skin lesions if wished for (not possible

> through the server).

>

> Our Questions see below!

>

> Long version:

> 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 to 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 for 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.

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

> Skin 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 dare 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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