[CIS PIDD] [cis-pidd] therapy refractory ILD in immunodeficiency syndrome not fullfillimg criteria CVID

[CIS-PIDD]

Dear all,
Hope I may consult you with the following quite extensive but difficult case:

Currently I am treating a Caucasian woman, 66 y old, who presented elsewhere with an ILD in 2010. Concurrently she had repetitive upper and lower respiratory tract infections and low IgA, IgM, IgG2 subclass deficiency and lymphocytopenia (0.3*10-9). Her past medical history shows she is a DES daughter and was known with premature ovarian failure at 30. VATS was conducted in 2010 and histology of the lung tissue showed an image characteristic of extrinsic alveolar alveolitis, more than of GLILD (mixed lymphocytic infiltrate, intra-alveolar tissue macrophages with not well organised granulomas with giant cells and limited fibrosis). The PA specimens were even judged at Brompton. Nevertheless the patient did not have precipitins or exposure to defined allergens/ circumstances. She was treated with steroids (max 40 mg prednisone) for over a year and her pulmonary image was better. In 2011 she had a work-up for CVID and Pneu23 responses were borderline (2 mo after discontinuation of steroids). Since an internist at that time presumed CVID with ILD, she was treated with scIg since 2012, later high dose because of progressive lung disease. Over the time she developed alopecia, vitiligo, conjunctivitis, and more recently erythema nodosum, mucosal dryness, and photosensitivity. In addition she developed progressive splenomegaly which is currently 20 cm in size. She also developed nightsweats, peaking fevers, malaise and weight loss (10 kg). Bone marrow aspiration and biopsy because of mild m proteinemia showed no myeloproliferative syndrome or malignancy. PET CT scan showed increased intensity of spleen and bonemarrow and EN skin lesions.  HRCT of the lungs showed progression of the ILD image, predominantly located in lower lung fields, radiologically more suggestive of NSIP. Serologically she has signs of immune dysregulation without evident symptoms (after cessation of scIG): increased dsDNA binding, positive PR3 ANCA, low C4 and C1q, low titer positive ANA. After temporary cessation of scIg, the IgG levels did not drop below normal. IgA en IgM are deficient. Her Cd4 (40), Cd8 (80) and B cell (12) counts are extremely low, but it could be that cells are pooled in spleen and lungs. There are no (opportunistic) infections. Because a hematologic malignancy could not be proven, we decided because of deteriorating pulmonary function, to treat the patient with cyclophosphamide pulses 750 mg/m2 (6x monthly) and prednisone 60 mg with tapering. At this point she has had 3 infusion and is tapered to 30 mg of prednisone. Nevertheless the night sweats, malaise and spiking fevers have returned after taper of steroids below 45mg and so far no infection could be proven. I am waiting for a repeat of the HRCT of the lungs, but feel that current treatment is failing.

I am considering to switch the current therapy to rituximab 4x375mg/m2 weekly and azathioprine. Despite that patient does not officially classify for CVID, neither for a distinctive systemic autoimmune disease like SLE or ANCA vasculitis, most likely I still think het ILD should be put in a context of a immunodeficiency syndrome with extensive immune dysregulation. So far a hematologic malignancy cannot be proven; in addition the patient has been (progressively) ill for over 6 years now.

What is your advice? Would you continue an immunosuppressive regimen containing steroids or without steroids?

Many thanks
Helen


Met vriendelijke groet,

Helen Leavis, MD PhD

[Universitair Medisch Centrum Utrecht]

Internist-Klinisch Immunoloog | Reumatologie en Klinische Immunologie | Universitair Medisch Centrum Utrecht
Kamernummer F 02.133 | Huispostnummer F 02.126 | Postbus 80555 | 3584 CX UTRECHT
T +31 (0)88 75 555 55 | F +31 (0)30 2523741 | www.umcutrecht.nl<http://www.umcutrecht.nl/>
Afwezig: woensdagmiddag



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