Monday, February 6, 2012

Granulomas, necrotic pseudotumors post revision.....what is the story on this? (part 3 of x)

The last 3 posts have addressed possible issues that may develop after hip surgery.  Some of the journal articles claim that they (growths) develop after a revision surgery.  I am trying to understand what these growths/tumors/pseudotumors/necrotic granulomas etc....are and what the implication of them might be to patients like us.

I found one journal article published 2008  that claimed they might be a result of type IV immune response:
The clinical, morphological and immunophenotypic features of these necrotic granulomatous pseudotumours, which in all cases develop following a second resurfacing hip arthroplasty, is suggestive of a type IV immune response, possibly to MoM metal alloy components.

A subsequent journal article published in 2010 questioned that conclusion by researchers from the same institution. albeit two years later:  Oxford University in England:

However, lymphocyte reactivity to Co, Cr, and Ni did not significantly differ in patients with pseudotumors compared to those patients without pseudotumors. This suggests that systemic hypersensitivity type IV reactions, as measured by lymphocyte proliferation response to these metals, may not be the dominant biological reaction involved in the occurrence of the soft tissue pseudotumors.

I then uncovered this journal article in 2008 (same time as the first journal article above which  claimed another origin for these so called tumors:)

J Orthop Surg Res. 2008 Feb 13;3:6.

Th1 type lymphocyte reactivity to metals in patients with total hip arthroplasty.


Department of Orthopedic Surgery, Rush University Medical Center, Chicago, IL 60612, USA.



All prostheses with metallic components release metal debris that can potentially activate the immune system. However, implant-related metal hyper-reactivity has not been well characterized. In this study, we hypothesized that adaptive immunity reaction(s), particularly T-helper type 1 (Th1) responses, will be dominant in any metal-reactivity responses of patients with total joint replacements (TJAs). We tested this hypothesis by evaluating lymphocyte reactivity to metal "ions" in subjects with and without total hip replacements, using proliferation assays and cytokine analysis.


Lymphocytes from young healthy individuals without an implant or a history of metal allergy (Group 1: n = 8) were used to assess lymphocyte responses to metal challenge agents. In addition, individuals (Group 2: n = 15) with well functioning total hip arthroplasties (average Harris Hip Score = 91, average time in-situ 158 months) were studied. Age matched controls with no implants were also used for comparison (Group 3, n = 8, 4 male, 4 female average age 70, range 49-80). Group 1 subjects' lymphocyte proliferation response to Aluminum+3, Cobalt+2, Chromium+3, Copper+2, Iron+3, Molybdenum+5, Manganeese+2, Nickel+2, Vanadium+3 and Sodium+2 chloride solutions at a variety of concentrations (0.0, 0.05, 0.1, 0.5, 1.0 and 10.0 mM) was studied to establish toxicity thresholds. Mononuclear cells from Group 2 and 3 subjects were challenged with 0.1 mM CrCl3, 0.1 mM NiCl2, 0.1 mM CoCl2 and approx. 0.001 mM titanium and the reactions measured with proliferation assays and cytokine analysis to determine T-cell subtype prominence.


Primary lymphocytes from patients with well functioning total hip replacements demonstrated a higher incidence and greater magnitude of reactivity to chromium than young healthy controls (p < 0.03). Of the 15 metal ion-challenged subjects with well functioning total hip arthroplasties, 7 demonstrated a proliferative response to Chromium, Nickel, Cobalt and/or Titanium (as defined by a statistically significant >2 fold stimulation index response, p < 0.05) and were designated as metal-reactive. Metals such as Cobalt, Copper, Manganese, and Vanadium were toxic at concentrations as low as 0.5 mM while other metals, such as Aluminum, Chromium, Iron, Molybdenum, and Nickel, became toxic at much higher concentrations (>10 mM). The differential secretion of signature T-cell subsets' cytokines (Th1 and Th2 lymphocytes releasing IFN-gamma and IL-4, respectively) between those total hip arthroplasty subjects which demonstrated metal-reactivity and those that did not, indicated a Th1 type (IFN-gamma) pro-inflammatory response.


Elevated proliferation and production of IFN-gamma to metals in hip arthroplasty subjects' lymphocytes indicates that a Th1 (vs. Th2) type response is likely associated with any metal induced reactivity. The involvement of an elevated and specific lymphocyte response suggests an adaptive (macrophage recruiting) immunity response to metallic implant debris rather than an innate (nonspecific) immune response

from Connie:  I will try to navigate the literature (somehow) to figure out the difference between the adaptive immune response and the innate immune response, the type IV immune response and the Th1
type pro inflammatory response.

If anyone has these tumors or comes across them, I think it is critical that you, the patient know enough to ask some questions lest you find yourself on a cancer quest with an oncology group.  This is important stuff for me so I am just trying to share what I find in this arena.  I don;t know if this stuff is cancerous or not but it surely has to be defined so someone can determine what they are in a clinical setting.  The clinicians who practice outside of the orthopedic arena do not have a background in this metal stuff.  You must become informed on your own if you are deal with issues like experience.

I hope you don't have to deal with these issues of course!

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