I am currently (5/6/2022) at the American Society for Apheresis (ASFA) annual meeting in Philadelphia presenting a poster titled “The Effects of Pulsed Therapeutic Plasma Exchange on Gastrointestinal Symptoms in Limited Systemic Sclerosis: A Case Series” . (The abstract of the poster is at the end of this post.) Six years ago, at this same conference, I presented an early version of the comprehensive review on the use of therapeutic plasma exchange as a treatment for systemic sclerosis that is now published in the “Journal of Scleroderma and Related Disorders” (http://dx.doi.org/10.1177/2397198318758606).
While there are a number of patients now on the pulsed therapeutic plasma exchange (PPE) protocol described in this article (http://sclerodermainfo.org/pdf/TPE-Guidelines-US.pdf), the focus of this paper is on four patients who have the same antibody/diagnosis (centromere/limited systemic sclerosis), and who have been on this protocol for periods of time ranging from about 1 ½ years to more than 29 years.
GI issues such as GERD are almost universal in patient with systemic scleroderma and many have additional GI symptoms including difficulty swallowing (dysphagia), delayed stomach emptying (gastroparesis), Gastric Antral Vascular Ectasia (GAVE) with blood loss, and Small Intestinal Bacterial Overgrowth (SIBO). Standard treatments such as immunosuppressive medications have no overall effect on GI symptoms, although many symptoms can be treated (with varying degrees of efficacy). While all four of these patients had significant improvements in other symptoms as well, what was striking was that all four also had significant improvements in GI symptoms including GERD and in one patient, GAVE.
Therapeutic plasma exchange (TPE) is commonly used to treat a number of disorders and has an excellent overall safety profile, with the only known long-term side effect being mild iron deficiency anemia (usually easily treated with over-the-counter iron supplements). The American Society for Apheresis classifies TPE to be a level III treatment when used as a treatment for systemic sclerosis, meaning that strong research such as recent clinical trials have not been done, but there is evidence suggesting that it may be effective and no contraindications. The best way to think about TPE as an experimental treatment for systemic scleroderma is as an “off label” label use of a standard treatment, as is also the case with medications such as methotrexate or mycophenolate mofetil (Cellcept), which are also not approved to treat systemic scleroderma.
Here are links to the poster itself and a much more detailed handout that will be used as the basis for an expanded version of this poster that will be submitted for publication in the near future:
Scleroderma Education Project Ltd
Background: Up to 90% of patients with systemic sclerosis (SSc) experience significant gastrointestinal (GI) symptoms such as gastro esophageal reflux disease (GERD), small intestinal bacterial overgrowth (SIBO), and Gastric Antral Vascular Ectasia (GAVE) with associated anemia. Conventional systemic treatments including immunosuppression have no effect on the development of severe GI symptoms. Previous research on the use of therapeutic plasma exchange (TPE) as a treatment for SSc has typically described clear improvements in clinical symptoms and laboratory markers with very few adverse events. However, there has been almost no documentation on the effects of TPE on GI symptoms. This case series documents the effects on GI symptoms in four patients diagnosed with limited cutaneous systemic sclerosis (lcSSc) who have been on a specific pulsed plasma exchange (PPE) protocol for 15 months to 28 years.
Methods: All patients received a one blood volume TPE treatment per week for four weeks using albumin as the plasma replacement. This was followed by eight weeks with no treatment before the next cycle of four weekly treatments. Clinical assessment tools included the Scleroderma Health Assessment Questionnaire (SHAQ) and the UCLA Gastrointestinal Tract survey (GIT 2.0). No patients are on concurrent immunosuppressants.
Results: Data are summarized in Table 1. All four patients showed significant improvement in GI symptoms, including significant reduction or complete elimination of GERD in two patients, sustained normalization of hemoglobin in a patient with GAVE who had required six ablations and three iron infusions prior to starting PPE, and nearly complete elimination of severe esophageal spasms in a fourth patient. Two patients reported significant reduction of pain and fatigue, and in one patient, significant improvement was observed in diffusing capacity for carbon monoxide (DLCO). No significant adverse events related to TPE treatments were reported in any patient.
Conclusion: While all four of these patients exhibited significant improvements in a variety of clinical signs and symptoms, the observed improvements in a broad spectrum of GI symptoms is significant, since conventional treatments do not lead to GI symptom improvements. Given that GI involvement can severely affect quality of life in patients with SSc and that previous research has demonstrated that TPE has an excellent safety profile, these preliminary results suggest that pulsed plasma exchange should be considered in lcSSc patients with significant GI symptoms. Additional research is needed to better understand the mechanisms of action for this treatment modality and whether they will replicate in SSc patients with different antibodies and clinical profiles.
(Note: Table 1 is included in the detailed Handout.)
1. Harris, E., Weiss J., Lacson S. (2022). The Effects of Pulsed Therapeutic Plasma Exchange on Gastrointestinal Symptoms in Limited Systemic Sclerosis: A Case Series. J Clin Apher, 37(2), 168.