CHALLENGES IN MANAGEMENT OF SCLERODERMA RENAL CRISIS: A FOCUS ON ACE INHIBITORS NON-RESPONSIVENESS AND ROLE OF PLASMA EXCHANGE

Introduction:

Scleroderma renal crisis (SRC) is the most feared, devastating and rare complication of systemic sclerosis. It is seen in around only 10-15% of cases of diffuse cutaneous and <2% of limited cutaneous disease. Typical presentation comprises, malignant hypertension, acute kidney injury and other organ injury due to elevated blood pressure.Thrombotic microangiopathic anemia can be seen in up to 50% of patients characterized by mechanical type of hemolytic anemia, thrombocytopenia, proteinuria and hematuria. Predictive factors for SRC include diffuse cutaneous disease, tendon friction rubs and use of glucocorticoids, anti-RNA polymerase III antibody. Angiotensin convertase enzyme inhibitors are first line treatment for scleroderma renal crisis despite the unavailability of randomized control trials. Even with the use of ACEi (ACE inhibitor), SRC has poor prognosis. And those not responding to above treatment have worst prognosis.However, for patient not responding to ACEi, there is no clear evidence for further management.

Methods:

Case report:A 27-year-old female with an initial diagnosis of limited cutaneous systemic sclerosis on oral methotrexate 15 mg/week and low-moderate dose oral glucocorticoids (for arthritis) presented with progressive skin tightening diffusely involving all 4 limbs, face and trunk and history of progressive shortness of breath over 4-5 months. She landed up in emergency with worsening shortness of breath now at rest (for 5 days) along with renal dysfunction, oliguria, palpitations, and chest pain. On evaluation she had microangiopathic hemolytic anemia (MAHA), thrombocytopenia, renal dysfunction, hypertension and evidence of myocarditis with cardiogenic pulmonary edema (Table 1). A provisional diagnosis of scleroderma renal crisis was made and patient was started on oral enalapril. BP control was achieved and there was an initial transient response in platelet count and schistocytes although the renal function remained static. On day 4 she had worsening of renal function (requiring renal replacement therapy), thrombocytopenia and MAHA despite adequate control of blood pressure.

 Results:

Alternate day Plasma exchange (PE) was started. Considering 3+ proteinuria, evidence of myocarditis and worsening on ACE-inhibitor, a possibility of overlap AAV or SLE was considered. Appropriate serological workup was sent and renal biopsy was planned. With 5 sessions of PE she had improvement in her symptoms, platelet count, MAHA and renal function (she became dialysis independent). Renal biopsy showed arteriolar thrombotic microangiopathic hemolytic anemia (TMA) suggestive of scleroderma renal crisis (SRC). Follow-up Echo showed resolution of cardiac dysfunction without institution of immunosuppression.

Conclusions:

SRC is characterized by development of malignant hypertension, acute kidney injury and MAHA, it can cause end organ damage of other critical organs like heart, lung and gastrointestinal tracts. Angiotensin convertase enzyme inhibitors (ACEi) are the 1st line agent despite the unavailability of randomized control trials. However, for patient not responding to ACEi, there is no clear evidence to guide further management. Various authors have suggested using PE in cases of ACEi non-responsiveness or TMA dominant picture. However, these suggestions are mostly based on limited case reports. One retrospective study comprising 20 patients with SRC used PE in combination with ACEi and showed better survival at 1-year followup compared to ACEi alone. However, not all subsets of SRC patients are likely to benefit from addition of PE. Additional studies are needed to identify the subset of SRC patients most likely to benefit from PE, and the precise role of combination ACEi and PE.

I have no potential conflict of interest to disclose.

I did not use generative AI and AI-assisted technologies in the writing process.