INTRODUCTION

Kaposi’s disease is an angioproliferative disorder whose onset is related to the human herpes virus type 8. It presents in four forms: classical, endemic, AIDS-associated, and iatrogenic. The iatrogenic form is relatively rare and may be induced by several immunosuppressive treatments, such as cyclosporine, methotrexate, and corticoids.

Sirolimus is an inhibitor of the mammalian target of rapamycin (mTOR), which, since its discovery, has found a wide range of therapeutic uses. It is currently used in organ rejection in patients with mild to moderate immunological risk undergoing renal transplantation.

However, over the last decades, and due to its immunosuppressive, anti-proliferative, and anti-angiogenic properties, numerous studies have been published on the use of sirolimus in other areas, and it has shown promising potential in the treatment of complicated vascular anomalies [1].

Herein, we present a case of corticosteroid-induced Kaposi’s disease that progressed well on sirolimus.

CASE REPORT

An eighty-year-old patient with a four-year history of rheumatoid arthritis, treated with 20 mg oral corticosteroids, presented with diffuse angiomatous lesions evolving over the past three years. A dermatological examination revealed confluent, maculopapular, angiomatous lesions dispersed on the limbs, buttocks, face, and retroauricular area (Figs. 1a and 1b), without the involvement of mucous membranes, appendages, or lymph nodes, with no evidence of general health deterioration.

Figure 1: (a) Angiomatous nodule in the inner eye corner. (b) Angiomatous nodules in the left retroauricular area.

A skin biopsy with HHV8 investigation showed vascular proliferation, spindle cells, and a lymphoplasmacytic inflammatory infiltrate with diffuse expression of HHV8. Digestive fibroscopy was normal, while a thoracic CT scan revealed multiple parenchymal and subpleural nodules and micronodules associated with subpleural septal thickening (Fig. 2). Corticosteroid therapy was discontinued, and the patient initially underwent 24 sessions of radiotherapy combined with paclitaxel, which were withdrawn due to neurological toxicity. Pulmonary involvement with restrictive syndrome and low DLCO (diffusing capacity of the lung for carbon monoxide) contraindicated the use of bleomycin. Subsequently, the patient was put on sirolimus at a dose of 0.15 mg/kg, followed by a daily maintenance dose ranging from 0.04 to 0.06 mg/kg for a duration of six months.

	Figure 2: Parenchymal and subpleural nodules as well as subpleural septal thickening.
	Figure 3: (a) Total regression of the nodule in the left inner eye corner.(b) Total regression of the angiomatous nodules in the left retroauricular area.

After six months of treatment, a favorable outcome was observed, characterized by the complete disappearance of the cutaneous lesions (Figs. 3a and 3b) and regression of pulmonary nodules (Fig. 4). As for adverse effects, the patient developed a low-volume pleurisy that resolved thereafter.

Figure 4: Regression of the parenchymal and subpleural nodules.

DISCUSSION

The unique aspect of our case was the use of sirolimus for corticosteroid-induced Kaposi’s disease with pulmonary involvement leading to a positive outcome.

The association between corticosteroids and Kaposi’s disease has been documented in several case reports, mostly in patients with rheumatoid arthritis, The onset of dermatological lesions varied between 25 days and 8 years of corticosteroid use [2]. In our patient, the onset occurred after one year of corticosteroid therapy.

The relationship between immunosuppression and Kaposi’s disease was first described in the population of organ transplantation on immunosuppressive treatments. The induction of a major state of immunosuppression in these patients through strong immunosuppressive drugs has reduced the incidence of acute rejection in kidney transplant patients yet has increased the risk of cancer and viral reactivation such as the HHV8 virus incriminated in the development of Kaposi’s disease, explaining the frequency of this condition in kidney transplant patients, hence the introduction of rapamycin [3].

Sirolimus, or rapamycin, was first described as an antibiotic of the macrolide family, isolated in 1975 from the filamentous bacterium Streptomyces hygroscopicus. Its immunosuppressive effects were only described in 1977. Its mechanism of action is related to the inhibition of the mammalian target of rapamycin (mTOR) protein, with blockage of interleukin-2-induced T-cell proliferation. This inhibition leads to the blockage of interleukin-2-induced T-cell proliferation, which subsequently reduces protein synthesis, induces apoptosis, inhibits cell migration, and decreases the expression of vascular endothelial growth factor (VEGF) [4].

Owing to its properties, sirolimus has demonstrated its efficacy in the treatment of Kaposi’s disease, specifically in kidney transplant patients. Nevertheless, its use has not been reported outside this context, and to our knowledge, our case is one of the rare cases reporting the use of sirolimus in Kaposi’s disease induced by corticosteroids [5].

Concerning the treatment, there is no universally standardized protocol in place. Consequently, recommendations and therapeutic approaches may exhibit variability among specialists. In our specific case, we adhered to the protocol suggested by the National Comprehensive Cancer Network [6].

As for adverse effects, sirolimus may cause hematological and endocrine disturbances such as diabetes and dyslipidemia. Pulmonary disorders such as pneumopathy and pleurisy may be observed during treatment and do not necessarily require the cessation of treatment [7], as was the case of our patient. Although no case of death related to its toxicity has been reported, strict clinical and biological monitoring is recommended.

CONCLUSION

Sirolimus offers a new therapeutic option for resistant Kaposi’s disease or in patients with contraindications to conventional treatments. However, large-scale prospective studies are needed to evaluate its efficacy and safety in these patients.

REFERENCES

1. Ahmed Messaoud A, Taibi L, Bouharati D, Ammar-Khodja A, Benkaidali I. Efficacitédu sirolimus dans la maladie de Kaposi. Ann Dermatol Vénéréol. 2012;139:B232.

2. Schottstaedt MW, Hurd ER, Stone MJ. Kaposi’s sarcoma in rheumatoid arthritis. Am J Med. 1987;82:1021-6.

3. Stallone G, Schena A, Infante B, Di Paolo S, Loverre A, Maggio G, et al. Sirolimus for Kaposi’s sarcoma in renal-transplant recipients. N Engl J Med. 2005;352:1317-23.

4. Swarbrick AW, Frederiks AJ, Foster RS. Systematic review of sirolimus in dermatological conditions. Australas J Dermatol. 2021;62:461-9.

5. Endo G, Nagata N. Corticosteroid-induced Kaposi’s sarcoma revealed by severe anemia:A case report and literature review. Intern Med. 2020;59:625-31.

6. NCCN Guidelines Version 1.2022 Kaposi Sarcoma. ://www.nccn.org/professionals/physician_gls/pdf/kaposi.pdf

7. Nguyen LS, Vautier M, Allenbach Y, Zahr N, Benveniste O, Funck-Brentano C, et al. Sirolimus and mTOR inhibitors:A review of side effects and specific management in solid organ transplantation. Drug Saf. 2019;42:813-25.