EXPERIMENTAL AND CLINICAL TRANSPLANTATION

Key words : Acquired perforating dermatosis, Continuous ambulatory peritoneal dialysis, Immunosuppression

Perforating folliculitis is one of a rare group of skin conditions that typically affects patients with chronic kidney disease and diabetes mellitus.¹ In 1989, Rapini and colleagues described this condition under an umbrella term: acquired perforating dermatosis (APD).²

Perforating folliculitis has been reported more commonly in patients who are undergoing peritoneal dialysis.³ Case reports are scanty with regard to perforating folliculitis. Two cases have been described: the first from 1989 detailing a patient who had acquired immunodeficiency syndrome and
end-stage renal disease together with perforating folliculitis, and another describing a patient who had tuberculosis and was diagnosed with perforating folliculitis.^4,5 There was also a case study that highlighted an association between APD and certain drugs.⁶

In our review of the literature, we only found 2 case studies where an APD occurred in renal transplant recipients. In the first case study, a patient had persistent renal failure after transplant. In a second study of 2 transplant recipients, both had normal renal function; however, 1 patient had diabetes mellitus, and the other patient had hepatitis C virus.^1,7

We obtained consent from the patient and his mother to allow us to report on this case. The patient was an 18-year-old man who was initially referred to our hospital, Inkosi Albert Luthuli Central Hospital renal unit, in October 2017, at the age of 17. He was natively from Lesotho but grew up in the Gauteng province of South Africa. His primary language was Sesotho.

He was referred to us from a regional hospital and had a history of anasarca, as well as hematuria for 4 weeks before presentation. He reported no flu-like or febrile illnesses preceding presentation. He required emergency renal replacement therapy in the form of 2 sessions of hemodialysis at the regional hospital before being transferred to our unit.

Results of viral screening for human im-munodeficiency virus (HIV) and hepatitis A, B, and C were negative. Results of autoimmune screening for lupus and vasculitis were negative. Normal comple-ment levels were noted. His initial hemoglobin level was 6.5 g/dL, and his urea level was 14.7 mmol/L with a creatinine level of 586 μmol/L (Table 1).

Treatment with hemodialysis was continued while the patient awaited consideration for the chronic renal replacement therapy provincial program in KwaZulu-Natal, South Africa. A permanent hemodialysis catheter was inserted into the right internal jugular vein 1 week after admission.

While awaiting further investigations and procedures, the patient developed thrombocytopenia, precluding us from performing a renal biopsy. He then developed generalized tonic-clonic seizures, which lasted about 2 minutes, in December 2017. His blood pressure preceding the seizure was elevated at 171/111 mm Hg. Computed tomography of the brain showed no intracranial bleed or other abnormalities. A kidney biopsy was never performed due to persistent abnormal thromboelastograms.

The next day, an itchy red rash appeared over his face and chest, which was described as a papular eruption on an erythematous base. Primary varicella zoster virus (VZV; chicken pox) was suspected, which was confirmed with positive results of VZV DNA polymerase chain reaction and tests for immunoglobulin M antibodies. This was successfully treated with intravenous acyclovir (250 mg daily) together with calamine lotion and antihistamines.

At a follow-up visit in our hemodialysis unit in late February 2018, he complained of a 2-day history of generalized non-itchy rash that started on the face and progressed to cover the entire body. He reported no fever but did note a sore throat. The dermatology department made a clinical diagnosis of follicular eczema and advised treatment with a steroid ointment and follow-up on his response to therapy. No details of resolution or follow-up were noted.

He was then assessed for treatment with peritoneal dialysis and was deemed suitable. A Tenckhoff catheter was inserted into his peritoneum in late March 2018 without complications.

In late July 2018, after unsuccessful treatment with oral flucloxacillin, the patient developed a Tenckhoff catheter tract abscess that required formal debridement in the operating theatre. Continuous ambulatory peritoneal dialysis was continued despite the debridement. The abscess had not extended beyond the distal deep cuff. However, he then developed continuous ambulatory peritoneal dialysis peritonitis, and subsequent cultures indicated that this was caused by Staphylococcus aureus that was sensitive to cloxacillin and vancomycin. Vancomycin administered via the intraperitoneal route was continued for 21 days due to the unavailability of cloxacillin. The inpatient therapy lasted 2 weeks, and then injected peritoneal dialysis bags were taken home by the patient to complete the last week of therapy as an outpatient. His peritoneal dialysate white blood cell count peaked at 772 cells/μL and dropped to 0. He then developed Enterococcus faecalis-associated peritonitis in January 2019, and he completed an outpatient course of intraperitoneal vancomycin. His peritoneal dialysate white blood cell count peaked at 664 cells/μL and then dropped to 0.

In March 2019, he developed a Tenckhoff catheter exit site infection, which resolved with oral flucloxacillin. A nasal swab confirmed he was a Staphylococcus nasal carrier, and he was advised to perform strict handwashing and to avoid nose picking.

The superficial cuff of the Tenckhoff catheter was noted to be exposed on April 2019. Topical mupirocin was applied, and the exit site healed.

Results of pretransplant blood tests revealed the following: hemoglobin, 7.1 g/dL; sodium, 129 mmol/L; potassium, 3.0 mmol/L; chloride, 89 mmol/L; bicarbonate, 23 mmol/L; urea, 24.3 mmol/L; creatinine, 1222 mmol/L; and estimated glomerular filtration rate (eGFR), 4 mL/kg/m2. Results of viral screens for HIV, hepatitis B and C, and cytomegalovirus were negative (Table 1).

A kidney from a deceased donor became available in late June 2019, with a HLA match of 4/6, and he underwent kidney transplant the same day. Induction immunosuppression comprised immediate administration of basiliximab (4 mg intravenously), followed by tacrolimus (3 mg twice daily), mycophenolate mofetil (250 mg twice daily), and prednisone (30 mg once daily). Administration of ciprofloxacin was started empirically because double J stents were left in situ. On day 4 posttransplant, he received the second dose of basiliximab. His urine output steadily increased to 7 L per day, and his eGFR normalized on day 4 posttransplant. He was transitioned to drinking 5 L of water orally, and his tacrolimus levels were optimized. His tacrolimus level only reached a therapeutic level day 23 posttransplant because a conservative approach had been taken to reach the therapeutic level.

On day 10 posttransplant, he developed a papular eruption over the chest, face, and forearms (see Figure 1). Renal function at this stage had significantly improved: serum sodium was 146 mmol/L, potassium was 4.1 mmol/L, chloride was 118 mmol/L, bicarbonate was 22 mmol/L, urea was 5.0 mmol/L, creatinine was 131 mmol/L, and eGFR was >60 mL/kg/m2 (Table 1). Results of herpes simplex virus polymerase chain reaction test and a test for parvovirus B19 were negative. The consideration at this stage was that of steroid-induced acne. A pus swab revealed no growth on culture. Dermatologists were consulted and opted to treat for Staphylococcus-induced folliculitis with topical mupirocin (Bactroban). A nephrologist added treatment with doxycycline for acne. The dose of prednisone was not adjusted. Screening for VZV at this point was negative. The lesions did not progress in distribution or severity.

The patient was then discharged for follow-up at the transplant clinic, where dermatologists and a nephrologist were going to do individual follow-up visits. At 1 week after discharge, the skin lesions became umbilicated, and the dermatologists arranged a skin biopsy to rule out Molluscum contagiosum. At the subsequent weekly follow-up visit to the clinic, the histology of the skin lesions revealed perforating folliculitis, as shown in Figure 2. Administration of doxycycline was stopped, and treatment with 5% urea commenced. Retin A was unavailable. The lesions were resolving by this stage. His urea, creatinine, and electrolyte levels remained normal and on an ever-improving trend at each visit. Four months posttransplant, the skin lesions had almost resolved completely (see Figure 3).

There are 4 classes of perforating disorders of the skin: elastosis perforans serpiginous, reactive perforating collagenosis, perforating folliculitis, and Kyrle disease.¹ The pathogenesis of APD is unknown; however, microtrauma from scratching has been found to be the most common precipitant, and microvasculopathy from diabetes has also been implicated.⁸ No reports of local South African studies were found regarding the prevalence of APD. Although APD can occur before dialysis initiation, it more commonly occurs after a patient is placed on dialysis.³

Pruritus is reportedly the most common symptom of this condition.⁸ Thus excoriation and crusting are common presenting signs, with new skin lesions that may emerge due to Koebnerization.⁹ Skin biopsy is necessary to detect the transepidermal elimination of various substances and to establish a diagnosis.¹⁰ In pruritus associated with inflam-matory skin diseases, corticosteroids are the first-line therapy, with the more preferred route being topical therapy. Hydrocortisone has been found to reduce symptoms in pruritus of unknown etiology.¹¹ Topical calcineurin inhibitors have also been found to be effective in treating pruritus.¹² Renal transplantation has usually been found to resolve this condition; however, there are insufficient data to support this narrative.¹³ If primary therapy based on topical corticosteroids, antihistamines, or antibiotics fails, treating physicians should consider using another systemic treatment with allopurinol instead.¹⁴

A case study by Hurwitz and colleagues looked at the evolution of perforating folliculitis in 6 patients, with special attention paid to clinical and histological changes.¹⁵ The investigators found that the earliest lesions were follicular pustules, which evolved into perforating folliculitis that eventually turned into prurigo nodularis. These patients responded well to treatment with a combination of topical corticosteroids oral antistaphylococcal antibiotics and phototherapy.¹⁵

What is most remarkable in our case is that, although the patient had undergone peritoneal dialysis in the past, he had never had a similar episode in the past. According to our search, the most common symptom that is associated with perforating folliculitis is excruciating pruritus, which is noted to be linked to the pathogenesis of this condition. However, our patient had never complained of pruritus before, nor at the time that he developed signs of the eruption.

Most of the cases of APD reported in the past have involved patients who were undergoing peritoneal dialysis or hemodialysis. Only 3 cases were found in our search in which the patients had perforating folliculitis, and each one had pruritus.¹⁴

In the literature, we found that immuno-suppressive agents such as calcineurin inhibitors and corticosteroids have an antipruritic effect, and this may explain why our patient did not have pruritus.1^0.12.14 We are aware of cases where this condition has occurred in patients being treated with sirolimus; however, our patient was not treated with sirolimus, but rather with mycophenolate mofetil and tacrolimus.¹⁴

To our knowledge, there are only 2 case studies where APD occurred in renal transplant recipients.^1,7 The first case was a patient who had persistent renal failure after transplant. In the second study of 2 patients, both transplant recipients had normal renal function; however, 1 patient had diabetes mellitus, whereas the other patient had hepatitis C virus. These patients also presented with pruritic rash. The patient in our case had neither diabetes nor hepatitis C and had an asymptomatic papular rash, which is why we find it an intriguing case.

Perforating folliculitis is uncommon, and therefore clinicians should have a high index of suspicion for the condition. What was unusual in this case is that our patient developed a paradoxical APD while his urea and creatinine levels were on an improving trend. This may suggest that the etiology of APD may be due not only to a high creatinine level but that there may well be other uremic toxins/milieu that are not measured by the standard biochemical assay we are using. We also consider that the use of steroids and a calcineurin inhibitor may well have masked the symptoms of APD, which may explain the absence of symptoms in our case. This may make the diagnosis of APD difficult.

Volume: 20 Issue: 1 January 2022

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