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Keywords:

  • acquired perforating dermatosis;
  • diabetes mellitus;
  • dialysis;
  • renal failure;
  • transepidermal elimination

Abstract

  1. Top of page
  2. Abstract
  3. Introduction
  4. Materials and methods
  5. Results
  6. Discussion
  7. References

Background  The term of acquired perforating dermatosis (APD) comprises the perforating dermatoses occurring in adult patients. Clinical and histological features of the disease are not uniform, and may resemble any of the four classic perforating disorders: elastosis perforans serpiginosa, reactive perforating collagenosis, perforating folliculitis or Kyrle's disease. Chronic renal failure and/or diabetes mellitus usually accompany this skin disease.

Objective  The aim of this study was to delineate the clinical and histopathological features of acquired perforating dermatosis and to investigate the potential relationship between this disease and associated conditions.

Methods  Twenty-two patients with acquired perforating dermatosis were enrolled in this study. Clinical findings of acquired perforating dermatosis and the spectrum of associated diseases were investigated. Haematoxylin and eosin sections were re-examined, and immunohistochemical stainings (elastic van Gieson and Masson trichrome stains) and periodic acid-Schiff stain were also used for histopathological evaluation.

Results  Different clinical types of lesions resembling reactive perforating collagenosis, perforating folliculitis or Kyrle's disease were observed. Histopathological features were consistent with any of the four types of perforating dermatoses. Most of the patients (86.4%) had at least one systemic disease. Chronic renal failure (72.7%) and diabetes mellitus (50%) were the most commonly associated conditions. Most of the patients with diabetes mellitus (90.9%) had chronic renal failure due to diabetic nephropathy. All of the patients with chronic renal failure were on dialysis treatment. The other associated conditions were hepatitis (27.3%), anti-HCV Ab-positivity (13.6%), hypothyroidism (9.1%) and tuberculosis lymphadenitis (4.5%). Of the 22 patients, 13.6% were otherwise healthy, and 9.1% were renal transplant recipients.

Conclusion  Clinicopathological findings of our study indicate that the cases with APD represent the broad spectrum of perforating disorders rather than the variants of the same disease. Although APD is frequently associated with diabetes mellitus and chronic renal failure, this skin disorder may also develop in patients with other systemic disorders, and in those without any medical problems. This skin disease is probably linked to dialysis treatment in patients with chronic renal failure due to diabetes mellitus or other causes.


Introduction

  1. Top of page
  2. Abstract
  3. Introduction
  4. Materials and methods
  5. Results
  6. Discussion
  7. References

Acquired perforating dermatosis (APD) is an uncommon cutaneous perforating disorder. It is characterized clinically by hyperkeratotic papules and nodules, and histopathologically by transepidermal elimination of various substances such as keratin, collagen and elastic fibres. The disease arises in adulthood, usually in association with diabetes mellitus (DM) or chronic renal failure (CRF).1 In recent years, however, it has also been reported in patients with various other disorders, such as malignant,2,3 hepatic4 and endocrinological disorders,4 AIDS,5 tuberculosis,6 pulmonary aspergillosis,7 neurodermatitis,4 atopic dermatitis8 and scabies.9

The clinical features and histological findings of APD may resemble any of the four classic perforating skin diseases; namely, elastosis perforans serpiginosa (EPS), reactive perforating collagenosis (RPC), perforating folliculitis (PF) or Kyrle's disease (KD).1 Several theories have been proposed for the pathogenesis of APD. Microtrauma due to pruritus and scratching,10 DM-related microangiopathy,11 epidermal or dermal change related to metabolic derangements,12,13 and deposition of substances that cannot be removed with dialysis14 are the most commonly proposed theories.

Previous studies on APD include case reports of a limited number of patients alongside literature reviews. In this study, we aimed to delineate the clinical and histopathological features of APD. Another goal was to document the potential relationship between APD and associated diseases. To our knowledge, this is the largest series from a single centre. We report on 22 cases with APD.

Materials and methods

  1. Top of page
  2. Abstract
  3. Introduction
  4. Materials and methods
  5. Results
  6. Discussion
  7. References

Patient population

The study included 22 patients (16 males and 6 females) who were evaluated and treated at the Başkent University Faculty of Medicine, Dermatology Department, Ankara, Turkey, for biopsy-proven perforating dermatosis between May 1997 and July 2003. Patients were identified by dermatopathology patient records, retrospectively. Sixteen patients had been referred from the dialysis unit of the nephrology department, and two from the renal transplantation unit. Four patients had first presented to the dermatology department because of the skin lesions.

Study design

The hospital files of the patients were reviewed, and the following clinical data were gathered from the medical records: age at diagnosis of APD, APD duration, clinical features and location of skin lesions, associated symptoms, family history of similar skin disease, presence of Koebner phenomenon, associated systemic diseases and their duration. The available haematoxylin and eosin sections were retrieved and re-examined, and histological findings were recorded. New sections were obtained from available paraffin blocks for histochemical stainings; elastic van Gieson and Masson trichrome stains were used to evaluate elastin and collagen elimination, respectively, and periodic acid-Schiff (PAS) stain was used to determine the thickening of the vessel walls in patients with DM.

Results

  1. Top of page
  2. Abstract
  3. Introduction
  4. Materials and methods
  5. Results
  6. Discussion
  7. References

The demographic characteristics of the patients and clinical features of the skin lesions for each case are given in Table 1. The mean age at diagnosis was 48 years (range 29–74 years). There was no family history of perforating dermatosis in any patient.

Table 1.  The demographic characteristics of the patients, and the clinical and the histological data of the lesions
PatientAge (y)/ SexDistributionClinical appearanceSymptomKoebner phenomenonEliminated materialHistopathological features
  1. Y, years; F, female; M, male; KD, Kyrle's disease; RPC, reactive perforating collagenosis; PF, perforating folliculitis; EPS, elastosis perforans serpiginosa.

137/FUpper-lower extremities, gluteal regionHyperkeratotic papules (fig. 1a)Pruritus+_KD-like (fig. 1b)
235/MScalp, face, neckErythematous, keratotic plugged, umbilicated papulesPruritus_CollagenRPC-like
340/MGluteal region, backKeratotic plugged, umbilicated papulesPruritus_CollagenRPC-like
445/MGluteal and lumbar region, backHyperkeratotic papules___KD-like
530/MUpper-lower extremities, gluteal region, scalp, backHyperkeratotic papulesPruritus+_KD-like
655/MDorsum of the handsErythematous, keratotic plugged, umbilicated papules__CollagenRPC-like
743/FUpper-lower extremities, trunkErythematous pustulesPain_CollagenPF-like
850/MLower extremities, back, dorsum of the hands and feetHyperkeratotic papules and nodulesPruritus+_KD-like
956/MBack, shoulders, thighHyperkeratotic papulesPruritus+_KD-like
1029/MUpper extremities, gluteal regionErythematous, follicular, infiltrating papules and pustulesPruritus__PF-like
1167/FBack, scalpHyperkeratotic papules and nodulesPruritus__KD-like
1274/MLower extremitiesKeratotic plugged, umbilicated nodulesPruritus_CollagenRPC-like
1354/MLower extremities, gluteal regionKeratotic plugged, umbilicated papules and plaques (fig. 2a)Pruritus+CollagenRPC -like (fig. 2b,c)
1446/MUpper and lower extremities, trunkKeratotic plugged, umbilicated papules and nodulesPruritus_CollagenRPC-like
1558/MUpper extremitiesPurple annular plaques__CollagenRPC-like
1631/MUpper and lower extremities, backHyperkeratotic papules and nodules___KD-like
1743/MAbdomen, back, chest, upper extremitiesErythematous, follicular, infiltrating papules and nodules (fig. 3a)Pruritus__PF-like (fig. 3b)
1862/MAuricleHyperkeratotic papule (fig. 4a)Pain_ElastinEPS-like (fig. 4b,c)
1943/FUpper and lower extremities, gluteal regionHyperkeratotic papulesPruritus+_KD-like
2052/FLower extremities, abdomenHyperkeratotic papulesPruritus__KD-like
2165/FUpper and lower extremities, trunk, scalpKeratotic plugged, umbilicated papulesPruritus_CollagenRPC-like
2241/MUpper and lower extremities, trunk, scalpHyperkeratotic papulesPruritus+_KD-like
image

Figure 1. (a) Kyrle's disease-like hyperkeratotic papules on the left arm of Patient 1. (b) Epidermal depression filled with keratotic plug admixed with cellular debris, and epidermal hyperplasia (staining: H&E, original magnification ×10).

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image

Figure 2. (a) Reactive perforating collagenosis-like keratotic, plugged, umbilicated papules and plaques on the lower extremities of Patient 13. (b) Cup-shaped invagination of the epidermis filled with a plug consisting of keratin and cellular debris (staining: H&E, original magnification ×10). (c) Transepidermal elimination of collagen bundles (stained blue) (staining: Masson trichrome, original magnification ×4).

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image

Figure 3. (a) Perforating folliculitis-like follicular, erythematous, infiltrating papules and nodules on the back of Patient 17. (b) Follicular dilatation with perforation in the follicular wall and perifollicular inflammatory infiltration (staining: H&E, original magnification ×5).

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image

Figure 4. (a) Hyperkeratotic papule on the helix of the right auricle of Patient 18. (b) Epidermal depression filled with keratotic plug admixed with cellular debris and epidermal perforation (staining: H&E, original magnification ×5). (c) EPS-like changes (increased, coarse and black-stained degenerated elastic fibres) in the dermis (staining: Elastic van Gieson, original magnification ×20).

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The number of APD lesions ranged from a few to many. Extensor surfaces of the lower extremities (72.7%) were the most commonly involved site, followed by the upper extremities (63.6%), trunk (59.1%) and head (27.3%). Multi-site involvement was noted in 16 patients (72.7%). Different types of lesions were observed. In 11 (50%) of the patients, the lesions were KD-like hyperkeratotic papules and nodules; in 7 (31.8%) RPC-like hyperkeratotic, plugged, umbilicated papules, nodules and plaques were apparent; and in 2 (9.1%) PF-like follicular, erythematous, infiltrating papules and nodules were seen (erythematous pustules were also present in one of these two patients with PF-like lesions). Isolated erythematous pustules were noted in 1 patient (4.5%), and annular, purple plaques were observed in 1 other (4.5%). Sixteen patients (72.7%) had mild to severe pruritus, and 2 (9.1%) had pain. Koebner phenomenon was present in 7 (31.8%) patients (Table 1).

Histopathological evaluations revealed four types of lesions (Table 1): (1) Histopathological features of 10 (45.5%) cases showed epidermal invagination filled with keratotic plug admixed with cellular debris and neutrophils. In biopsy specimens of these 10 patients, Masson trichrome and elastic van Gieson stains were negative in the epidermis and in the crater. Hence, the overall histological appearance in these 10 cases was consistent with KD. (2) Histopathological features of 8 (36.4%) cases showed cup-shaped invagination of the epidermis filled with a plug consisting of keratin, cellular debris and neutrophils. There were vertically orientated collagen bundles at the base of the lesions in three of these eight cases. Masson trichrome staining showed transepidermal elimination of the collagen in all eight cases. Elastic van Gieson stains were negative in the epidermis and in the crater. The overall histological appearance in these eight cases was consistent with RPC. (3) Histopathological examination of three cases (13.6%) showed follicular destruction with keratin and cellular debris, and perifollicular mononuclear or mixed type inflammatory infiltration. Histochemical stainings showed transepidermal elimination of minimal collagen in one of these three cases. The features were consistent with PF. (4) In the last case, haematoxylin and eosin sections showed cup-shaped epidermal invagination containing cellular debris, and increased, degenerated elastic fibres in the dermis. Histochemical stainings showed transepidermal elimination of elastic fibres and increased, coarse and degenerated elastic fibres in the dermis. The overall histological appearance in this case was consistent with EPS.

Different clinical types of skin lesions were evaluated in terms of the nature of transepidermally eliminated material. In 10 out of 11 KD-like hyperkeratotic lesions, neither collagen nor elastin was identified, which is consistent with KD. In one case, transepidermal elimination of elastin suggested EPS. In all seven RPC-like keratotic plugged, umbilicated lesions, transepidermally eliminated collagen was consistent with RPC. All skin lesions with the clinical features of follicular erythematous papules and nodules showed follicular destruction, which is consistent with PF. The histopathological diagnosis in the case of annular plaques was consistent with RPC, in the case of isolated erythematous pustules was consistent with PF. In diabetic patients, PAS staining did not reveal thickening of the vessel walls in the upper dermis underlying the lesions.

Nineteen (86.4%) patients had at least one systemic disease (Table 2). In 16 patients (72.7%), CRF was the most commonly associated condition, followed by DM in 11 (50%), hepatitis in 6 (27.3%) [hepatitis C in 3 (13.6%), hepatitis B in 2 (9.1%), steatohepatitis in 1 (4.5%)], anti-HCV Ab-positivity in 3 (13.6%), hypothyroidism in 2 (9.1%), and tuberculosis lymphadenitis in 1 (4.5%). Two patients (9.1%) were renal transplant recipients (RTRs).

Table 2.  The duration of acquired perforating dermatosis and associated conditions in 22 patients
PatientAPD durationCRF durationDialysis type/ durationDM type/ durationOther DM-related vasculopathy/durationHepatitis type/durationAnti-HCV Ab-positivity/ durationHypothyroidism/ durationTuberculosis lymphadenitisRenal transplantation
  1. APD, acquired perforating dermatosis; CRF, chronic renal failure; HD, haemodialysis; PD, peritoneal dialysis; DM, diabetes mellitus; IDDM, insulin-dependent diabetes mellitus; NIDDM, non-insulin-dependent diabetes mellitus; PVD, peripheral vascular disease; Mo, months; Y, years.

11 Mo5 yHD, 2 yIDDM, 20 yRetinopathy, 5 y, neuropathy, 3 ySteatohepatitis, 1 y_3 y3 Mo_
24 Mo3 yPD, 2 yIDDM, 14 yRetinopathy, 5 y, neuropathy, 3 y_____
32 y5 yHD, 3 y___3 y___
42 Mo____Hepatitis C, 2 y___4 y
51 Mo13 yHD, 13 y__3 y___
61.5 y28 yHD, 4 y__7 y___
71 Mo3.5 yHD, 3.5 y__Hepatits C, 1 y____
82 y6 yHD, 6 yNIDDM, 20 yRetinopathy, 6 y, neuropathy, 6 y, PVD, 6 y_____
91 Mo17 yHD, 2.5 yNIDDM, 17 yRetinopathy, 2 y, neuropathy, 2 y, PVD, 1 y_____
105 Mo__NIDDM, 4 y_____4 y
111 Mo4 yHD, 3 yNIDDM, 26 yRetinopathy, 3 y, PVD, 1 y_____
128 Mo6 yHD, 6 y_______
137 Mo3.5 yHD, 3.5 yNIDDM, 15 yRetinopathy, 4 y, PVD, 3.5 yHepatitis B, 8 Mo____
143 Mo3 MoHD, 3 MoNIDDM, 6 yRetinopathy, 4 y, neuropathy, 4 y, PVD, 4 yHepatitis B, 3 y____
156 Mo_________
164 Mo1 yHD, 5 Mo_______
172 Mo_________
183 Mo3.5 yPD, 3.5 yIDDM, 17 yRetinopathy, 4 y_____
192 Mo______7 y__
201.5 Mo_________
211 Mo17 yHD, 10 yNIDDM, 20 y_Hepatitis C, 5 y____
221 Mo10 yHD, 8 yNIDDM, 16 yRetinopathy, 10 y_____

All of the patients with CRF were on dialysis treatment (14 on haemodialysis, and two on peritoneal dialysis), and in all of them, the APD lesions appeared after the initiation of dialysis (Table 2). In 10 of 16 patients (62.5%) with CRF, the cause of kidney disease was DM, in 3 (18.7%) hypertension, in 2 (12.5%) glomerulonephritis, and in 1 (6.25%) polycystic renal disease.

Of the 11 patients with DM, 3 (27.3%) had insulin-dependent DM (IDDM), and 8 (72.7%) had non-insulin-dependent DM (NIIDM). Of these 11 patients, 10 (90.9%) had at least one type of DM-related complication: 10 (90.9%) had nephropathy, 9 (81.8%) had retinopathy, 5 (45.5%) had neuropathy, and five (45.5%) had peripheral vascular disease (PVD). In all patients with DM, the APD lesions developed many years (mean 15.4 years) after the onset of DM and after the initiation of all types of DM-related complications (i.e. nephropathy, retinopathy, neuropathy and PVD; mean 7.8 years, 4.8 years, 3.6 years and 3.1 years, respectively) (Table 2).

Discussion

  1. Top of page
  2. Abstract
  3. Introduction
  4. Materials and methods
  5. Results
  6. Discussion
  7. References

The cutaneous perforating disorders are a group of papulonodular skin disorders characterized by the transepidermal elimination of some components of the dermis.1 These disorders have traditionally been classified into 4 types: EPS, RPC, PF and KD. This classification is primarily based on the nature of the eliminated material and the type of epidermal disruption.12 In EPS, which generally begins in childhood as a genetically inherited disorder or in association with other genetic disorders, elastic fibres are eliminated through the epidermis; in RPC, a genetically inherited disorder that develops in childhood, there is transepidermal elimination of collagen bundles; in PF, degenerated follicular contents with or without collagen and elastic fibres are eliminated; and in KD, a controversial entity that is regarded as a late-onset genetically inherited disease or as a variant of PF, transepidermal elimination of keratotic material without collagen or elastic fibres is observed.12 Over the last two decades, the four major perforating disorders have also been observed in adult patients with CRF and/or DM as well as some other systemic disorders. The authors of these reports used many confusing terms such as EPS,15 acquired RPC,16 reactive perforating collagenosis of DM and renal failure,17 PF,14 PF of haemodialysis,18 KD,19 Kyrle-like lesions,20 uremic follicular hyperkeratosis,21 and perforating pseudoxanthoma elasticum.22 Later on, because of the close clinical and histopathological resemblance among these cases, it was suggested that they are the variants of the same disease process.23 Finally Rapini et al.24 recommended the term acquired perforating dermatosis for perforating skin disorders occurring in adult patients with systemic diseases. These authors indicated that this name would be quite appropriate for this condition, as the name avoids describing what material is being eliminated. Furthermore, it encompasses the broad spectrum of perforating disorders seen in association with systemic disorders.

In our study, we reviewed 22 cases of APD. The lesions of APD had varying clinical features resembling RPC (umbilicated erythematous papules with central keratotic plug), PF (erythematous follicular papules), and KD (hyperkeratotic papules and nodules). However, we did not observe any lesion that clinically resembled EPS. Interestingly, we observed annular plaques in one patient and isolated erythematous pustules in another, which did not resemble any of the four classic perforating disorders. The histopathological diagnosis in the case with annular plaques was consistent with RPC, whereas it was PF in the other with isolated erythematous pustules. The lesions were located mainly on the extensor surfaces of the extremities and the trunk. However, unusual presentations on the face, scalp and auricle were also observed. Multi-site involvement was also common. Pruritus, the usual symptom of APD,23 was present in 72.7% of our patients. Two patients had pain, which is an unexpected symptom for APD. Koebnerization, which is frequently reported in APD,1 was also observed in some members of our patient group. In patients with APD, trauma from scratching was proposed to cause epidermal abnormality12 or dermal collagen damage,10,25 resulting in transepidermal elimination. Frequent association of APD lesions with pruritus, localization of the lesions mostly on the trauma-prone areas, and presence of the Koebner phenomenon in some of our cases suggest that mild superficial trauma (e.g. scratching due to pruritus) may in fact be an important aetiological factor in the aetiopathogenesis of APD.

As previously stated in the literature, we observed histopathological features consistent with any one of the four classic types of perforating dermatoses. Kyrle-like histopathological features were the most common (45.5%), followed by RPC-like features (36.4%). Perforating folliculitis was also noted in three patients and EPS-like histopathological features in one patient. A previous study23 documented the lesions with histological features of PF, RPC and KD in the same patient. Moreover, Rapini and co-workers24 reported combined transepidermal elimination of both collagen and elastin in their four patients with APD. They proposed that varying histological findings in this disease may represent the different stages or different types of lesions in the same pathological process. However, we did not observe such overlapping histological features in our patient group. Therefore, it seems likely that the cases with APD represent the broad spectrum of perforating disorders rather than the variants of the same pathological process. On the other hand, in most of our cases, histopathological features were consistent with KD or RPC-like perforating disorders and there are only 3 cases with PF and a single case with EPS-like features. Thus, this conclusion is largely confined to KD and RPC but it may be invalid for the whole spectrum of APD. Moreover, it is also possible that we have been unable to observe the different stages of the histopathological evolution because of the fact that we have taken only one biopsy from each patient. However, on the basis of distinctive histopathological findings with the absence of overlapping histopathological features in our study we think that APD consists of four different types of perforating disorders, namely, KD, RPC, PF and EPS-like perforating disorders. In a previous study, both collagen and elastin were noted in the early, non-umbilicated lesions, whereas collagen was observed in the umbilicated ones. Fibrous component was the only material eliminated in the late lesions, probably due to the degeneration of both collagen and elastin. In contrast to these early findings, we observed neither collagen nor elastin elimination in most of the non-umbilicated lesions. However, collagen elimination was observed in the umbilicated ones, which was similar to the findings in the above-mentioned study.

Earlier reports have documented the association of APD with various systemic diseases, especially CRF, DM or both.4,11,23,26,27 Diabetes mellitus is reported to be the most frequent cause of CRF in APD patients.19,23,27 The majority (86%) of our patients had at least one systemic disease, and CRF (72.7%) and DM (50%) were also the most common diseases. Likewise, in more than half (62.5%) of the patients with CRF, the underlying cause of the kidney disease was DM. However, as has been noted in the literature,4,19,24,27 we also observed APD in non-diabetic patients with CRF. Acquired perforating dermatosis developed after the onset of CRF in all patients with CRF. Moreover, in all patients with CRF due to DM, APD occurred after the onset of CRF. Therefore, it seems that in our CRF patients with DM, the kidney disease rather than the DM itself had a causal relationship with APD. In the literature, epidermal12 or dermal abnormalities13 such as alterations in collagen or elastic fibres due to metabolic disturbances related to CRF have been suggested as underlying factors in APD patients with CRF. In a previous study,28 degenerated elastic fibres were observed at the base of the early lesions. However, the authors did not note any morphological evidence for the collagen abnormality. Later on, it was speculated that the collagen might have been biochemically but not morphologically altered in these patients.26,29 Another suggestion for APD pathogenesis in CRF is that the disease may be precipitated by dermal microdeposits of substances such as calcium salts, which are possibly a by-product of the CRF.27

Diabetes mellitus was the second most frequent (50%) disease associated with APD in the present study. Three of our patients had IDDM, and most (8) had NIDDM. Other investigators have also found that NIDDM is more frequent in patients with APD.4,26 In contrast, Morton and coworkers27 observed that APD is more often associated with IDDM compared with NIDDM. We reviewed all of the previous case reports of APD associated with DM and noted that most of them had at least one vascular complication of DM.7,11,13,24,26,27 Furthermore, in two previous studies,11,26 PAS-positive thickening of the vessel walls was found in the upper dermis in diabetic patients with APD. The authors of these studies proposed that trauma from scratching may cause dermal necrosis due to poor blood supply that results from vasculopathy, with necrotic dermal material then being extruded through the epidermis.11,26,27 On the basis of these findings, diabetic vasculopathy is considered to be an additional and important predisposing factor for APD in diabetic patients who scratch their skin.11,16,27 Although APD has been reported in previous studies to occur after the onset of nephropathy; there was no data about the relationship between the onset of APD and the other DM-related vascular complications.7,11,13,24,26,27 Ten of our 11 diabetic patients had at least one type of DM-related vascular complication (i.e. nephropathy, retinopathy, neuropathy and/or PVD), and in all of them, APD lesions developed after the onset of all types of vascular complications. However, we noted that nephropathy with or without other vascular complications was present in all these patients. Moreover, as we did not find thickening of the vessel walls in any of our 11 diabetic patients, it is likely that nephropathy itself rather than angiopathy may be the crucial factor in the development of APD in diabetic patients.

In patients with CRF, APD often occurs following dialysis;23,26,27 however, the lesions may also start in the pre-treatment period.19,23,27 Our 16 patients with CRF, undergoing either haemodialysis or peritoneal dialysis, developed APD after the initiation of dialysis treatment. This suggests that APD is probably linked to dialysis in most patients with CRF. Moreover, all the diabetic patients with nephropathy were also undergoing dialysis treatment, and APD lesions developed after the initiation of dialysis treatment in all of them. Therefore, APD in our diabetic patients seems likely to be related to dialysis treatment.

Acquired perforating dermatosis has also been reported in association with a wide variety of other systemic disorders (Table 3).2–9,30–39 However, most of the reported patients had also DM and/or CRF. Only in cases with lymphomas,2,3 pancreas carcinoma,31 hypothyroidism,4 myelodysplastic syndrome33 and AIDS36 there was no DM and/or CRF. Thus, the association of majority of systemic diseases and APD may be coincidental. In our series, different types of hepatitis (hepatitis C, hepatitis B, steatohepatitis), anti-HCV Ab-positivity, hypothyroidism and tuberculosis lymphadenitis were the other conditions noted in APD patients, and APD occurred after the onset of all these conditions. However, among these disorders only hypothyroidism and hepatitis C were observed in APD patients (each in one patient) without CRF and/or DM. It is known that renal transplantation clears APD.18,40 Interestingly, APD developed after renal transplantation in two of our patients. In the literature, there is only one case report of post-transplant APD13 in which the authors attributed the occurrence of APD in that patient to persistent renal failure. In contrast, renal functioning in our renal transplant patients was normal. However, one of these patients had DM and the other had hepatitis C. Thus, the possible causal role for hepatitis, anti-HCV Ab-positivity, hypothyroidism, tuberculosis lymphadenitis and renal transplantation in APD development should be confirmed by additional case reports. Finally, another unusual finding of this study was that APD was detected in three individuals in whom neither a systemic disease nor any other dermatological problem was observed. There are only five previous reports of APD occurring in otherwise healthy people.28,41

Table 3.  Literature review: systemic disorders other than diabetes mellitus and chronic renal failure associated with acquired perforating dermatosis
The diseases associated with acquired perforating dermatosisReference number
Hodgkin's disease2
Mixed histiocytic-lymphocytic lymphoma3
Liver carcinoma30
Pancreas adenocarcinoma31
Prostate carcinoma32
Myelodysplastic syndrome33
Hypothyroidism4
Sick euthyroid syndrome34
Hyperparathyroidism4
Neurodermatitis4
Hepatic dysfunction4
Primary sclerosing cholangitis35
Acquired immunodeficiency syndrome5, 36
Pulmonary aspergillosis7
Lupus vulgaris6
Atopic dermatitis8
Scabies9, 37, 38
Poland syndrome39

In conclusion, CRF and dialysis treatment are the conditions most frequently associated with APD, and APD is probably linked to dialysis in CRF patients. The strong association of APD with dialysis suggests that this patient group could be a valuable population for further study of the aetiopathogenetic mechanisms in the development of APD. Currently, we are planning a prospective study to investigate the ultrastructural changes and deposition of substances in both normal and diseased skin of APD patients by taking multiple biopsies. Acquired perforating dermatosis is also frequently seen in association with DM. It appears that dialysis treatment is the major factor in the development of APD in diabetic patients. This skin disease may also develop in patients with other systemic disorders and in patients without any medical problems. Further case reports or clinical studies will confirm the roles of other systemic disorders or factors in the development of APD.

References

  1. Top of page
  2. Abstract
  3. Introduction
  4. Materials and methods
  5. Results
  6. Discussion
  7. References