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Background:
Case Report

Perforating Gout: Expanding the Differential for Transepidermal Elimination

by
Michal Bohdanowicz
and
Scott H. Bradshaw
*
Department of Medicine, Sunnybrook Campus, University of Toronto, 2075 Bayview Ave., Toronto, ON M4N 3N5, Canada
*
Author to whom correspondence should be addressed.
Dermatopathology 2023, 10(3), 207-218; https://doi.org/10.3390/dermatopathology10030029
Submission received: 25 May 2023 / Revised: 3 July 2023 / Accepted: 4 July 2023 / Published: 12 July 2023
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Abstract

:
Perforating dermatoses are dermatologic disorders with transepidermal elimination (TE) of dermal substances. While TE is typically associated with collagen and elastin, it can also occur as a secondary event in other processes, and it is important to keep a broad differential. We present a case of perforating tophaceous gout, which underscores the need for a thoughtful approach to perforating disorders. An updated review of recent literature is also presented.

1. Introduction

Perforating dermatoses are a group of dermatologic disorders characterized by transepidermal elimination (TE) of dermal substances, including collagen, elastin, and other connective tissue components [1]. Less commonly, perforation can be due to the elimination of other materials, including calcium, mucin, foreign bodies, and even cellular material such as melanocytes. Granulomatous inflammation can also lead to perforation, examples of which include granuloma annulare, sarcoid nodules, rheumatoid nodules, and granulomatous infections. The epidermal changes associated with TE can be a diagnostic pitfall, as superficial biopsies can mimic other entities such as squamous cell carcinoma.

2. Case Report

We present a biopsy from the knee of a 38-year-old man with a hyperkeratotic, non-healing lesion. On low power, there is marked pseudoepitheliomatous hyperplasia with a crust (Figure 1a). There is a central defect with downgrowth of the epidermis towards pale dermal deposits and TE of the deposits. On high power (Figure 1b), the deposits are composed of fluffy amphiphilic material, surrounded by a palisade of histiocytes. A diagnosis of perforating tophaceous gout was made.

3. Discussion

3.1. Approach to Perforating Dermatoses

In this case, ample material was provided by the clinician, and although there was clinical uncertainty, the histologic diagnosis was straightforward. This underscores the value of a generous biopsy, especially when an unusual diagnosis is present.
Perforating dermatoses are a group of dermatologic disorders characterized by the TE of dermal substances, including collagen, elastin, and other connective tissue components. Woo et al. [1] point out that not all material eliminated from the dermis through the epidermis represents TE. TE is characterized by a remodeling of the epidermis to form downgrowths towards abnormal material within the dermis. The epidermis envelops the abnormal material, and subsequent maturation of keratinocytes transports the material from the dermis to the epidermis. Multiple channels are thus formed by the remodeled epidermis.
This process is contrasted against a suppurative ulcer, which is characterized by the destruction of the epidermis and subsequent elimination of dermal material through a draining sinus or ulcer. Material from the dermis is eliminated, but it is not transported by keratinocytes through TE.
The issue gets confused as perforating dermatoses often have central zones where the epidermis is absent (i.e., ulcerated). The resulting ulcer will develop a crust and a neutrophilic inflammatory response to some degree. For TE, this neutrophilic inflammation should be a minor component rather than a draining abscess.
Returning to an approach to TE, the first step is to recognize the pseudoepitheliomatous hyperplasia as potentially representing the epidermal remodeling of TE. This can be challenging if the specimen does not include the full thickness of the epidermis. In addition, TE can mimic in-situ squamous cell carcinoma, both clinically, as in this case, and histologically, especially if the biopsy is superficial [2].
The second step in the approach is the examination of the eliminated substance. Again, a biopsy that transects the epidermis may not include the underlying substance. In our experience, this is commonly the case for biopsies to evaluate chondrodermatitis nodularis helicis versus squamous cell carcinoma. Although the diagnosis can typically be made on superficial biopsies, a sample including the entire epidermis is preferable.
Sorting causes of TE into categories provides an organized approach:
  • Endogenous substances (e.g., collagen, elastin)
  • Abnormal deposits (e.g., calcium, mucin)
  • Granulomatous disorders (e.g., sarcoid)
  • Cellular elimination (e.g., nevus)
The “primary” perforating disorders involve the elimination of endogenous dermal material (category 1 above). These include elastosis perforans serpiginosis, reactive perforating collagenosis, perforating folliculitis, and Kyrle’s disease. Although these conditions may share similar histologic features in terms of a mixed inflammatory infiltrate and hyperkeratosis, they differ in terms of their eliminated substance.
Elastosis perforans serpiginosa involves the TE of elastic fibers. The fibers may be subtle, and the diagnosis can be confirmed by identifying the presence of elastic fibers within the epidermis using special stains such as the Verhoeff-Van Gieson stain. Because elastosis perforans serpiginosis most often occurs on the lateral neck and flexural skin, the location of the biopsy is a helpful clue.
The perforating substance in reactive perforating collagenosis is collagen (Figure A1). In our experience, some patients exhibit extrusion of degenerating collagen and elastin into the crust overlying the ulcer in the early phase of wound healing after routine biopsies or excisions. It is therefore important to recognize that not all ulceration represents TE [1]. For a diagnosis of perforating collagenosis, there should be remodeling/invagination of the epidermis. Ideally, the extrusion of collagen and/or elastic fibers between keratinocytes in the intact epidermis adjacent to the ulcer can also be demonstrated, as shown in Figure A1.
The most common cause of perforating collagenosis is renal failure, but there are a number of other associations including diabetes, malignancy, rheumatoid arthritis, and other systemic diseases.
Kyrle’s disease is characterized by the TE of keratin and other materials. As with perforating collagenosis and elastosis perforans, there is often a history of diabetes or renal disease. There is longstanding controversy regarding the classification of Kyrle’s disease [2], specifically whether it represents a distinct entity or if it exists on a spectrum with the other TE disorders often associated with renal disease and/or diabetes [3]. We support the latter view, and our histologic reports use the umbrella term “acquired perforating dermatosis.”
Perforating folliculitis shows a similar pattern of TE of elastin and/or collagen, but the elimination channels are specifically associated with the follicular epithelium.
The remaining categories 2–4 are considered secondary causes of TE or perforation. Examples of these conditions include perforating granuloma annulare (Figure A2), perforating calcinosis, and perforating amyloidosis, among others (Table 1). Some entities reported to give rise to TE may belong to more than one category. For example, granuloma annulare has an abnormal accumulation of mucin, but the granuloma formation is felt to be the more important process leading to TE, thus it has been placed in the “granulomatous” category in the table. A similar argument applies to necrobiosis lipoidica and ochronosis. Conversely, while most infectious agents associated with TE do so through granuloma formation, botryomycosis does not typically show a prominent granulomatous reaction, and TE is more likely related to the elimination of the abnormal granule, putting it in the “abnormal deposit” category rather than the “granulomatous” category. This organism is associated with suppurative inflammation, and some cases of perforation may actually represent simple draining abscesses and not true TE.
Perforating pilomatricomas are also difficult to classify. This tumor characteristically shows rupture with an associated granulomatous reaction, and therefore it may fit into the “granulomatous” category. Dystrophic calcification is also common, which would put it in the “abnormal deposit” category along with calcinosis cutis and calcified elastic tissue. In some cases, the elimination appears to represent abnormal cells. As with all the entities in the granulomatous category, some cases may not represent TE at all but, in fact, be simple ulceration.
Several perforating diseases are caused by abnormal endogenous material. Calcified collagen or elastin can cause perforating calcific collagen or elastosis. Often, these are induced by the application of exogenous substances containing calcium.
Other perforating disorders are due to deposits of inorganic or organic material. The major inorganic material that perforates is calcium. Calcium can deposit in the dermis by different mechanisms, including dystrophic, metastatic, and idiopathic calcification. Perforating calcinosis cutis is likely on a spectrum with calcific collagenosis and elastosis depending on the degree of calcification. Many organic molecules can also deposit in the dermis and become targets for TE. Amyloid, a byproduct of misfolded proteins, is one such molecule. Most commonly, keratinocytes are the source of amyloid in perforating amyloidosis, and scratching is thought to be a major etiologic driver for these conditions. This deposition prefers colder areas of the body, like the skin. Homogentisic acid, on the other hand, accumulates in parts of the skin that have been exposed to chemicals like hydroquinone.
Exogenous material such as sutures, splinters, plant material, or glass is commonly perforated through the epidermis. In some cases, this may represent incidental drainage of an underlying abscess, but it may also induce a foreign body reaction that leads to granulomas and true TE, especially under conditions where the foreign material cannot be absorbed. Sarcoidosis is a systemic condition with idiopathic granulomas. Unlike necrobiosis lipoidica and granuloma annulare, where granulomas occur in association with other material, sarcoidosis has isolated granulomas. In some cases, these granulomas can penetrate the epidermis.
Another rare source of epidermal perforation is tumor cells. As previously mentioned, perforating pilomatricomas may fit into this category, along with melanocytes, with TE being reported in association with both nevi and melanoma. It is less clear what triggers these cells to leave the body via the epidermis. For example, whether they aberrantly express a migratory protein is a question left for speculation. Interestingly, pagetoid spread in a melanoma may reflect transepidermal elimination of melanoma cells and define a key characteristic of malignancy.
Gout is not typically included in itemized lists of causes for TE, but it has been rarely reported [4,5,6,7]. By using the categorical approach here, however, one can extrapolate that any granulomatous process could potentially be in the differential diagnosis. An organized categorical approach thus allows a broader differential to be considered.
In this case, the H&E histology was classic, and confirmatory testing was not required. If there were less material or less classic histology, the diagnosis could be confirmed using polarized light microscopy on a fresh smear or unstained section prepared with alcohol or Carnoy fixative. The crystals have negative birefringence, confirming that the material represents monosodium urate crystals. Performing a De Galantha stain, again using tissue fixed with alcohol or Carnoy fixative, is another method [7], but it is rarely used today.

3.2. Review of Recent Literature

We reviewed the literature over the past four years to provide an update on new developments in perforating dermatoses and TE. As discussed above, TE is not synonymous with ulceration, and perforation is sometimes applied loosely to cases of simple ulceration [8,9,10].
Most of the literature relates to primary perforating dermatosis. Two large series [11,12] confirm renal disease to be by far the most common cause of perforating dermatosis, followed by diabetes and malignancy. Many case reports and smaller series of acquired perforating dermatoses were identified [13,14,15,16,17,18,19,20,21,22,23,24,25], again most commonly associated with renal disease and/or diabetes [26,27,28,29,30,31,32,33,34,35,36]. Associations with other systemic diseases have also been observed. The most common disease was rheumatoid arthritis [37,38,39], but dermatomyositis [40] and lupus [41] were also reported.
Association with malignancy continues to be reported [42,43,44,45].
With the onset of immunotherapy and targeted therapy, several drugs have been implicated in reactive perforating dermatosis, including interferon [46], vemurafenib [47], erlotinib [48], and a PD-1 inhibitor [49]. Associations with immunobullous diseases have also been noted [50,51,52]. Less common associations include pregnancy [53,54], non-red tattoos [55], MRSA [56], copper deficiency [57], Down’s syndrome [58], and rhabdomyolysis-related hypercalcemia [59]. One report noted acquired perforating dermatosis in a pair of siblings [60], suggesting that there may be a genetic component involved in the etiology. Many reports focus on the treatment of perforating dermatoses [61,62,63,64,65,66,67,68,69,70,71,72,73], but this is beyond the scope of this report.
There has been much less discussion of secondary causes of TE. The most common reports are of granuloma annulare [74,75,76] and other granulomatous processes, including necrobiosis lipoidica [77,78], sarcoid [79], and elimination of suture material [80]. Other reports include perforating pseudoxanthoma elasticum [81,82,83], pilomatrixoma [84,85,86], sialolithiasis [87,88], lichen nitidus [89,90], and osteoma cutis [91]. Unusual reports of perforating cryocrystalglobulinemia in the context of multiple myeloma [92] and perforating ochronosis [93] again underscore the importance of a categorical approach over rigid adherence to previously published lists. While primary perforating dermatoses typically occur in older patients, several reports of secondary perforating processes have been noted in children [94,95,96].
Finally, several reports note that secondary perforating dermatoses can be mistaken for other entities, including squamous cell carcinoma [4], psoriasis [97,98], a nevus [99], and soft tissue malignancy [100,101]. Necrotizing infundibular crystalline folliculitis [102,103,104] can mimic perforating gout, having a cup-shaped surface (due to a distended follicular infundibulum) containing needle-like crystals.

4. Summary

Most of the recent literature reiterates known types of perforating dermatoses and known associations. Primary reactive dermatoses, including elastosis perforans serpiginosis, perforating collagenosis, perforating folliculitis, and Kyrle’s disease, are most commonly associated with renal insufficiency and diabetes. Less common associations include malignancy and systemic diseases such as rheumatoid arthritis. Immunotherapy and targeted cancer treatments have emerged as new causes of perforating dermatitis.
Our case of perforating gout represents a rare and unusual secondary perforating dermatosis. The diagnosis of perforating dermatoses can be diagnostically challenging, and diagnostic pitfalls include squamous cell carcinoma, psoriasis, and sarcoma.
Reliance on lists of causes of perforating dermatoses is sometimes inadequate, and a categorical approach is better able to accommodate rare causes of TE, such as gout. This case report also emphasizes the value of a generous biopsy. In our case, the gouty tophus is only present at a depth of 3 mm, which would be missed entirely by most shave biopsies.

Author Contributions

Conceptualization: S.H.B.; Methodology: S.H.B.; Formal Analysis: S.H.B. and M.B.; Investigation: S.H.B. and M.B.; Resources: S.H.B. and M.B.; Data Curation: S.H.B. and M.B.; Writing—original draft preparation: M.B.; Writing—review and editing: S.H.B. and M.B.; Visualization: S.H.B.; Supervision: S.H.B.; Project Administration: S.H.B. All authors have read and agreed to the published version of the manuscript.

Funding

This research received no external funding.

Institutional Review Board Statement

Not applicable.

Informed Consent Statement

Written informed consent has been obtained from the patient(s) to publish this paper.

Data Availability Statement

No additional data relating to this study is available.

Conflicts of Interest

The authors declare no conflict of interest.

Appendix A

Dermatopathology 10 00029 g0a1 550
Figure A1. Reactive perforating collagenosis. (A) Hematoxylin and eosin-stained skin at low magnification shows a cup-shaped depression with degenerating collagen extending from the ulcer base into the crust. (B) High magnification showing the TE of collagen fibers between keratinocytes at one edge of the ulcer (white arrows). (C) Masson’s trichrome confirms the presence of collagen fibers extruding between keratinocytes (black arrow). (D) Verhoeff elastic stain showing extrusion of elastic fragments between keratinocytes at one edge of the ulcer (white arrows).
Figure A1. Reactive perforating collagenosis. (A) Hematoxylin and eosin-stained skin at low magnification shows a cup-shaped depression with degenerating collagen extending from the ulcer base into the crust. (B) High magnification showing the TE of collagen fibers between keratinocytes at one edge of the ulcer (white arrows). (C) Masson’s trichrome confirms the presence of collagen fibers extruding between keratinocytes (black arrow). (D) Verhoeff elastic stain showing extrusion of elastic fragments between keratinocytes at one edge of the ulcer (white arrows).
Dermatopathology 10 00029 g0a1
Dermatopathology 10 00029 g0a2 550
Figure A2. Perforating granuloma annulare. Hematoxylin and eosin-stained skin at 100× magnification shows hyperkeratosis, interstitial histiocytes, and TE of pale eosinophilic amorphous material consistent with mucin (black arrow).
Figure A2. Perforating granuloma annulare. Hematoxylin and eosin-stained skin at 100× magnification shows hyperkeratosis, interstitial histiocytes, and TE of pale eosinophilic amorphous material consistent with mucin (black arrow).
Dermatopathology 10 00029 g0a2

References

  1. Woo, T.Y.; Rasmussen, J.E. Disorders of Transepidermal Elimination. Int. J. Dermatol. 1985, 24, 337–348. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  2. Ngan, V.; Tai, A. Peter MacCallum Sarah Smithson. (2022, April). Kyrle Disease. Available online: https://dermnetnz.org/topics/kyrle-disease (accessed on 20 May 2022).
  3. Rapini, R.P.; Hebert, A.A.; Drucker, C.R. Acquired perforating dermatosis: Evidence for combined transepidermal elimination of both collagen and elastic fibers. Arch. Dermatol. 1989, 125, 1074–1078. [Google Scholar] [CrossRef] [PubMed]
  4. Sutton, L.; Parekh, P. Perforating gout of the ear. Dermatol. Online J. 2016, 22, 13030. [Google Scholar] [CrossRef]
  5. Lucke, T.W.; Fallowfield, M.E.; Evans, A.; Lowe, J.G.; MacKie, R.M. Transepidermal elimination of urate-like crystals: A new perforating disorder? Br. J. Dermatol. 1999, 141, 310–314. [Google Scholar] [CrossRef]
  6. Park, J.; Kang, C.; Kim, S.; Park, J. A Case of Transepidermal Elimination in Gouty Tophus. Korean J. Dermatol. 1990, 28, 85–89. [Google Scholar]
  7. Cohen, P.R.; Schmidt, W.A.; Rapini, R.P. Chronic tophaceous gout with severely deforming arthritis: A case report with emphasis on histopathologic considerations. Cutis 1991, 48, 445–451. [Google Scholar]
  8. Gontijo, J.R.V.; Fernandes Júnior, F.; Pereira, L.B.; Pedrosa, M.S. Trauma-induced acquired reactive perforating collagenosis. An. Bras. Dermatol. 2021, 96, 392–393. [Google Scholar] [CrossRef]
  9. Quaade, A.S.; Zachariae, C.; Jørgensen, M.E.; Simonsen, A.B. Perforating Baker’s cyst mimicking cutaneous malignancy. JEADV Clin. Pract. 2022, 1, 436–437. [Google Scholar] [CrossRef]
  10. Gunawan, H.; Nursjamsi, N.C.D.; Achdiat, P.A.; Suwarsa, O. Reactive perforating leprosy: A rare case report of type 2 leprosy reaction. Int. J. Mycobacteriology 2020, 9, 451–453. [Google Scholar] [CrossRef]
  11. Garrido, P.M.; Queirós, C.; Borges-Costa, J.; Soares-Almeida, L.; Filipe, P. Acquired perforating dermatosis: Clinicopathologic study of a 10-year period at a tertiary teaching hospital. Int. J. Dermatol. 2020, 59, 445–450. [Google Scholar] [CrossRef]
  12. Gore Karaali, M.; Erdil, D.; Erdemir, V.A.; Gurel, M.S.; Koku Aksu, A.E.; Leblebici, C. Evaluation of clinicopathological and treatment characteristics of 80 patients with acquired perforating dermatosis. Dermatol. Ther. 2020, 33, e14465. [Google Scholar] [CrossRef]
  13. Zhang, H.; Chang, J.M. Reactive perforating collagenosis. Int. J. Dermatol. Venereol. 2019, 2, 62–64. [Google Scholar]
  14. Shah, H.; Tiwary, A.K.; Kumar, P. Transepidermal elimination: Historical evolution, pathogenesis and nosology. Indian J. Dermatol. Venereol. Leprol. 2018, 84, 753. [Google Scholar] [PubMed]
  15. Singhania, N.; Singhania, G.; Al-Rabadi, L. Acquired Reactive Perforating Collagenosis. Clin. Exp. Nephrol. 2020, 24, 1086–1087. [Google Scholar] [CrossRef]
  16. Wang, W.; Liao, Y.; Fu, L.; Kan, B.; Peng, X.; Lu, Y. Dermoscopy Features of Acquired Perforating Dermatosis Among 39 Patients. Front. Med. 2021, 8, 631642. [Google Scholar] [CrossRef] [PubMed]
  17. Sawant, S.; Gaikwad, N.; Hajirnis, K.; Vasani, R. Acquired perforating collagenosis: A clinico-pathological study of ten. Indian J. Pathol. Oncol. 2019, 6, 677–681. [Google Scholar] [CrossRef]
  18. Kochen, D.; Sohal, R.J.; Nat, A. Reactive Perforating Collagenosis; An Uncontrolled Pruritus That Left You Scratching Your Head. Cureus 2020, 12, e9175. [Google Scholar] [CrossRef]
  19. Catolico, G.A.I.C.; Ang-Tiu, C. Clinical and Histopathologic Features of Acquired Perforating Collagenosis: A Case Report. Acta Medica Philipp. 2020. [Google Scholar] [CrossRef]
  20. Elmas, Ö.F.; Kilitci, A.; Uyar, B. Dermoscopic patterns of acquired reactive perforating collagenosis. Dermatol. Pract. Concept. 2021, 11, e2020085. [Google Scholar] [CrossRef]
  21. Barit, J.V.J.G.; Lizarondo, F.P.J.; Cubillan, E.L.A. Clinicopathologic and Dermoscopic Features of Acquired Perforating Dermatosis: A Case Report. Acta Medica Philipp. 2019, 53. [Google Scholar] [CrossRef]
  22. Kollipara, H.; Satya, R.S.; Rao, G.R.; Attili, S.K. Acquired Reactive Perforating Collagenosis: Case Series. Indian Dermatol. Online J. 2023, 14, 72–76. [Google Scholar] [PubMed]
  23. Wang, C.; Liu, Y.H.; Wang, Y.X.; Zhang, J.Z.; Jin, J. Acquired reactive perforating collagenosis. Chin. Med. J. 2020, 133, 2119–2120. [Google Scholar] [CrossRef] [PubMed]
  24. Wilson, B.N.; Joseph, N.K.; Alhatem, A.; Karanfilian, K.M.; Behbahani, S.; Lambert, W.C. Dermatopathologic Signs of Systemic Disease I: Acquired Perforating Dermatosis and Kyrle Disease. Bettertogether 2020, 18, 301–303. [Google Scholar]
  25. Vaivadaitė, U.; Janonytė, U. A case report of acquired perforating dermatosis. In Proceedings of the Rīga Stradiņš University International Student Conference 2023 “Health and Social Sciences”(RSU-ISC), Riga, Latvia, 27–28 March 2023. [Google Scholar]
  26. Khan, A.A.; Javed, M.; Asif, M. Reactive Perforating Collagenosis; Dermatological Manifestation in a Patient with ESRD. Available online: https://pjmhsonline.com/2019/july_sep/pdf/713.pdf (accessed on 24 May 2023).
  27. Villela-Segura, U.; Miranda-Aguirre, A.I.; Estrada-Aguilar, L. Crateriform plaques in a patient with end-stage renal disease. The case of an acquired reactive perforating collagenosis. Nefrología (Engl. Ed.) 2020, 40, 358–360. [Google Scholar] [CrossRef]
  28. Akagun, T.; Oguz, I.D.; Usta, S.; Kabaday, H.O. Acquired Reactive Perforating Collagenosis in Patient with Diabetic Chronic Kidney Disease: A Case Report. Clin. Case Rep. Int. 2022, 6, 1312. [Google Scholar]
  29. Bejjanki, H.; Siroy, A.E.; Koratala, A. Reactive perforating collagenosis in end-stage renal disease: Not all that itches is uremic pruritis! Am. J. Med. 2019, 132, e658–e660. [Google Scholar] [CrossRef]
  30. Domingos, A.; Calças, R.; Carias, E.; Vidinha, J.; Guedes, A.M.; Santos, V.; Agostini, P.; Mendonça, F.I.; Neves, P.L. Acquired perforating dermatosis with associated complicated cellulitis and amputation in a hemodialysis patient. Clin. Nephrol. Case Stud. 2021, 9, 33. [Google Scholar] [CrossRef]
  31. Sari, A.R.P.; Puspitasari, M.; Soebono, H.; Trisnowati, N. Acquired Perforating Disorder: A Case with Multiple Underlying Diseases. Case Rep. Dermatol. 2022, 14, 107–111. [Google Scholar] [CrossRef]
  32. Khalidi, M.; Frikh, R.; Hjira, N.; Boui, M. Acquired perforating dermatosis in renal dialysis and diabetic patient: A case report. Our Dermatol Online 2021, 12, e40. [Google Scholar] [CrossRef]
  33. Zhang, X.; Yang, Y.; Shao, S. Acquired reactive perforating collagenosis: A case report and review of the literature. Medicine 2020, 99, e20391. [Google Scholar] [CrossRef]
  34. Özçelik, S.; Doğan, Y.; Kılıç, A.; Lebe, B. Giant variant of acquired perforating dermatosis in a patient with diabetes mellitus. TURKDERM-Turk. Arch. Dermatol. Venereol. 2020, 54, 25–28. [Google Scholar] [CrossRef]
  35. Razmi, T.M.; Chatterjee, D.; Parsad, D. Giant variant of acquired reactive perforating collagenosis in diabetic nephropathy. Postgrad. Med. J. 2019, 95, 52–53. [Google Scholar] [CrossRef]
  36. Ambalathinkal, J.J.; Phiske, M.M.; Someshwar, S.J. Acquired reactive perforating collagenosis, a rare entity at an uncommon site. Indian J. Pathol. Microbiol. 2022, 65, 895. [Google Scholar]
  37. Ladouce, F.; Beltzung, F.; Soubrier, M. Perforating dermatosis in rheumatoid arthritis. Rheumatology 2022, 61, 468. [Google Scholar] [CrossRef]
  38. Deb, S.; Srirangan, S. P38 A rare case of rheumatoid arthritis with perforating collagenosis. Rheumatology 2020, 59 (Suppl. 2), keaa111-037. [Google Scholar] [CrossRef]
  39. Ikeda, T.; Mikita, N.; Furukawa, F.; Iwahashi, Y. A case of rheumatoid vasculitis with acquired reactive perforating collagenosis. Mod. Rheumatol. 2019, 29, 547–550. [Google Scholar] [CrossRef]
  40. Gan, T.S.; Voo, S.Y.M. Acquired reactive perforating collagenosis—A rare cutaneous manifestation of anti-MDA5 dermatomyositis. Indian J. Dermatol. 2022, 67, 207. [Google Scholar]
  41. Alenzi, F. Reactive perforating collagenosis and systemic lupus erythematosus: A rare case report. Medicine 2022, 101, e32138. [Google Scholar] [CrossRef] [PubMed]
  42. Andrade, M.N.; Alfaro, M.F.; Van Caester, L.; Rossello, V.E.; Gallerano, V.; Herrero, M.; Pereyra, S.B. Dermatosis perforante adquirida, presentación de casos en pacientes con neoplasias malignas Acquired perforating dermatosis, a report of cases in patients with malignant neoplasms. Vol. 49 Supl. 1 Septiembre 2021, 49, 1–5. [Google Scholar]
  43. Cestari, S.; Dehó, I.Z.; Tovo, R.; Marques, G.; Lírio, I.D.; Macedo, M. Acquired perforating dermatosis in the setting of hepatocellular carcinoma. JAAD Case Rep. 2021, 18, 89–93. [Google Scholar]
  44. Huseynova, L.; Akdogan, N.; Gököz, Ö.; Evans, S.E. Acquired reactive perforating collagenosis in association with prostate adenocarcinoma, chronic lymphocytic leukemia, and Graves’ disease. An. Bras. Dermatol. 2020, 95, 336–339. [Google Scholar] [CrossRef] [PubMed]
  45. Malajian, D.; Husain, S.; Gallitano, S. Perforating Papules in a Patient With Acute Myeloid Leukemia. JAMA Dermatol. 2019, 155, 846–847. [Google Scholar] [CrossRef] [PubMed]
  46. Nicholls, I.; Wlodek, C.; Lamont, D. Interferon therapy causing perforating dermatosis. Clin. Exp. Dermatol. 2020, 45, 349–350. [Google Scholar] [CrossRef] [PubMed]
  47. Shiraishi, K.; Masunaga, T.; Tohyama, M.; Sayama, K. A case of perforating folliculitis induced by vemurafenib. Acta Derm.-Venereol. 2019, 99, 230–231. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  48. Jiang, X.; Song, T.T.; Hao, F. Erlotinib-induced reactive perforating collagenosis in a case of lung adenocarcinoma. Indian J. Dermatol. Venereol. Leprol. 2021, 87, 548–551. [Google Scholar] [CrossRef] [PubMed]
  49. Liu, X.; Wang, H.; Wan, Y.; Guo, Y.; Shan, S.J. Acquired Perforating Dermatosis Induced by PD-1 Inhibitor: A Case Report. Am. J. Dermatopathol. 2021, 43, 942–944. [Google Scholar] [CrossRef]
  50. Tan, Q.; Liu, L.; Zhang, J.; Ni, S.L. Acquired Reactive Perforating Collagenosis Associated with Linear Immunoglobulin A Bullous Disease. Acta Derm.-Venereol. 2020, 100, adv00268. [Google Scholar] [CrossRef]
  51. Schauer, F.; Kern, J.S.; Virtic, O.; Technau-Hafsi, K.; Meiss, F.; Thoma, K.; Athanasiou, I.; Sitaru, C.; Di Zenzo, G.; Izumi, K.; et al. A new clinical variant of acquired reactive perforating dermatosis-like bullous pemphigoid. Br. J. Dermatol. 2019, 180, 231–232. [Google Scholar] [CrossRef]
  52. Oka, M. Localized Bullous Pemphigoid in a Patient with Acquired Reactive Perforating Collagenosis. Case Rep. Dermatol. 2023, 15, 1–4. [Google Scholar] [CrossRef]
  53. Lo, Y.P.; Snehal, D.; Deng, L.H.; Chang, C.H.; Shih, C.J. Successful treatment of acquired reactive perforating collagenosis induced by pregnancy with allopurinol: A case report with review of literature. Dermatol. Sin. 2019, 37, 162. [Google Scholar]
  54. Lavery, M.J.; Winters, S.; Lorenzelli, D.; Low, S.E.; Sharma, N.; Ngan, K. Acquired reactive perforating collagenosis in association with pregnancy. Eur. J. Obstet. Gynecol. Reprod. Biol. 2020, 253, 339–341. [Google Scholar] [CrossRef] [PubMed]
  55. Grube, V.L.; Safeer, L.Z.; Hafeez, F. Acquired Reactive Perforating Collagenosis Occurring in Association With Nonred Ink Tattoo. Am. J. Dermatopathol. 2022, 44, 581–583. [Google Scholar] [CrossRef] [PubMed]
  56. Huang, F.; Ren, W.; Wang, M.; Li, X.; Pan, M. Acquired reactive perforating collagenosis combined with MRSA: A case report. Med. Int. 2023, 3, 1–4. [Google Scholar] [CrossRef] [PubMed]
  57. Varghese, J.A.; Quan, V.L.; Colavincenzo, M.L.; Zheng, L. Acquired perforating dermatosis in patients with copper deficiency. JAAD Case Rep. 2021, 15, 110–114. [Google Scholar] [CrossRef] [PubMed]
  58. Rajan, A.; Pai, V.V.; Shukla, P. Perforating folliculitis in Down’s syndrome—A rare case report. Egypt. J. Dermatol. Venerol. 2022, 42, 73. [Google Scholar] [CrossRef]
  59. Wang, F.Y.; Ng, C.Y.; Wu, J.; Kuo, K.L.; Chang, Y.Y.; Kuo, T.T. Acquired perforating calcific collagenosis in a drug addict with rhabdomyolysis and transient hypercalcemia. J. Cutan. Pathol. 2019, 46, 84–87. [Google Scholar] [CrossRef] [Green Version]
  60. Dheeraj, D.S.; Devi, B.G.; Gopal, K.V.T.; RAO, T.N. Reactive Perforating Collagenosis in Two Siblings—A Rare Case Presentation. IOSR J. Dent. Med. Sci. 2020, 19, 47–50. [Google Scholar]
  61. McMichael, J.; Stoff, B.K. Treatment of a perforating dermatosis with apremilast. JAAD Case Rep. 2021, 16, 155–157. [Google Scholar] [CrossRef]
  62. Kharghoria, G.; Grover, C. Treatment of acquired perforating dermatosis with colchicine. Indian Dermatol. Online J. 2022, 13, 131–132. [Google Scholar]
  63. Mattos, A.B.N.D.; Brummer, C.F.; Funchal, G.D.G.; Nunes, D.H. Perforating necrobiosis lipoidica: Good response to adalimumab. An. Bras. Dermatol. 2020, 94, 769–771. [Google Scholar] [CrossRef]
  64. Gao, L.; Gu, L.; Chen, Z.; Cao, S. Doxycycline combined with NB-UVB phototherapy for acquired reactive perforating collagenosis. Ther. Clin. Risk Manag. 2020, 16, 917–921. [Google Scholar] [CrossRef]
  65. Guo, L.; Zeng, Y.P.; Jin, H.Z. Reactive perforating collagenosis treated with dupilumab: A case report and literature review. Dermatol. Ther. 2022, 35, e15916. [Google Scholar] [CrossRef] [PubMed]
  66. Alsebayel, M.M.; Alzaid, T.; Alobaida, S.A. Dupilumab in acquired perforating dermatosis: A potential new treatment. JAAD Case Rep. 2022, 28, 34–36. [Google Scholar] [CrossRef]
  67. Izzat, M.B.; Kahila, A.; Izzat, A.W.; Zamlout, A.; Alashi, S. Uncharted surgical therapy for acquired perforating dermatoses. Asian Cardiovasc. Thorac. Ann. 2023, 31, 148–150. [Google Scholar] [CrossRef]
  68. Ye, B.; Cao, Y.; Liu, Y. Successful treatment of acquired reactive perforating collagenosis with itraconazole. Eur. J. Med. Res. 2021, 26, 74. [Google Scholar] [CrossRef] [PubMed]
  69. Wang, M.F.; Mei, X.L.; Wang, L.; Li, L.F. Clinical characteristics and prognosis of acquired perforating dermatosis: A case report. Exp. Ther. Med. 2020, 19, 3634–3640. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  70. Gil, F.; Cardoso, J.C.; Gil, J. Successful treatment of acquired perforating dermatosis with colchicine. Indian Dermatol. Online J. 2021, 12, 355. [Google Scholar] [CrossRef]
  71. Eljazouly, M.; Alj, M.; Chahboun, F.; Chahdi, H.; Chiheb, S.; Chahdi Sr, H. Acquired reactive perforating collagenosis: A case report. Cureus 2021, 13, e13583. [Google Scholar] [CrossRef]
  72. Gil-Lianes, J.; Riquelme-Mc Loughlin, C.; Mascaró, J.M., Jr. Reactive perforating collagenosis successfully treated with dupilumab. Australas. J. Dermatol. 2022, 63, 398. [Google Scholar] [CrossRef]
  73. Kawakami, T.; Akiyama, M.; Ishida-Yamamoto, A.; Nakano, H.; Mitoma, C.; Yoneda, K.; Suga, Y. Clinical practice guide for the treatment of perforating dermatosis. J. Dermatol. 2020, 47, 1374–1382. [Google Scholar] [CrossRef]
  74. Pap, N.; Bradamante, M.; Ljubojević-Hadžavdić, S. Localized perforating granuloma annulare. Acta Dermatovenerol. Croat. 2019, 27, 33. [Google Scholar]
  75. Deza, G.; Vidal, A.; Gallardo, F.; Iranzo, P.; de la Iglesia, L.C.; Pujol, R.M. Generalized Necrobiotic Palisading Granulomatous Follicular Eruption: A Peculiar Pustular Variant of Perforating Granuloma Annulare or an Individualized Disease? Am. J. Dermatopathol. 2020, 42, e22–e25. [Google Scholar] [CrossRef]
  76. Karadag, A.S.; Uzuncakmak, T.K.; Zemheri, E.I.; Arikan, E.E.; Ozkanli, S.; Akdeniz, N. Perforating Granuloma Annulare: A Case Report/Perforan Granuloma Annulare: Olgu Sunumu. Dermatoz 2020, 11, 21–24. [Google Scholar] [CrossRef]
  77. Maghfour, S.; El Abed, Y.H.; Gammoudi, R.; Boussofara, L.; Aouinallah, A.; Mokni, S.; Ghariani, N.; Belajouza, C.; Denguezli, M. Perforating necrobiosis lipoidica: A new case report. Endocr. Abstr. Biosci. 2019, 63, 886. [Google Scholar] [CrossRef]
  78. Gori, N.; Di Stefani, A.; De Luca, E.V.; Peris, K. A case of disseminated perforating necrobiosis lipoidica. Clin. Case Rep. 2020, 8, 808–810. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  79. Yamamoto, T.; Chen, K.R. Perforating plaque-type pretibial sarcoidosis with granulomatous phlebitis. Am. J. Dermatopathol. 2020, 42, 225–226. [Google Scholar] [CrossRef] [PubMed]
  80. Chaturvedi, H.T.; Chaturvedi, C.; Thammaiah, S.; Patel, V. Transepidermal elimination of suture material in lip biopsy specimen. J. Oral Maxillofac. Pathol. JOMFP 2022, 26, 392. [Google Scholar] [CrossRef]
  81. Bathina, M.; Hegde, S.P.; Shanavaz, A.A.; Saldanha, P.P. Pruritic periumbilical plaque as a presentation of a rare perforating dermatosis. Indian Dermatol. Online J. 2020, 11, 68. [Google Scholar] [PubMed]
  82. Mehta, P.; Rana, A. Periumbilical Perforating Pseudoxanthoma Elasticum/PPPXE—A Rare Case Report. J. Med. Sci. Clin. Res. 2021, 9. [Google Scholar] [CrossRef]
  83. Zhang, Y.; Feng, L.; Wang, M.; Wang, L. Perforating pseudoxanthoma elasticum of the arms: A rare case report. Eur. J. Dermatol. 2020, 30, 731–732. [Google Scholar]
  84. Watabe, D.; Mori, S.; Akasaka, T.; Motegi, S.I.; Ishikawa, O.; Amano, H. Six cases of perforating pilomatricoma: Anetodermic changes with expression of matrix metalloproteinases. J. Dermatol. 2020, 47, 82–85. [Google Scholar] [CrossRef] [PubMed]
  85. Iinuma, S.; Takahashi, C.; Hayashi, K.; Ishida-Yamamoto, A. Perforating pilomatricoma presenting as a cutaneous horn in a patient with myotonic dystrophy. Eur. J. Dermatol. 2022, 32, 284–285. [Google Scholar] [PubMed]
  86. Endo, M.; Yamamoto, T. A case of multiple perforating pilomatricomas. An. Bras. Dermatol. 2022, 97, 263–264. [Google Scholar] [CrossRef] [PubMed]
  87. Erdoğan, O. Sialolithiasis perforating the floor of mouth: A case report. Mucosa 2022, 5, 59–62. [Google Scholar] [CrossRef]
  88. Sikkerimath, S.; Anshu, A.; Jose, A. Perforating Sialolith: A Case Report. Asian J. Dent. Sci. 2020, 3, 12–15. [Google Scholar]
  89. LeWitt, T.; Quan, V.L.; Yazdan, P.; Zhou, X.A. Perforating lichen nitidus. JAAD Case Rep. 2021, 8, 4–8. [Google Scholar] [CrossRef]
  90. Li, X.Q.; Chen, X.; Li, B.; Du, J.; Hong, Y.S.; Zhang, J.Z.; Zhou, C. Dermoscopy of perforating lichen nitidus: A case report. Chin. Med. J. 2020, 133, 2135–2136. [Google Scholar] [CrossRef]
  91. Zipperer, K.; Munoz, A.; Kelly, E.; Goodwin, B. Acquired Perforating Osteoma Cutis: A Rare Histopathological Diagnosis. Am. J. Dermatopathol. 2022, 10, 1097. [Google Scholar] [CrossRef]
  92. Wee, C.L.P.; Lim, J.H.L.; Lee, J.S.S. Cryocrystalglobulinemia—An Uncommon Cutaneous Presentation of Multiple Myeloma and Novel Finding of Transepidermal Elimination of Crystals. Am. J. Dermatopathol. 2021, 43, e241–e244. [Google Scholar] [CrossRef]
  93. Jordaan, H.F. Transepidermal elimination in exogenous ochronosis: A report of two cases. Am. J. Dermatopathol. 1991, 13, 418–424. [Google Scholar] [CrossRef]
  94. Ziani, J.; Baybay, H.; Bennani, M.; Douhi, Z.; Elloudi, S.; Mernissi, F.Z. Perforating Granuloma Annulare in Children: A Case Report. Available online: https://www.oatext.com/perforating-granuloma-annulare-in-children-a-case-report.php#Article (accessed on 24 May 2023).
  95. Smith, C.; Hamilton, D.; Waterston, S. Rare case of multiple and perforating pilomatrixomas in a young girl with lymphovascular malformation reveals a potential new disease association. BMJ Case Rep. CP 2022, 15, e248076. [Google Scholar] [CrossRef] [PubMed]
  96. Aizman, L.; Gelman, A.; Marathe, K. A case of verrucous perforating collagenoma in a toddler. Pediatr. Dermatol. 2019, 36, 739–740. [Google Scholar] [CrossRef] [PubMed]
  97. Witkoff, B.M.; Ivanov, N.N.; Trotter, S.C. Perforating granuloma annulare appearing as a psoriasiform lesion. Case Rep. Dermatol. 2019, 11, 233. [Google Scholar] [CrossRef] [PubMed]
  98. Jacob, J.S.; Krenek, G.; Tschen, J. Perforating granuloma annulare mimicking psoriasis. Cureus 2020, 12, e9983. [Google Scholar] [CrossRef]
  99. Seo, B.H.; Kim, J.H.; Oh, Y.W.; Kim, D.H.; Suh, H.S.; Choi, Y.S. P338: A case of perforating pilomatricoma mimicking intradermal nevus on the scalp. 프로그램북 (구 초록집) 2019, 71, 485–486. [Google Scholar]
  100. De Silva, L.; Lokuhetty, M.S. Giant variant of acquired perforating dermatosis, clinically masquerading as a sarcoma: A report of a rare case. Indian J. Pathol. Microbiol. 2020, 63, 128. [Google Scholar] [CrossRef]
  101. Ornetti, P.; Guillier, D.; Jeudy, G. Perforating Rheumatoid Nodule Mimicking Malignant Soft-tissue Mass of the Forearm. J. Rheumatol. 2021, 48, 1103. [Google Scholar] [CrossRef]
  102. Kossard, S. Eruptive necrotizing infundibular crystalline folliculitis: An expression of an abortive sebaceous follicular repair pathway linked to committed infundibular stem cells? Am. J. Dermatopathol. 2021, 43, 867. [Google Scholar] [CrossRef]
  103. Wiedemeyer, K.; Brenn, T.; Naert, K. Necrotizing Infundibular Crystalline Folliculitis—A Case Report of a Rare Entity and Review of the Literature. Am. J. Dermatopathol. 2022, 10, 1097. [Google Scholar] [CrossRef]
  104. Fischer, A.S.; Pei, S.; Shields, B.E.; Rosenbach, M.; Rubin, A.I. Dermatomal necrotizing infundibular crystalline folliculitis following herpes zoster in a patient on PD-1 inhibitor therapy. J. Cutan. Pathol. 2020, 47, 501–505. [Google Scholar] [CrossRef]
Dermatopathology 10 00029 g001 550
Figure 1. (a) Hematoxylin and eosin-stained skin at low magnification shows pseudoepitheliomatous hyperplasia and degenerating material abutting the epidermal downgrowth. (b) At high power, fluffy amphiphilic material surrounded by a palisade of histiocytes is visible.
Figure 1. (a) Hematoxylin and eosin-stained skin at low magnification shows pseudoepitheliomatous hyperplasia and degenerating material abutting the epidermal downgrowth. (b) At high power, fluffy amphiphilic material surrounded by a palisade of histiocytes is visible.
Dermatopathology 10 00029 g001
Table
Table 1. Categorization of perforating disorders based on the source of the TE material.
Table 1. Categorization of perforating disorders based on the source of the TE material.
Primary
SourceDiseaseTE Material
Endogenous materialElastosis perforans serpiginosaElastin
Reactive perforating collagenosisCollagen
Kyrle’s diseaseKeratin and other material
Perforating folliculitisElastin and/or Collagen
Acquired perforating dermatosisUmbrella term for the entities listed above
Secondary
SourceDiseaseTE Material
Abnormal endogenous materialChondrodermatitis nodularis helicisDegraded cartilage
Perforating pseudoxanthoma elasticumAbnormal elastin
Perforating osteoma cutisEctopic bone
Perforating calcinosis cutisEctopic calcium
Perforating calcific collagenosisCalcified collagen
Perforating calcific elastosisCalcified elastin
DepositsPerforating mucinosisMucin
Perforating amyloidosisAmyloid
Perforating cryocrystalglobulinemiaCryocrystalglobulins
Infection with depositsBotryomycosisExtra-bacterial granule
GranulomasPerforating granuloma annulareNecrobiotic granulomas with mucin
Perforating necrobiosis lipoidicanecrobiotic granulomas
Perforating sarcoidosisSarcoidal granulomas
Perforating rheumatoid noduleGranuloma, fibrinoid
Perforating foreign bodyForeign body granulomas and foreign material
Perforating tattoo reactionGranulomatous inflammation with tattoo pigment
Perforating ochronosisGranulomatous inflammation with homogentisic acid
Perforating goutGranulomatous inflammation with monosodium urate
Granulomatous InfectionsSchistosomiasisGranulomatous inflammation
ChromomycosisGranulomatous inflammation
TuberculosisGranulomas
LeprosyGranulomas
LeishmaniasisGranulomatous inflammation
HistoplasmosisGranulomatous inflammation
OtherLichen nitidusInflammatory cells
MelanomaMelanocytes
NevusMelanocytes
Pilomatricomaabnormal immature keratinocytes
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Bohdanowicz, M.; Bradshaw, S.H. Perforating Gout: Expanding the Differential for Transepidermal Elimination. Dermatopathology 2023, 10, 207-218. https://doi.org/10.3390/dermatopathology10030029

AMA Style

Bohdanowicz M, Bradshaw SH. Perforating Gout: Expanding the Differential for Transepidermal Elimination. Dermatopathology. 2023; 10(3):207-218. https://doi.org/10.3390/dermatopathology10030029

Chicago/Turabian Style

Bohdanowicz, Michal, and Scott H. Bradshaw. 2023. "Perforating Gout: Expanding the Differential for Transepidermal Elimination" Dermatopathology 10, no. 3: 207-218. https://doi.org/10.3390/dermatopathology10030029

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