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 Table of Contents  
Year : 2017  |  Volume : 1  |  Issue : 2  |  Page : 78-81

Immunosuppressed cutaneous District: The finale of the fascinating farrago of confounding responses?

Department of Dermatology, Hassan Institute of Medical Sciences, Hassan, Karnataka, India

Date of Web Publication28-Jul-2017

Correspondence Address:
B C Ravikumar
Department of Dermatology, Hassan Institute of Medical Sciences, Hassan - 573 201, Karnataka
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/CDR.CDR_18_17

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How to cite this article:
Raghukumar S, Ravikumar B C. Immunosuppressed cutaneous District: The finale of the fascinating farrago of confounding responses?. Clin Dermatol Rev 2017;1:78-81

How to cite this URL:
Raghukumar S, Ravikumar B C. Immunosuppressed cutaneous District: The finale of the fascinating farrago of confounding responses?. Clin Dermatol Rev [serial online] 2017 [cited 2023 Jan 29];1:78-81. Available from: https://www.cdriadvlkn.org/text.asp?2017/1/2/78/211779

  Introduction Top

The word “district” literally means an area or territory that is characterized by a particular feature or activity. The immunocompromised cutaneous district (ICD) is a conceptual entity, consolidating apparently different clinical conditions under an umbrella term.[1],[2],[3],[4] It basically represents a vulnerable location for the onset of opportunistic infections, tumors, and dysimmune reactions either confined to that site or selectively sparing the site.[3] The events that are capable of rendering a skin region as a potential ICD are many and maybe in the form of herpetic infections, trauma of various kinds, ionizing or ultraviolet (UV) radiations, burns, chronic lymph stasis, tattooing, intradermal vaccinations, and other causes of disparate nature.[2],[3]

It represents a sectorial immune destabilization which not limited by anatomical boundaries and can occur in immunocompetent individuals as well.[4] In general, the immunologic behavior of an ICD is different from that of the rest of the body and the precise pathomechanisms of each is yet to be elucidated. Proposed theories include damage to the sensory nerve fibers that release immunity-related peptides or dysfunction of the lymphatic drainage that hinders the normal trafficking of immunocompetent cells or both. As a result of which, the ICD can be either defective (which favors the outbreak of opportunistic infections or tumors) or overactive (which favors the outbreak of immune disorders).[1],[3]

The ICD is essentially of either of the two types:

  1. “Locus minoris resistentiae” - Derived from Latin term meaning place of lesser resistance and is defined as a site of the body that offers lesser resistance or increased vulnerability than the rest of the body to the onset of disease [2],[3]
  2. “Locus maioris resistentiae” - Defined as a site of the body that offers greater resistance than the rest of the body to the onset of disease.[2],[3]

The various responses occurring in an ICD have been categorized in [Table 1] and further illustrated as follows.[1],[4],[5]
Table 1: Categories of several responses occurring in an immunosuppressed cutaneous dist

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These responses are further elaborated with a few examples as follows:

  Koebner Phenomenon/isomorphic Response Top

The development of isomorphic or identical lesions in the traumatized uninvolved skin of patients who have cutaneous diseases. The new lesions are clinically and histopathologically similar to those in the diseased skin.

Boyd and Neldner classification of Koebner phenomenon

  1. True isomorphic phenomenon: The characteristic features of the isomorphic phenomenon is displayed by three diseases-psoriasis, lichen planus, and vitiligo
  2. Pseudoisomorphic phenomenon: Occurs due to autoinoculation in infectious diseases such as warts and molluscum contagiosum
  3. Occasionally occurring isomorphic phenomenon: Some diseases occasionally localize to sites of trauma, for example, cancer (gastric, testicular or mammary), Darier's disease, erythema multiforme, Hailey–Hailey disease, Kaposi's sarcoma, Kyrle's disease, lichen sclerosus et atrophicus, pellagra, perforating folliculitis, and reactive perforating collagenosis
  4. Questionable isomorphic phenomenon: These are conditions that have been associated with the Koebner phenomenon, but the evidence is minimal in the form of case reports. For example, anaphylactoid purpura, bullous pemphigoid, dermatitis herpetiformis, discoid lupus erythematosus, eczema, erythrokeratoderma variabilis, keratoacanthoma, lichen amyloidosis, lichen nitidus, multicentric reticulohistiocytosis, nevocytic nevi, pityriasis rubra pilaris, porokeratosis of Mibelli, urticaria pigmentosa, transient acantholyic dermatosis, vasculitis, and xanthoma eruptivum.[6],[7]

Note – The Koebner's phenomenon must be differentiated from “pathergy phenomenon.” Although both generate lesions in areas of trauma, the difference between Koebner phenomenon and pathergy is that, in the former, the lesions are clinically and histopathologically identical to the previous disease, while in the latter, there is a nonspecific reaction with the formation of papules or pustules, without the formation of lesion of an underlying disease and histopathologically revealing monocytic infiltrate with perivascular and periadnexal increase in mast cells.[8],[9]

Reverse Koebner response/isomorphic nonresponse

The nonappearance or disappearance of the lesions of particular dermatoses at the site of injury. Classically described in psoriasis and can also be followed by trauma due to electrodessication, sandpaper abrasion, surgery, and infections like rubeola or acute tonsillitis.[6]

Remote reverse Koebner phenomenon

Spontaneous repigmentation of the vitiligo patches distant from those treated by autologous punch grafts.[6] It is hypothesized that fresh cytokines from the donor skin may stimulate the melanocytes at the distant sites after local absorption.[6]

Inverse Koebner phenomenon/Renbok phenomenon

Vanishing of a dermatosis after the onset of a new disease at the same location.[1],[6] Described in alopecia areata and universalis where re-epilation is seen after the appearance of psoriasiform plaques at the same site.[10]

Deep Koebner phenomenon

Traumatic injury or physical stress triggers the subsequent development of psoriatic arthritis.[5]

Wolf's postherpetic isotopic response/nonresponse

The emergence/sparing of a new skin disease exactly in the same place of a previously healed herpetic scar.[1],[5],[6]

Wolf's postherpetic isotopic R: Occurrence of infections, tumors or dysimmune reactions on healed zoster-affected dermatomes.

Wolf's postherpetic isotopic nonresponse (NR): Cutaneous T-cell lymphoma sparing dermatomes previously involved by herpes zoster.[11]

Note – The differences between Koebner phenomenon and Wolf phenomenon is that the Koebner phenomenon describes lesions that are morphologically similar to an existing disease in the area of trauma whereas, in Wolf phenomenon, a new disease appears in the same area of the scar.

Isomosaictopic response/nonresponse

A new dermatoses occurring/sparing an area of cutaneous mosaicism.

Isomosaictopic R: Eczema confined to Becker's nevus.[12]

Isomosaictopic NR: Port wine stain in Sturge–Weber syndrome spared from facial allergic contact dermatitis.[13]

Isoradiotopic response/nonresponse

A secondary dermatosis arising/sparing an area of ionizing radiation field, conventional electron beam radiotherapy, and UV radiation.[4],[5]

Isoradiotopic R: Pemphigus presenting in a radiotherapy portal for breast cancer.[14]

Isoradiotopic NR: Ampicillin-induced drug reaction sparing the site of the radiation portal.[15]

Isophototopic response/nonresponse

The occurrence of a secondary dermatoses in skin exposed to a natural (sun)/artificial (UV lamps) source of UV radiation or a localized cutaneous photoanergy sparing the region.[4]

Isophototopic R: Photolocalized varicella.[16]

Isophototopic NR: Mycosis fungoides limited to skin covered by a swimming suit and sparing photoexposed areas.[17]

Isocaumatopic response/nonresponse

The occurrence/sparing of an eruption at the site of an ancient burn scar.[1],[4]

Isocaumatopic R: Monolesional bullous pemphigoid selectively appearing on burn scar.[1]

Isocaumatopic NR: Annular elastolytic giant cell granuloma sparing a burn scar.[18]

Isotraumatopic response/nonresponse

The occurrence/sparing of a cutaneous eruption on a traumatized area.[1],[4]

Isotraumatopic R: Posttraumatic discoid lupus erythematosus.[19]

Isotraumatopic NR: Psoriasis sparing the site of pressure application.

Isovaccinetopic response/nonresponse

The occurrence/sparing of a cutaneous eruption at the site of previous vaccination.[1],[5]

Isovaccinetopic R: Tuberculosis and cancer on a BCG vaccination site.[20]

Isovaccinetopic NR: Generalized granuloma annulare sparing vaccination sites.[21]

Isotattootopic response/nonresponse

The occurrence/sparing of a cutaneous eruption at the site of a tattoo.[1],[4],[5]

Isotattootopic R: Wart on the areas of black dye within a tattoo.[22]

Isotattootopic NR: Purpuric rash sparing tattooed skin.[23]

Isoneuraltopic response/nonresponse

The occurrence/sparing of a cutaneous eruption at the site of neurological deficit.[1],[5]

Isoneuraltopic R: Papillomatosis cutis arising on paraplegic lower limb.[24]

Isoneuraltopic NR: Psoriasis sparing postpolio affected limb.[25]

Isolymphostatic response/nonresponse

A secondary dermatoses occurring in an area of chronic lymph stasis or secondary lymphedema.[1]

Isolymphostatic R: Stewart–Treves syndrome.[26]

Isolymphostatic NR: Bullous pemphigoid sparing lymphedema.[27]

Note – The above events has to be distinguished from the “anatopic phenomenon” wherein two diseases are present simultaneously and not one disease healed at the presentation of the other. It occurs due to the modulation of the inflammatory response of one dermatosis by another unrelated cutaneous infection at the same site. For instance, sparing of leprosy patches by ampicillin hypersensitivity rash and dapsone hypersensitivity syndrome.[28],[29] Viral exanthem, acute generalized exanthematous pustulosis, and polymorphous light eruption sparing sites affected with tinea versicolor.[30],[31]

ICD is an evolving concept which is proposed with the intention of a better understanding of some of the diseases where immunological mechanisms play a major role especially in cases where the immunological mechanisms gets altered at skin areas which is subjected to external insults. It is of paramount importance for both diagnostic and preventive purposes. The knowledge that a previously injured or diseased cutaneous site may in time harbor secondary skin disorders, different from the first one, can provide diagnostic aid in some circumstances. Awareness that an injured or diseased skin site may be vulnerable site for an entire lifespan should alert both the physician and the patient alike to keep the site under special surveillance. Any new lesion appearing on that site should promptly be investigated by all means and when necessary, immediately treated (infections, dysimmune reactions) or removed (neoformations, tumors).

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Conflicts of interest

There are no conflicts of interest.

  References Top

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Caccavale S, Di Mattia D, Ruocco E. Loco-regional immune default: The immunocompromised district in human and comparative dermatology. Clin Dermatol 2016;34:654-7.  Back to cited text no. 2
Ruocco V, Ruocco E, Piccolo V, Brunetti G, Guerrera LP, Wolf R. The immunocompromised district in dermatology: A unifying pathogenic view of the regional immune dysregulation. Clin Dermatol 2014;32:569-76.  Back to cited text no. 3
Piccolo V, Baroni A, Russo T, Schwartz RA. Ruocco's immunocompromised cutaneous district. Int J Dermatol 2016;55:135-41.  Back to cited text no. 4
Kannangara AP, Yosipovitch G, Fleischer AB Jr. Proposed classification for Koebner, Wolf isotopic, Renbok, Koebner nonreaction, isotopic nonreaction and other related phenomen. Dermatol Online J 2014;20. pii: 13030/qt96s656b4.  Back to cited text no. 5
Camargo CM, Brotas AM, Ramos-e-Silva M, Carneiro S. Isomorphic phenomenon of Koebner: Facts and controversies. Clin Dermatol 2013;31:741-9.  Back to cited text no. 6
Boyd AS, Neldner KH. The isomorphic response of Koebner. Int J Dermatol 1990;29:401-10.  Back to cited text no. 7
Baker MR, Smith EV, Seidi OA. Pathergy test. Pract Neurol 2011;11:301-2.  Back to cited text no. 8
Varol A, Seifert O, Anderson CD. The skin pathergy test: Innately useful? Arch Dermatol Res 2010;302:155-68.  Back to cited text no. 9
Criado PR, Valente NY, Michalany NS, Martins JE, Romiti R, Aoki V, et al. An unusual association between scalp psoriasis and ophiasic alopecia areata: The Renbök phenomenon. Clin Exp Dermatol 2007;32:320-1.  Back to cited text no. 10
Twersky JM, Nordlund JJ. Cutaneous T-cell lymphoma sparing resolving dermatomal herpes zoster lesions: An unusual phenomenon and implications for pathophysiology. J Am Acad Dermatol 2004;51:123-6.  Back to cited text no. 11
Lee DJ, Kang HY. Eczema confined to Becker's nevus on the face: The behavior of melanocytes during inflammation. Ann Dermatol 2012;24:99-100.  Back to cited text no. 12
Al-Rohil RN, Leung D, Carlson JA. Congenital vulnerability of cutaneous segments arising from skin mosaicism: A genetic basis for locus minoris resistentiae. Clin Dermatol 2014;32:577-91.  Back to cited text no. 13
Ruocco E, Lo Schiavo A, Caccavale S. Pemphigus induced by radiotherapy for breast cancer: An instance of immunocompromised district. Eur J Dermatol 2014;24:278-9.  Back to cited text no. 14
Bernhard JD, Haynes HA. Nonrashes. Part I: The Koebner nonreaction. Cutis 1982;29:158-64.  Back to cited text no. 15
Boyd AS, Neldner KH, Zemtsov A, Shihada B. Photolocalized varicella. J Am Acad Dermatol 1992;26(5 Pt 1):772-4.  Back to cited text no. 16
Grilli R, Soriano L, Fariña C, Martin L, Requena L. Cutaneous eruption limited to skin covered by a swimming suit: Mycosis fungoides. Arch Dermatol 2002;138:527-32.  Back to cited text no. 17
Ozkaya-Bayazit E, Büyükbabani N, Baykal C, Oztürk A, Okçu M, Soyer HP. Annular elastolytic giant cell granuloma: Sparing of a burn scar and successful treatment with chloroquine. Br J Dermatol 1999;140:525-30.  Back to cited text no. 18
Ruocco E, Brunetti G, Sangiuliano S, Caccavale S, Lo Schiavo A. Discoid lupus erythematosus at a site of previous injury. Australas J Dermatol 2013;54:e16-8.  Back to cited text no. 19
Lo Schiavo A, Brasiello M, Sangiuliano S, Ruocco E. Tuberculosis and cancer on a BCG vaccination site: An instance of immunocompromised district. Int J Dermatol 2014;53:e28-9.  Back to cited text no. 20
Huilgol SC, Liddell K, Black MM. Generalized granuloma annulare sparing vaccination sites. Clin Exp Dermatol 1995;20:51-3.  Back to cited text no. 21
Miller DM, Brodell RT. Verruca restricted to the areas of black dye within a tattoo. Arch Dermatol 1994;130:1453-4.  Back to cited text no. 22
Pinal-Fernandez I, Solans-Laqué R. The 'sparing phenomenon' of purpuric rash over tattooed skin. Dermatology 2014;228:27-30.  Back to cited text no. 23
Baroni A, Ruocco V, Di Maio R, Nuzzo T, Del Vecchio M, Ruocco E. Papillomatosis cutis arising on an immuno-compromised district due to paraplegia. Br J Dermatol 2010;163:646-8.  Back to cited text no. 24
Ravikumar B, Sinhasan. Psoriasis sparing the polio-affected limb: Is it merely the koebner phenomenon? Indian J Dermatol 2014;59:505-6.  Back to cited text no. 25
[PUBMED]  [Full text]  
Sharma A, Schwartz RA. Stewart-Treves syndrome: Pathogenesis and management. J Am Acad Dermatol 2012;67:1342-8.  Back to cited text no. 26
Roguedas AM, Crespel E, Kupfer I, De Saint Martin L, Misery L, Sassolas B. Bullous pemphigoid sparing acquired lymphedema. Ann Dermatol Venereol 2003;130:141-2.  Back to cited text no. 27
Pavithran K. Sparing of leprosy macule in ampicillin hypersensitivity rash. Indian J Lepr 1987;59:309-12.  Back to cited text no. 28
Ng PP, Goh CL. Sparing of tuberculoid leprosy patch in a patient with dapsone hypersensitivity syndrome. J Am Acad Dermatol 1998;39(4 Pt 1):646-8.  Back to cited text no. 29
Pakran J, Riyaz N. Interesting effect of Malassezia spp. infection on dermatoses of other origins. Int J Dermatol 2011;50:1518-21.  Back to cited text no. 30
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