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Vol. 110. Núm. 7.
Páginas 613-615 (Septiembre 2019)
Vol. 110. Núm. 7.
Páginas 613-615 (Septiembre 2019)
Case and Research Letters
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Reverse Isotopic Phenomenon in Drug Reaction with Eosinophilia and Systemic Symptoms
Fenómeno isotópico inverso en el síndrome de reacción por drogas con eosinofilia y síntomas sistémicos
M. Adil
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, Syed Suhail Amin, R. Dinesh Raj, Hera Tabassum
Departamento de Dermatología, Jawaharlal Nehru Medical College, Aligarh Muslim University, Aligarh, India
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Table 1. Details of cases of isotopic non-response reported in literature.
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Reverse isotopic phenomenon, or isotopic non-response, is an extremely rare phenomenon characterised by the absence of a skin disease at the site of another unrelated skin disease which is already healed.1 Sparing occurs at the healed site of an inflammatory disease. Most reports of reverse isotopic phenomenon show the sparing of the skin previously involved in herpes zoster.2

We describe a case of Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) syndrome due to carbamazepine with isotopic non-response at the site of healed herpes zoster.

A 60 year male presented to us with complaints of fever, breathlessness and red itchy rash over body since 7 days. The patient had developed herpes zoster on the lower part of the right chest around two months back, and was prescribed Tab Carbamazepine by a local physician for the residual pain.

On examination, the patient was found to have generalised swelling, particularly prominent over the periocular areas. He was febrile (100.6 F) and had tachycardia (heart rate-110/min) and tachypnea (respiratory rate-22/min). The abdomen was distended and bowels sounds were not heard. There was mildly tender lymphadenopathy in inguinal and axillary areas. Cutaneous examination revealed erythematous maculopapular lesions predominantly distributed over the face, trunk and proximal extremities with tendency to coalesce such that the whole of the trunk was involved except the right T9 dermatome which was characteristically spared. [Fig. 1] The skin of the right T9 dermatome showed hyperpigmented scars of the healed herpes zoster. [Fig. 2] The rest of the cutaneous and systemic examination was normal.

Figure 1.

Confluent erythematous maculopapular lesions over the chest and abdomen with sparing of the right T9 dermatome.

Figure 2.

A closer view of the spared site shows hyperpigmentation and scars of healed herpes zoster with sparing of the T9 dermatome by the rash.


Investigations revealed leucocytosis (TLC- 15500/ cu mm; normal- 4000-11000/ cu mm) with eosinophilia (AEC- 1580/ cu mm; normal- 40-440/ cu mm). There was elevation of liver enzymes (SGOT- 660 IU; normal- 7-40 IU, SGPT- 590 IU; normal- 7-56 IU) and increased blood urea (120mg/dl; normal- 10-40mg/dl) and serum creatinine (1.9mg/dl; normal- 0.3-1.2mg/dl). The patient had a normal chest radiograph and a gas filled distended bowel suggestive of paralytic ileus. The patient had hyperamylesemia (260 U/l; normal- 40-140 U/l) suggestive of pancreatitis. He subsequently developed fatal acute respiratory distress syndrome. A diagnosis of DRESS syndrome was made based on the RegiSCAR criteria.3

DRESS syndrome is a rare idiosyncratic reaction reaction to a drug characterised by skin rash, fever, lymphadenopathy, eosinophilia and multiorgan involvement. It is commonly caused by anticonvulsant medications, allopurinol, minocycline and antiretroviral agents like abacavir. Pathogenesis is unclear but it is believed to occur in patients who metabolise the drugs and its active metabolites slowly. A genetic predisposition exists and Human Herpesviruses has been associated. The cross reaction of antiviral T cells with the culprit drug has been proposed to mediate this syndrome.4 However, the sparing of the healed herpes zoster site casts doubt regarding this theory.

The possible reason for the sparing of a skin lesion to a secondary insult is unclear. The rash of DRESS may result from alteration of the local immune response by a virus itself or by production of Th1 cytokines like TNF-alpha, IFN-gamma, IL-2 and IL-5.2 The loss or hypoactivity of Langerhans cells at the site of herpes zoster has been demonstrated and may play a role in this sparing phenomenon.5 Also, herpesvirus infected keratinocytes have decreased expression of MHC and ICAM-1, hindering their function as antigen presenting cells and inhibiting T cell response, thereby leading to the skin rash of DRESS.6

Isotopic non-response needs to be differentiated from isomorphic non-response or Renbök phenomenon. The site of another unrelated skin disease is spared in both of the above phenomenon. This disease is still active in Renbök phenomenon while it is healed in the isotopic non-response.1

Very few cases of reverse isotopic phenomenon have been reported in literature. There reports have shown the sparing of the sites of vaccination,7 herpes zoster2,5,6,8,9 and burn scar10 that have occurred in diverse conditions like epidermal necrolysis,2 erythema multiformae,8 cutaneous lymphomas,5 leprosy9 and annular elastolytic giant cell granuloma.10 [Table 1] Ours is probably the first case of reverse isotopic phenomenon in DRESS syndrome.

Table 1.

Details of cases of isotopic non-response reported in literature.

N.° de caso  Estudio  Edad/sexo  Enfermedad secundaria  Sitio de la preservación  Enfermedad primaria 
Nuestro caso  60 años/varón  Síndrome DRESS  Tronco (dermatoma T9 derecho)  Herpes zóster 
Tenea D2 (2010)  39 años/mujer  Síndrome Stevens-Johnson  Lado derecho del tronco  Herpes zóster 
Kannangara AP et al.6 (2008)  53 años/mujer  Síndrome sobreposición SJS-TEN  Nervio craneal V1 izquierda  Herpes zóster 
Kannangara AP et al.6 (2008)  62 años/varón  Eritrodermia  C3-C4 izquierda  Herpes zóster 
Park H et al.7 (2008)  67 años/mujer  Eritema multiforme  Tronco (dermatoma T3)  Herpes zóster 
Twersky JM et al.5 (2004)  58 años/varón  Linfoma cutáneo células T  Tronco (dermatoma T8 izquierdo)  Herpes zóster 
Jain R et al.8 (2003)  ND  Lepra «borderline»  ND  Herpes zóster 
Jain R et al.8 (2003)  ND  Lepra «borderline»  ND  Herpes zóster 
Okaya-Bayazit E et al.9 (1999)  72 años/mujer  Granuloma elastolítico anular de células gigantes  Antebrazo izquierdo  Cicatriz quemadura 
10  Nasca MR et al.10 (1995)  53 años/varón  Acné esteroideo  Espalda  Sitio irradiación Rx 
11  Huilgol SC et al.11 (1995)  74 años/varón  Granuloma anulargeneralizado  Brazo izquierdo  Punto de vacunación 

DRESS: drug reaction with eosinophilia and systemic symptoms; ND: no disponible; Rx: rayos X; SJS-TEN: Stevens-Johnson syndrome-toxic epidermal necrolysis.

Conflicts of Interest

The authors declare that they have no conflicts of interest.

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Please cite this article as: Adil M, Amin SS, Dinesh Raj R, Tabassum H. Reverse Isotopic Phenomenon in Drug Reaction with Eosinophilia and Systemic Symptoms. Actas Dermosifiliogr. 2019;110:613–615.

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