infections are common in patients with systemic lupus erythematosus ( sle ) throughout the course of their disease and remain a source of morbidity and mortality [ 1 , 2 , 4 ] . apart from the host genetic predisposition which may determine the general susceptibility to both infections ( i.e. herpes zoster ) and sle , a defective cell - mediated immunity , a hyperactive humoral immunity associated with polyclonal b - cell activation and the adverse effects of immunosuppressive treatment have been demonstrated by immunological studies [ 1 , 2 , 6 ] . well - documented cases of stevens - johnson syndrome ( sjs ) and toxic epidermal necrolysis occurring at the site of resolved herpes zoster ( isotopic response ) have been reported since the first recognition of this dermatological phenomenon by wolf et al . [ 3 , 4 ] in 1985 . however , a dermatosis sparing another unrelated and already healed skin disease ( reverse isotopic response ) is a rarely encountered phenomenon . a 39-year - old indian woman with sle diagnosed in 2003 developed right thoracoabdominal herpes zoster in december 2007 . the vesicular eruption was preceded by a prodrome of dermatomal pain and constitutional symptoms lasting for about 4 days . the patient was treated appropriately with acyclovir for 7 days and the herpes zoster resolved uneventfully . however , a burning sensation persisted in the affected area and carbamazepine ( cbz ) was started for postherpetic neuralgia 3 weeks following the clearance of the lesions . eleven days later , the patient developed painful erosions of the oral mucosa , conjunctival hyperemia , purpuric macules and patches , and flaccid blisters . the striking feature of this new eruption was the distinct sparing of the area previously affected by the herpes zoster ( fig . serum and lesional skin tissue samples were collected at the time of presentation and a complete blood count with differential analysis was normal . acute phase proteins , liver enzymes , urea / electrolytes / creatinine levels , thyroid functional tests , rheumatoid factor and urinalysis were within normal limits . an antinuclear antibody titer as well as antibodies to ds - dna , anti - ro , and anti - la histopathological examination of the lesional skin showed features in keeping with sjs ( epidermal necrosis , marked dermal edema and sparse perivascular lymphocytic infiltrate ; fig . 2 ) . chest x - ray and ecg revealed no abnormalities , and the ppd test was negative . the patient 's medical history was relevant for bronchial asthma with many recurrent infectious episodes in the past . taking into consideration her asian ancestry and under the impression of cbz - induced sjs , we attempted to perform genotyping , but the patient declined the test due to the cost involvement . the offending drug was withdrawn and oral prednisone was increased from the maintenance dose of 10 mg / day she was receiving for her sle during the past 3 years to 1 mg / body weight / day . the patient remained clinically stable during the subsequent 4 months although she had a flare - up of sle in may 2008 , which was well controlled with immunosuppressive therapy . the patient was admitted with respiratory distress , pneumonia / pleuritis , and active sle . based on the clinical presentation and the pathology report , a diagnosis of cbz - induced sjs with a reverse isotopic phenomenon was established in a patient with sle . in agreement with other authors reports , it was found that herpes zoster reactivation occurred when sle was inactive . the presence of varicella - zoster virus dna in the early lesions after herpes zoster eruption has been inconsistently demonstrated by pcr analysis . negative findings in the current case were in line with this statement . additionally , the negative ppd skin test confirmed the low positive rate for ppd results observed in patients with sle as described previously , suggesting a depressed cell - mediated immunity or anergy . allodynia is common in the acute phase of herpes zoster infection and predicts a higher likelihood of developing postherpetic neuralgia . cbz is widely used in the treatment of postherpetic neuralgia along with nsaid , opioid analgesics , local anesthetics and antiviral therapy . skin reactions induced by cbz are usually mild , reversible and dose related [ 8 , 9 ] . they are more likely to occur during the first 8 weeks of the treatment , when the starting dose is high or when cbz is administered with other anticonvulsants . in the case it is well known that because of genetic variations , humans differ in their response to treatments . genetic markers vary in relation to the ethnicity and the offending drug [ 8 , 10 ] . hla - b*1502 as a marker for cbz - induced sjs is well established in the han chinese population by different studies . a significant association between cbz - triggered sjs and hla - b*1502 genotype has also been demonstrated among the indians , particularly in the hindu community [ 8 , 10 , 11 ] . what makes a lesional area protected by the original disease ( herpes zoster ) and resistant to the offensive of a secondary event ( drug - induced sjs ) remains speculative . several possible pathomechanisms may be related to the virus ( vzv ) immunity , the underlying autoimmune disease ( sle ) and/or drug metabolism . it has been hypothesized that the virus could alter the skin immune system locally and elicit a predominantly th1 cytokine profile with overexpression of tnf - a , ifn- ? in addition , vzv has a variety of immune evasion mechanisms that limit the presentation of viral peptides by mhc class i and ii ; these may persist and remain hidden from the immune system . these viral peptides and/or tissue antigens altered by the virus may induce an atypical immune response . the concept of epitope spreading , whereby the tissue damage from a primary inflammatory process causes the release of previously sequestered antigen , leading to a secondary autoimmune response against the newly released antigen , may provide us with a possible explanation . in this case , there were some configurational changes within the skin antigens , perhaps due to sle or its treatment , which may have been sequestered , and it was only when another triggering event such as herpes zoster occurred that the secondary autoimmune response developed . the latter was probably altered by the concomitant use of immunosuppressive therapy . a genetic or acquired defect in the drug metabolism ( cbz ) in predisposed individuals , although plausible , does not explain the sparing of the area previously affected by an inflammatory condition . to conclude , we document a case of severe cbz hypersensitivity following herpes zoster reactivation with a reverse isotopic phenomenon in a patient presenting an interaction of two unfavorable prognostic factors : an underlying autoimmune systemic disease ( sle ) and a possible genetic predisposition . the case presented in this paper provides some insight into the possible etiological mechanisms of this rare phenomenon and the complex interplay between antiviral and antidrug immune responses .
the reverse isotopic response is a rarely encountered phenomenon . 
 the spared lesions are various and mainly inflammatory in nature , with herpes zoster infection being the most common . a novel case of stevens - johnson syndrome triggered by carbamazepine sparing the skin area previously affected by herpes zoster infection in a 39-year - old indian female with systemic lupus erythematosus is documented . 
 several features as well as possible pathomechanisms that bear discussion have emerged from this case documentation . 
 these may be related to the virus immunity , the underlying autoimmune disease ( systemic lupus erythematosus ) and/or drug metabolism .