kaposi 's varicelliform eruption is a disseminated cutaneous infection usually caused by the herpes simplex virus ( hsv ) .
it predominantly occurs in patients with pre - existing active dermatosis   and is characterized by disseminated vesiculopustules and erosions .
it is common in patients with atopic dermatitis and rarely develops in an immunocompromised host .
there have been several case reports of kaposi 's varicelliform eruption occurring in patients with cutaneous t - cell lymphoma and multiple myeloma [ 2 , 3 ] .
herein , we report a nonfatal case of kaposi 's varicelliform - like eruption occurring in an immunocompromised patient taking the mammalian target of rapamycin ( mtor ) inhibitor , everolimus , for metastatic renal cell carcinoma ( rcc ) .
a 56-year - old man presented with a 6-day history of fever , chills , and severe forehead pain and 5 days of vesicular eruptions involving the skin of the forehead , both eyelids , and nose .
the skin lesions spread to his chest , back , and bilateral upper and lower extremities over the subsequent 4 days ( fig .
he underwent radical nephrectomy and the pathologic type was clear cell carcinoma with t3n0m0 , stage iii , fuhrman grade ii .
the patient was given sorafenib 400 mg twice daily for 7 months as adjuvant treatment .
follow - up computed tomography of the abdomen and pelvis performed 8 months after surgery revealed recurrence of the lesion in the left renal fossa invading the tail of the pancreas , transverse colon , and spleen .
two months later , computed tomography showed three metastatic nodules in the liver , and the patient underwent liver metastasectomy .
after surgery , he was started on 37.5 mg of sunitinib , which he took for 7 months .
eleven months after the liver surgery , disease progression involving the liver and lungs was detected , and the patient was enrolled in a clinical trial of second - line treatment using rad001 ( everolimus ) , which he took for 19 months .
thereafter , disease progressed in his lungs and the patient took palliative sunitinib on a 4-week - on and 2-week - off schedule .
seven months later , a whole - body bone scan revealed multiple bone metastases involving the left ribs , left proximal femur , left ischium , and right iliac bone .
the patient underwent palliative radiation therapy ( 45 gy ) for the pain - causing left ribs and weight bearing both pelvic bones . after finishing the radiation therapy ,
the patient 's temperature was 38.1c , his blood pressure was 151/102 mm hg , and the pulse rate was 110 beats / min .
he had vesicles and pustules , with crusting and swelling on the skin of his forehead , both eyelids and nose .
the patient 's complete blood count revealed a white blood count of 4,640/l ( neutrophils 2,210/l , lymphocytes 1,370/l ) , hemoglobin of 13.0 g / dl , and platelet count of 79,000/l presenting mild lymphopenia and thrombocytopenia . the c - reactive protein ( crp )
was elevated at 85.8 mg / l ( normal range , 08 ) . the results of other laboratory studies , including routine biochemistry and chest x - rays , were normal .
the cd4 and cd8 lymphocyte counts were 0.28  10/l and 0.64  10/l , respectively ( cd4:cd8 ratio = 0.44 ) .
a dermatologic clinical diagnosis of kaposi 's varicelliform eruption was made based on the patient 's typical skin manifestations , including viral infection - like blisters and eruptions .
the patient was intravenously administered 250 mg of acyclovir every 8 h. twenty - four hours after initiation of treatment , there were no new vesicles , and the patient 's clinical status improved
we reconsulted the dermatologist , and skin biopsy was performed after 6 days of acyclovir .
the biopsy showed interstitial granulomatous dermatitis with a few eosinophils , extravasated red blood cells and basal vacuolization ( fig .
2 ) . there was no evidence of herpetic viral infection in the biopsy specimen .
therefore , we concluded that the patient had an everolimus - induced drug eruption manifesting as kaposi 's varicelliform eruption considering both clinical presentation and pathologic findings . after stopping everolimus ,
a follow - up bone scan of the patient revealed new spinal metastases involving the t3 and l1 vertebrae and a compression fracture of l3 .
he had palliative radiation therapy ( 42 gy ) of his thoracic and lumbar spine .
kaposi 's varicelliform eruption is characterized by dissemination of cutaneous infection of hsv , and some other viruses in patients with pre - existing dermatoses [ 2 , 4 ] .
it is also called eczema herpeticum because it is most commonly seen in patients with atopic dermatitis [ 5 , 6 ] .
kaposi 's varicelliform eruption has also been described in association not only with dermatologic conditions , such as psoriasis , lupus vulgaris , contact dermatitis , and rosacea , but also malignant diseases such as cutaneous t - cell lymphoma and multiple myeloma [ 2 , 3 , 7 ] .
there has been a single report of a patient with kaposi 's varicelliform eruption associated with a drug reaction ( phenytoin ) .
the severity of kaposi 's varicelliform eruption appears to be unrelated to the extent of the eczematous lesions , and active dermatitis is not necessary for the development of eruption .
systemic viremia involving multiple organs , including the liver , lungs , brain , gastrointestinal tract , adrenal glands , and eyes , is the major cause of morbidity and mortality .
transmission can occur through contact with infected persons or by dissemination of primary or recurrent herpes .
recurrent episodes may also occur because the virus persists in the host and periodically reactivates in the mucosa and skin ; however , the manifestations of recurrent episodes are milder and usually not systemic .
a tzanck smear can provide rapid diagnosis when it shows the characteristic epithelial multinucleated giant cells .
both biopsy and serology are of little diagnostic value , and these are not recommended as routine tests [ 5 , 9 ] .
our patient did not have pre - existing dermatitis , but was taking everolimus for the treatment of the metastatic rcc . as an mtor inhibitor , everolimus modulates t - lymphocyte homeostasis , and
the patient first took everolimus for 19 months in a clinical trial and achieved stable disease . at that time
, he only had grade 1 mucositis , insomnia , and hypertriglyceridemia but no skin manifestations of toxicity . however , when taking everolimus for a second time , he developed a drug rash and pruritus after 10 days on everolimus , which were followed by clusters of umbilicated vesiculopustules .
the exact factors for kaposi 's varicelliform eruption are still unclear . however , many studies commonly explained two factors .
a defective epidermal barrier and immunosuppression associated with either therapy or a debilitated state of the patient may lead to disseminated hsv infection . in a retrospective review of 100 atopic
dermatitis patients with kaposi 's varicelliform eruption , a high ige serum level was found to be a risk factor .
defective cytokine secretion and decreased cell - mediated immunity is important in the control of primary and recurrent hsv infections .
the suppressed immunity and the loss of the epidermal barrier function as a result of everolimus may have contributed to the development of kaposi 's varicelliform - like eruption in our patient , who had an increasing tumor burden and a worsening performance status .
some investigators have shown that markers of tumor inflammation or host immune status , such as crp and neutrophil - to - lymphocyte ratio , may be predictive to survival outcome [ 10 , 11 ] . at admission
, the patient had a high crp level , mild lymphopenia , and a relatively high neutrophil - to - lymphocyte ratio , which taken together , reflected the poor condition of the patient .
we ultimately diagnosed the patient with kaposi 's varicelliform - like eruption associated with a drug eruption based on the pathologic findings , clinical manifestations , and the clinical course of the patient after everolimus treatment .
unfortunately , we were unable to confirm a viral infection , perhaps because of delays in performing the skin biopsy and other laboratory tests .
however , we believe that the most important tool for the diagnosis of kaposi 's varicelliform eruption is clinical judgment . this is a rare case of kaposi 's varicelliform - like eruption occurring as an everolimus - induced rash .
physicians need to be aware that patients with increasing tumor activity and decreasing immunity may be at risk for this problem .
early diagnosis , stopping the suspected medication and appropriate treatment of patients at risk for viral complications are very important medical considerations .
 kaposi 's varicelliform eruption is a cutaneous eruption caused by the herpes simplex virus and a few other viruses that infect persons with pre - existing dermatosis such as atopic dermatitis . 
 we report the case of a 56-year - old man who was treated with the mammalian target of rapamycin inhibitor , everolimus , for metastatic renal cell carcinoma . 
 he presented with painful , umbilicated vesicles and pustules on his face , genital region , forearms , and legs suggestive of kaposi 's varicelliform eruption . 
 he did not have a history of any visceral viral disease and pre - existing dermatosis . 
 the diagnosis was based on the clinical features . 
 he was treated with acyclovir for 7 days , with improvement of his skin lesions . 
 we discuss the clinical manifestations of the kaposi varicelliform - like eruption in an immunocompromised patient treated with everolimus . 
Introduction
Case Report
Discussion
Disclosure Statement