however , in approximately 15% to 30% of adult - onset dm cases , dm represents a paraneoplastic syndrome caused by an underlying malignancy . the immune mechanisms involved in dm are undetermined , but are supported by the presence of t cells , macrophages , and dendritic cells in muscle tissue . t cells may have direct and indirect toxic effects on muscle fibers , causing muscle fiber necrosis and muscle weakness , but the target of the immune reaction is unknown . these reactions begin 4 to 21 days after the culprit drug is administered and rapidly evolve into widespread rashes , while recurrence after rechallenge begins within 2 days . this onset pattern suggests that rather than direct toxicity , sensitization and specific immunological memory occur when a dose - related threshold is reached . resolution after drug discontinuation ( known as " dechallenge " ) also helps identify the causative agent . the spectrum of medications reported to cause drug - induced exanthema is wide and includes drugs of multiple classes , most commonly antibiotics . our patient presented with dm as a paraneoplastic syndrome associated with metastatic breast cancer . two years later , she experienced an exanthematous drug eruption that was related to paclitaxel - based palliative chemotherapy . here , we describe a patient with metastatic breast cancer who developed paraneoplastic dm and an exanthematous drug eruption after exposure to paclitaxel . to the best of our knowledge , there have been few reported cases of adverse drug reactions in which morbilliform exanthema was induced by paclitaxel . in may 2011 , a 55-year - old postmenopausal woman presented to a community hospital for the evaluation of polyarthralgia and erythematous skin rashes with itching sensation . she was a never smoker and not an alcoholic , and had a history of situs inversus totalis diagnosed at the age of 33 years . the rash was initially diagnosed as rheumatic dermatitis and treated with oral steroids and antihistamines with slight improvement . at that time , a diagnostic core needle biopsy revealed invasive ductal carcinoma in the left breast ( figure 1a ) . a computed tomography scan of the chest , abdomen , and pelvis and a bone scan showed multiple lymph node metastases ( figure 2 ) . she was referred to our breast clinic for further oncologic evaluation and care . in our clinic , she was diagnosed with dm accompanying cutaneous erythematous eruptions , heliotropic rashes over both upper eyelids , gottron 's papules on both elbows , and progressive weakness / arthralgia of the upper and lower limbs . the patient 's complete blood cell count and differential , urinalysis , electrolytes , hepatitis serology , myoglobulin , anti - jo-1 antibody , extractable nuclear antigen i ( ena i ) antibody , ena ii antibody , and anti - cyclic citrullinated peptide antibody were within the normal range . alanine transaminase and lactate dehydrogenase levels were elevated ( 83 u / l and 1,560 iu / l , respectively ) . the skin biopsy specimen taken from the left hip showed perivascular lymphocyte and neutrophil infiltration with small , dark nuclei and scant cytoplasm , which was consistent with dm ( figure 3 ) . since the above test results were consistent with probable dm according to diagnostic criteria , a muscle biopsy and electromyogram were not performed . the patient was treated with systemic steroid therapy with good control of joint pain and weakness as well as partial remission of skin rashes . the breast cancer was at stage iiic ( ct1n3m0 ) as assessed using the american joint committee on cancer classification . she received palliative chemotherapy for 2 years as part of the clinical trial marriane study ( tdm1 and pertuzumab ) . she tolerated the breast cancer therapy well , with all manifestations of dm resolving after chemotherapy . after the completion of 37 sessions of palliative chemotherapy , the tumor showed further progression . skin manifestations of dm occasionally recur in association with significant stressors , but she experienced no recurrence of symptoms suggestive of myositis after chemotherapy . she subsequently received second - line taxane - based chemotherapy with paclitaxel 175 mg / m iv over 24 hours and trastuzumab 4 mg / kg , every 3 weeks . nine days after the first - cycle infusion , multiple erythemaotus maculopapular rashes developed on the whole body symmetrically sparing the palms and soles ( figure 4a ) . routine blood tests demonstrated anemia and eosinophilia ( hemoglobin 10.8 g / dl , absolute lymphocyte count 1,11610/l , neutrophil count 12.010/l , platelet count 18910/l ) . her vital signs were normal ( blood pressure , 110/68 mm hg ; heart rate , 110/min ; and temperature , 36.7 ) . there was no mucous membrane involvement ( ocular , oral , or genital lesions ) or nail change . the patient was treated with supportive management , especially systemic steroids and antihistaminics , and the skin rashes gradually resolved over 1 week . however , 5 minutes after her second - cycle infusion of paclitaxel at reduced doses , she complained of skin rashes with itching sensation on the whole body ( figure 4b ) . immediately after the cessation of paclitaxel infusion her cutaneous lesions improved , and paclitaxel therapy was then stopped after two cycles . since she was receiving no other medication , associations between exanthema and paclitaxel were suggested by the complete resolution of the skin lesions within weeks of drug withdrawal . the clinical features were consistent with a drug - induced morbilli - form exanthema , and critical assessment disclosed circumstantial evidence to implicate paclitaxel as the cause of this complication . thus , after first- and second - cycle chemotherapy , her skin rashes were diagnosed as paclitaxel - induced exanthema . , doxorubicin chemotherapy was planned , and the patient continued to have regular follow - up . the emergence of these entities may be attributed to autoantibodies generation , paraneoplastic syndromes , direct invasion of the joints and muscles by tumor cells , or combination chemotherapy . with significant advances in immunomodulatory therapies for cancer and autoimmune disease numerous investigators have attempted to understand the role of the human immune system in cancer and autoimmune disease . after a cutaneous presentation of dm associated with metastatic breast cancer , however , it is speculated that there is a possible biological association between dm and malignancy . it has been suggested that a common environmental factor may simultaneously act as a trigger of inflammation and as a carcinogen . some investigators have implicated an antitumoral immune reaction that evolves into an autoimmune syndrome through interactions between muscle and skin antigens . paclitaxel , which is thought to have caused the drug eruption in this case , is an antineoplastic agent for various malignancies . major adverse reactions include peripheral neuropathy , myelotoxicity , bradycardia and hypotension , alopecia , nausea and emesis , arthralgia and myalgia , granulocytopenia , and hypersensitivity . however , there have been few cases of exanthematous drug eruption to paclitaxel in the literature . clinicians have suspected for years that drug reactions are mediated by immune mechanisms because their occurrence suggests sensitization and specific immunological memory rather than direct toxicity . it is possible that granulysin is expressed at different levels in multiple cutaneous adverse drug reactions and that skin - infiltrating cd8 + t and nkp46 + cells are prominent sources of granulysin . a strong relationship between autoimmmunological pathogenesis and underlying malignancy has been demonstrated in the literature . for example , when patients are on long - term immunosuppressive medications , for example cyclosporine for the prevention of graft - versus - host disease after organ transplantation , the odds of cancer development is increased . patients who are immunocompromised by human immunodeficiency virus infection are more susceptible to certain malignancies , including acquired immunodeficiency syndrome - defining cancers such as kaposi sarcoma and central nervous system lymphomas as well as lung cancer and hodgkin lymphoma . in addition , similar to the introduction a novel virus into a population , cancer in transplanted organs may develop rapidly in recipients even though malignancies were unapparent or in remission in the donor . on a cellular level , t - cells in the tumor environment contribute to antitumor immune activity by interacting with antigen- presenting molecules displaying tumor - associated antigens ( taa ) , antigenic proteins expressed by a tumor that are unique , and with mutated or even normal self - proteins with upregulated expression . in response to interactions with taa , tumor - infiltrating lymphocytes ( til ) may produce effector molecules , including granzymes , perforins , cytokines , and interferon  that are directly cytotoxic to tumor cells . in a few studies , the detection of til in most tumors directly correlates with improved prognosis and patient survival , and ideally , this interaction completely eliminate the neoplasm . if the immune system does not kill the malignant growth , it may become clinically significant . conversely , successful antitumor responses may cross - react with normal self - tissues , leading to the loss of self - tolerance . consequently , if the magnitude of the immune response continues to grow , inflammatory or autoimmune disease may develop . our case report reviewed and investigated the immunological pathogenesis of dm and drug eruption , suggesting associated pathways between these entities . in conclusion , we have shown that underlying malignancy may represent a favorable soil for rare immunological reactions such as paraneoplastic dm or a cutaneous drug eruption to paclitaxel . in addition , our case underscores the importance of being vigilant for varied forms of associated immunological reactions in patients with internal malignancy . however , the exact pathophysiological mechanisms behind dm and drug eruption , as seen in our patient , have been the subject of controversy . although dm and drug eruption are allergic and immune - processes , their specific mechanisms require clarification in further studies .
dermatomyositis ( dm ) is an idiopathic autoimmune connective disease characterized by muscles and skin inflammation of and a well - recognized association with several human malignancies , especially breast cancer . 
 paclitaxel is a taxane antineoplastic agent with therapeutic effects against a wide range of cancers including breast cancer . 
 this drug is well known for neurotoxicity and hypersensitivity reactions 
 . however , cutaneous drug eruptions , especially those of grade iii or higher , are not frequent . here 
 , we describe the case of a 55-year - old woman with metastatic breast cancer who developed paraneoplastic dm and a paclitaxel - induced exanthematous drug eruption . 
 this case report emphasizes the importance of evaluating internal malignancies , such as advanced breast cancer , in newly developed dm patients . 
 in addition , it presents a rare case of paclitaxel - induced exanthematous drug eruption . 
 the purpose of this case report highlights the immunological pathogenic mechanism of dm and drug eruption in underlying advanced breast cancer .