Acneiform eruptions induced by cetuximab

INTRODUCTION: Many drugs may induce acneiform eruptions: vitamine B12, corticosteroids, androgens, lithium, tuberculostatics, halogens, some antidepressants, anticonvulsives and immunosuppressors. Many cases of acneiform eruptions can be observed following treatment with cetuximab, a drug used for solid cancers at advanced stages in experimental protocols. CASE REPORTS: Case 1. A 56 year-old woman, suffering from a colorectal cancer, developed a sudden acneiform eruption after 6 cures of cetuximab, at a one-week interval. She was treated with bisoprolol hemifumarate, sodium levothyroxin, cyproterone acetate and estradiol valerate. Clinical examination revealed inflammatory and follicular papulopustules localized on the face and upper chest. Comedos were absent. Itching sensations were discrete. Histopathological examination of a papulopustule revealed a folliculitis with polymorphonuclear neutrophils. PAS staining did not reveal the presence of bacteria or yeasts. Bacterial and fungal cultures were negative. Lesions faded in approximately 2 weeks following minocycline treatment (100 mg/day). Case 2. A 65 year-old man, treated by cetuximab for a colorectal adenocarcinoma, suddenly developped follicular inflammatory papulopustules on the face, trunk and extensor surfaces of both arms, after 3 weeks of treatment. Itching was discrete. Comedos were absent. Histopathology revealed the presence of a folliculitis with polymorphonuclear neutrophils. Bacteriology and mycology were negative. Lesions were partly controlled by administration of minocycline (100 mg/day) but worsened again in the days following each cure of cetuximab. DISCUSSION: Cetuximab is a monoclonal antibody binding to the epidermal-growth-factor-receptor. It is used in the treatment of solid cancers at advanced stages. Both case reports share some similarities: the development of follicular inflammatory papulopustules distributed on the face and trunk typical, of acneiform drug eruptions. Itching is discrete. Comedos are absent. Quick onset of lesions is the rule. Cetuximab can be added to the list of drugs responsible for acneiform eruption.     

Acneiform eruptions after facial beauty treatment

BACKGROUND: Female patients in the post-adolescent age group presented with predominantly deep-seated nodules and a few comedones situated mainly on the cheeks. As most of these subjects related the onset of their symptoms to antecedent facial beauty treatment, we decided to study the clinical and histologic profile of these patients. METHODS: Thirty seven subjects (36 women and one man) were questioned in detail about their acneiform eruptions. The patients were examined and a biopsy of typical lesions was taken in eight patients. RESULTS: On direct questioning, all patients related the onset of their lesions to facial beauty treatment taken 3-8 weeks previously. The predominant types of lesion were deep-seated nodules, although a few closed comedones were present in some cases. Most lesions took a long time to heal and, on healing, left behind hyperpigmentation. The cheeks were universally involved in all patients, and the chin and forehead were involved in 14. The histopathologic study revealed a predominantly peri-appendageal dermal infiltrate consisting of lymphocytes and histiocytes admixed with polymorphs. A granulomatous infiltrate was seen in one-third of the biopsies. CONCLUSIONS: This eruption is unlike the earlier eruption described as acne cosmetica in being inflammatory, indolent, and often occurring after the first cream massage itself.     

Acneiform eruptions associated with epidermal growth factor receptor-targeted chemotherapy

A relatively newer class of chemotherapy agents, known as the epidermal growth factor receptor inhibitors (EGF-RIs), is being used to treat advanced stages of solid tumors. Acneiform eruptions are a frequent adverse effect and one which has been associated with increased survival in some studies. We describe 3 patients who presented shortly after initiation of EGF-RI therapy. Characteristics included an absence of comedones, facial and truncal involvement, and a perifollicular lymphoneutrophilic infiltrate detected on biopsy. Lesion counts were reduced with topical adapalene and oral tetracyclines in two patients. Patient 3 had dramatic clearance with low-dose isotretinoin (20 mg daily) until completion of EGF-RI therapy. Acneiform eruptions are a common adverse reaction to EGF-RI therapy and can be treated with traditional acne therapy. This should not be considered a drug hypersensitivity eruption or allergy, and patients should continue therapy. For patients with severe eruptions, oral isotretinoin is a consideration.     

Acneiform eruptions caused by vitamin B12: A report of five cases and review of the literature

We describe five cases of acneiform eruption caused by vitamin B12 in five females aged 37, 32, 62, 29, and 21 years, respectively. The eruption appeared from 1 week to 5 months after the beginning of the therapy with i.m. or oral vitamin B12. Clinical picture was characterized by papules and pustules located on the face. In three patients, similar lesions were also present on the neck, shoulders, chest, and upper portion of the back. Comedones and cysts were absent. In two patients, serum vitamin B12 levels were very high. Histopathologic examination in one patient revealed an eosinophilic folliculitis. Spontaneous and complete remission was observed in all patients 3‐6 weeks after vitamin B12 discontinuation.     

Drug-Induced Acneiform Eruption

Drug-induced acne is a specific subset of acne that usually has some specific features, namely a monomorphic pattern, an unusual location of the lesions beyond the seborrheic areas, an unusual age of onset, a resistance to conventional acne therapy and, of course, the notion of a recent drug introduction. Many drugs can be responsible for such a clinical pattern. Corticosteroids, neuropsychotherapeutic drugs, antituberculosis drugs, and immunomodulating molecules are the more classical drugs associated with induced acne. Recently, new drugs, mainly targeted therapy in the field of oncology, such as epidermal growth factor receptor inhibitors, have been associated with an increased frequency of this adverse effect. Disruption of the culprit drug is rarely mandatory in cases of drug-induced acne. Close cooperation between the dermatologist and medical staff in charge of the patient is an important challenge to achieve optimal management of the initial disease.     

Acneiform follicular mucinosis

Follicular mucinosis is a rare chronic inflammatory disease of unknown aetiology, presenting as mucin deposits around the follicles and sebaceous glands. It can progress to alopecia of the scalp and other hairy areas. Follicular mucinosis may be a benign primary idiopathic disorder or secondary to malignant lymphoproliferative disorders. It can present with shiny papules or sharply marginated infiltrated erythematous scaling plaques, with follicular accentuation on the scalp, neck, trunk and limbs. There are many local and systemic treatments. This paper discusses the case of an adult with an uncommon acneiform follicular mucinosis controlled with systemic corticosteroids.     

EGFR Inhibitor-Associated Acneiform Folliculitis

Treatment with epidermal growth factor receptor (EGFR) inhibitors is associated with cutaneous adverse events, including acneiform folliculitis, dry skin, and nail disorders. Acneiform folliculitis is a class effect of EGFR inhibitors that is thought to be a direct result of EGFR blockade in the hair follicle. The folliculitis is typically mild to moderate in severity and reversible without scarring upon treatment completion. Dose modification or treatment discontinuation is rarely necessary, except in severe cases. Standard acne treatments (e.g. benzoyl peroxide, oral or topical antibacterials, retinoic acid) may provide some benefit, based on anecdotal reports. Clinicians should be aware of the possibility of superinfection with Staphylococcus aureus, in some cases involving meticillin-resistant strains, which may require treatment with oral antibacterials. Further study is needed to determine how the presence and severity of acneiform folliculitis are related to clinical outcomes, and which patients taking EGFR inhibitors are more likely to develop this disorder.     

Acneiform eruption secondary to cetuximab

C225 (cetuximab) is a monoclonal antibody that targets the epidermal growth factor receptor (EGF-R). It is used for the treatment of solid malignant tumors in advanced stages. It works against tumors by inhibiting cell proliferation, angiogenesis and the formation of metastases, as well as by promoting cell apoptosis. We present the case of a 64-year-old male patient affected with a colon neoplasm with hepatic metastases, for which treatment with cetuximab was indicated. He came to our department because of a skin eruption with papules and pustules located on the face, neck, presternal area and upper back, but with no cysts or comedones. The biopsy was compatible with an acneiform eruption. The patient was treated with minocycline, 100 mg/day for 2 weeks, with the clinical symptoms responding favorably. When he was given further doses of cetuximab, he once again presented with new eruptions, but of lesser intensity. Because of the high frequency with which this adverse effect appears, it is recommended that cetuximab be included on the list of drugs causing acneiform eruptions.     

Acneiform exanthema caused by azathioprine

An acneiform eruption due to azathioprine was demonstrated through patch-tests and through elicitation on challenge. The intrafollicular sterile inflammation with abscess formation and the direct manifestation without a sensitization period are not consistent with a normal allergic mechanism.     

Acneiform eruption induced by cetuximab

Cetuximab is a recombinant human/mouse chimeric monoclonal antibody that targets the extracellular domain of the epidermal growth factor receptor (EGFR). Cetuximab is approved by the US Food and Drug Administration for the treatment of EGFR-expressing metastatic colorectal cancer as monotherapy in patients who are intolerant to irinotecan-based chemotherapy, or in combination with irinotecan in patients who are refractory to irinotecan-based chemotherapy. Due to the important role of the EGFR in skin homeostasis, cutaneous reactions are a common adverse effect of cetuximab, mainly as acneiform follicular eruption seen in almost 85% of patients. We report on a 46-year-old female Caucasian patient with metastatic colorectal cancer, referred to our department for acneiform eruption induced by cetuximab in combination with irinotecan. Four days after the first infusion the patient developed intense acneiform eruption consisting of erythematous follicular papules and pustules spread to the face, neck and upper part of the trunk, accompanied by intense pruritus and fever (38.0 degrees C). There were no comedones. Biopsy specimen revealed superficial and florid neutrophilic suppurative folliculitis. She was treated with erythromycin tablet 600 mg, three times a day for 1 month, and topical clindamycin solution 3%. After 1 month of treatment, the lesions consistently faded, and the patient continued receiving immunochemotherapy.     

Fixed drug eruptions,bullous drug eruptions,and lichenoid drug eruptions

Drug reactions are among the most common reasons for inpatient dermatology consultation. These reactions are important to identify because discontinuation of the offending agent may lead to disease remission. With the rising use of immunomodulatory and targeted therapeutics in cancer care and the increased incidence in associated reactions to these drugs, the need for accurate identification and treatment of such eruptions has led to the development of the “oncodermatology” subspecialty of dermatology. Immunobullous drug reactions are a dermatologic urgency, with patients often losing a significant proportion of their epithelial barrier; early diagnosis is critical in these cases to prevent complications and worsening disease. Lichenoid drug reactions have myriad causes and can take several months to occur, often leading to difficulties identifying the offending drug. Fixed drug eruptions can often mimic other systemic eruptions, such as immunobullous disease and Stevens-Johnson syndrome, and must be differentiated from them for effective therapy to be initiated. We review the clinical features, pathogenesis, and treatment of immunobullous, fixed, and lichenoid drug reactions with attention to key clinical features and differential diagnosis.     

Acneiform eruption induced by lithium carbonate.

A 26-year-old female developed a severe acneiform eruption on her face, chest and back soon after she started taking lithium carbonate for psychosis. Histopathological examination revealed it to be folliculitis, rather than true acne. The eruption continued for six months but was resolved three months after discontinuing the drug. It has not reappeared in the following 3 years.     

Acneiform eruption from epidermal growth factor receptor inhibitors

One of the fundamental aims of oncological research is the search for molecules with greater efficacy against tumors and less toxicity than the usual chemotherapeutic agents. Epidermal growth factor receptor inhibitors are a new group of drugs which, because of their more specific effect against neoplastic cells, seem to meet these characteristics. Skin eruptions are one of the most frequent adverse effects associated with their use, secondary to the drug's direct inhibitory effect on homeostasis of the epidermis and of the pilosebaceous follicle. Several cases of cutaneous toxicity in patients treated with epidermal growth factor receptor inhibitors have recently been published. We present three cases of acneiform eruptions attributable to different drugs in this family (cetuximab, gefitinib and erlotinib).