|Year : 2018 | Volume
| Issue : 2 | Page : 107-116
|Unusual and interesting adverse cutaneous drug reactions
Vaishali Masatkar1, Ashok Nagure2, Lalit Kumar Gupta3
1 Department of Dermatology, Ananta Institute of Medical Sciences and Research Centre, Rajsamand, India
2 Department of Dermatology, Bidar Institute of Medical Sciences, Bidar, Karnataka, India
3 Department of Dermatology, RNT Medical College, Udaipur, Rajasthan, India
|Date of Web Publication||6-Apr-2018|
Dr. Lalit Kumar Gupta
Department of Dermatology, RNT Medical College, Udaipur, Rajasthan
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Any drug can cause any rash! Cutaneous adverse drug reactions (CADRs) are great mimickers and can be included in the differential diagnosis of any inflammatory dermatoses. Several drugs can cause rash of similar morphology and the same drug can cause rash of different morphology. While some common and specific drug reaction patterns are recognized easily by the clinicians, many a times unusual and interesting patterns can be induced by drug(s), thus leading to erroneous diagnosis and mistreatment. This review aims to familiarize clinicians with some rare, yet interesting patterns of CADR.
Keywords: Adverse cutaneous drug reactions, emerging cutaneous adverse drug reactions, newer targeted therapy, rare
|How to cite this article:|
Masatkar V, Nagure A, Gupta LK. Unusual and interesting adverse cutaneous drug reactions. Indian J Dermatol 2018;63:107-16
What was known?
- Cutaneous adverse drug reactions are commonly encountered clinical problem by dermatologists.
- They can mimic a wide variety of inflammatory dermatoses.
- Exanthematous rash, urticaria/angioedema and fixed drug reactions are the commonest reaction patterns of drug reactions and are easily recognized.
| Introduction|| |
Adverse drug reactions are one of the major preventable public health problems. They are common but are underreported and underrecognized cause of morbidity and mortality. As the longevity of population increases with a large subset belonging to elderly on multiple drugs and with the advent of newer drugs, the probability of encountering drug reaction is on the rise. The world of cutaneous adverse drug reactions (CADRs) is wide and enigmatic and almost any inflammatory or noninflammatory dermatosis can be mimicked. Thus, the aphorism – “Anything you see, anything you think, and something that you don't even think of could be due to drugs!!”
In this article, we have included some rare, unusual, interesting, and diagnostically challenging adverse drug reactions. For the sake of convenience, they are classified into:
- ADRs to commonly used drugs which are generally considered safe
- Atypical presentations of some common classical ADR
- Typical CADRs, although not very common, which are interesting morphologically
- CADR to newer targeted therapy/emerging CADR
- Drugs causing induction of malignancy
- Some interesting hair- and nail-related ADR and
- Paradoxical drug reactions (PDRs).
Adverse drug reactions to commonly used drugs generally considered safe
This group comprises drugs which are commonly used, sometimes over-the-counter, are usually considered safe and often excluded when a patient on multiple drugs develop a drug reaction. Some of these drugs are frequently used in the treatment of adverse drug reactions, so clinicians should have a high index of suspicion and should be aware of the possibility of reactions to these drugs.
Anaphylaxis to ranitidine
So far, at least 10 cases of anaphylaxis have been reported with ranitidine, both oral  and intravenous preparation (bolus ,,,, as well as slow infusion ,). Most of the reactions have occurred within minutes; in one case though, it was delayed up to 90 min. The clinical manifestations include skin rash, pruritus, angioedema, wheezing, dyspnea, tachycardia, hypotension, irritability, deterioration or loss of consciousness, drowsiness, and right bundle branch block in varying combination. Most of the patients can be resuscitated with inotropic and ventilator support. One patient, however, died within 30 min despite intensive resuscitation attempts. Oral challenge test, skin prick test, intradermal test, and specific serum IgE are used for confirmation of diagnosis.
The first case was reported in 1991 when a 53-year-old male developed bilateral gynecomastia and mastodynia following 8 weeks of omeprazole therapy for duodenal ulcer. The gynecomastia regressed after 4 weeks of drug termination and was reproduced 6 weeks after drug reintroduction. In a retrospective review of cases of gynecomastia from the “Spanish Pharmacovigilance system,” 24 patients on treatment with omeprazole were identified as having gynecomastia in the 2007 year database. Here, the relative odds ratio for omeprazole exposure showed a statistically significant elevation in comparison to those with no exposure.
Hypersensitivity reactions to glucocorticoids
Glucocorticoids and the excipients contained in commercial corticosteroid formulations are able to induce severe immediate type as well as delayed type hypersensitivity reactions. The overall prevalence of type I steroid hypersensitivity is estimated to be 0.3%–0.5%. Allergic contact dermatitis is the most commonly reported nonimmediate hypersensitivity reaction and usually follows topical corticosteroid (CS) application but has also been reported with parenteral CS. As glucocorticoids are the most widely used drugs for the treatment of hypersensitivity, it is even more so important to consider an allergy to CS in patients with worsening anaphylactic symptoms after administration of systemic CS.
Fixed drug eruption to antihistamines
Antihistamines form a sizeable proportion of dermatology prescriptions. There have been a few reports of fixed drug eruption (FDE) with piperazine derivatives (hydroxyzine,, cetirizine,, and levocetirizine ) and they are also known to show cross-reactions on patch test. This cross-reaction is not observed with piperidine derivatives (fexofenadine, ebastine, loratadine, and astemizole). Multilocalized bullous FDE has also been described with cetirizine.
This group includes atypical morphological variants of common adverse drug reactions which can pose diagnostic challenge at times.
Nonpigmenting fixed drug eruption
Residual pigmentation is one of the characteristic features of FDE and is often a supportive diagnostic clue in patients with recurrent episodes. Nonpigmenting FDE has been reported in association with pseudoephedrine, co-trimoxazole, tetrahydrozoline, diflunisal, thiopental, piroxicam, iothalamate, arsephenamine, paracetamol, intra-articular triamcinolone acetonide, eperisone hydrochloride, furazolidone, and acetaminophen. Recently, reports of nonpigmenting FDE to eprazinone, sorafenib, tadalafil, esomeprazole, and fluoroquinolones  have also been described. The lesions can be as large as over 10 cm and multiple lesions possibly represent abortive variant of toxic epidermal necrolysis (TEN).
Postcoital fixed drug eruption
A 34-year-old male patient developed FDE on the glans penis after sexual intercourse with wife on trimethoprim-sulfamethoxazole. Similar reaction has also been reported with wife using sulfathiazole/sulfacetamide/sulfabenzamide (triple-sulfa) vaginal cream.
Bullous Sweet's syndrome
An HIV-positive patient developed a bullous eruption soon after each cycle of interleukin-2 (IL-2). Histopathology was suggestive of Sweet's syndrome. The same patient developed pseudolymphatous reaction on restarting the therapy after 5 years, and it resolved after discontinuation.
Acute localized exanthematous pustulosis
Acute localized exanthematous pustulosis (ALEP) is a rare variant of AGEP (acute generalized exanthematous pustulosis). A pregnant female developed sterile pustules localized over right breast, fever, and malaise with oral clindamycin. Other medications which are reported to cause ALEP include amoxicillin, amoxicillin-clavulanic acid, cephalosporins, sulfamethoxazole-trimethoprim, levofloxacin, paracetamol, ibuprofen, nimesulide, finasteride, docetaxel, and sorafenib.
Cutaneous adverse drug reactions with interesting morphology
Symmetrical drug-related intertriginous and flexural exanthema or Baboon syndrome
Baboon syndrome is a distinctive skin reaction, in which the patient typically develops erythematous buttocks that appear similar to those of a baboon. The noncontact allergenic variant of Baboon syndrome is also referred to as symmetrical drug-related intertriginous and flexural exanthema (SDRIFE). The diagnostic criteria of SDRIFE include:
- Exposure to a systemically administered drug either at the first or repeated dose
- Sharply demarcated erythema of the gluteal/perianal area and/or V-shaped erythema of the inguinal/perigenital area
- Involvement of at least another intertriginous/flexural localization
- Symmetry of affected areas
- Absence of systemic symptoms and signs.
SDRIFE has been reported with multiple medications including antibacterials (erythromycin, penicillins, and aminoglycosides), antifungals, allopurinol, antiasthma treatments (aminophylline, terbutaline), and radiocontrast media.,,
Flagellate erythema and pigmentation
Flagellate erythema is a distinctive morphologic presentation of linear, whiplash-like pattern, red streaks on the skin which usually leaves residual postinflammatory hyperpigmentation behind. It has been described with antineoplastic agents including bleomycin ,,,,,,,, (most commonly), bendamustine, docetaxel, peplomycin, and trastuzumab. Other conditions which may lead to flagellate dermatoses include chikungunya fever, parvovirus B19 infection, hypereosinophilic syndrome, inflictions and abuse, phytophotodermatitis, paederus dermatitis, toxin-induced (mushroom, shiitake), and rheumatologic conditions (SLE, dermatomyositis, and adult-onset Still's disease).
Red man syndrome
Red man syndrome encompasses a constellation of symptoms ranging from a mild reaction such as flushing, urticarial rash, and/or pruritus to a serious reaction such as generalized erythema, intense pruritus, and even hypotension. Signs appear about 4–10 min after start of infusion or may begin soon after its completion. It is often associated with rapid (<1 h) infusion of the first dose of vancomycin.
Capillary leak syndrome
Capillary leak syndrome (CLS) is characterized by acute episodes of generalized edema, hemoconcentration, hypoproteinemia, and severe hypotension. The etiopathogenesis is unclear. Scintigraphy with labeled albumin showed increased vascular permeability and albumin retention in extravascular space. Many drugs are known to induce CLS, including IL-2, IL-11, gemcitabine, doxorubicin, granulocyte colony-stimulating factor, interferon, and acitretin.,
Hand–foot skin reaction
Classic hand-foot syndrome has been described with the use of various chemotherapeutic agents, including sunitinib, cabozantinib, sorafenib, regorafenib, cytarabine, capecitabine, doxorubicin hydrochloride, and fluorouracil., It generally starts with prodromal symptoms of tingling and numbness on the palms and soles, and sometimes a painful sensation induced on touching hot objects, hence also known as palmoplantar erythrodysesthesia. This is followed by three phases: the inflammatory phase, characterized by erythema, desquamation and blisters with a perilesional erythematous rim; the hyperkeratotic phase, marked by the appearance of new lesions that become hyperkeratotic and development of pain in the older, hyperkeratotic areas; and the resolution phase, typified by clearing of the lesions as a result of dose modification or drug termination.
Cutaneous adverse drug reactions to newer targeted therapy/emerging cutaneous adverse drug reactions
The past several decades have seen the advent and rapidly expanding use of biological agents in the treatment of chronic diseases. As increasingly, large pools of patients have been enrolled in treatment protocols using these agents, physicians have become acquainted with both desired and adverse events associated with their use. Dermatologists frequently encounter patients affected by cutaneous drug reactions associated with the use of biological agents, and should therefore be familiar with the full range of side effects. [Table 1] enlists CADRs to newer targeted chemotherapeutic drugs.
Drugs inducing malignancies
Immunosuppressed patients experience an increased incidence of cutaneous neoplasms including melanoma, nonmelanoma skin cancer, and cutaneous lymphoproliferative disorders. The common drugs which are associated with induction of malignancy are mentioned in [Table 2]. The ones with definite risk are mentioned in bold.
Hair- and nail-related adverse drug reactions
Drug can affect hair in many ways, most common being in the form of hair loss. [Table 3] enumerates some unusual ADRs related to hair and the drugs commonly implicated in their causation.
|Table 3: Some unusual and uncommon hair-related adverse drug reactions and common causative drugs|
Click here to view
Nail abnormalities due to drugs generally occur as a part of symptom complex with coexistent skin and mucosal lesions. Pigmentary abnormalities and asymptomatic growth rate changes are the most commonly observed nail changes and reverse on discontinuation of the causative agent. The changes are often more readily observed on the nails of the thumbs and great toes, and on the fingernails, than on the toenails. The clinical features are dependent on the area of nail unit damaged. [Table 4] enlists some of the unusual ADRs related to nail and their causative agent.
|Table 4: Unusual nail-related adverse drug reactions and drugs implicated in causation|
Click here to view
PDRs are nonallergic drug reactions with an outcome of treatment opposite to the expected one. Common examples of PDRs include:
- Jarisch–Herxheimer reaction (JHR): The reproduction or aggravation of infectious disease symptoms following antibiotic treatment is known as JHR. The clinical symptoms include chills, fever, headache, myalgia, and exacerbation of mucocutaneous lesions. JHR has been described for syphilis, borreliosis, leptospirosis, mycobacterial diseases, and Q-fever among others.
- Immune reconstitution inflammatory syndrome (IRIS): noted in HIV/AIDS patients during highly active antiretroviral therapy. Symptoms include fever, progressive lymphadenopathy, and worsening or newly detected radiological findings of tuberculosis
- Chloroquine and hydroxychloroquine are antimalarial drugs used to treat polymorphic light eruption. In rare cases, however, these drugs can cause photodermatosis resembling polymorphic light eruption 
- Azathioprine and methotrexate are used in the treatment of Stevens–Johnson syndrome/TEN (SJS/TEN), but are also known to induce it ,
- Tumor necrosis factor α (TNF-α) inhibitors have become an established therapy for moderate-to-severe plaque-type psoriasis also used for systemic lupus erythematosus and SJS/TEN. However, plaque psoriasis, nail psoriasis, intertriginous, erythrodermic, and palmoplantar pustular psoriasis may be induced or aggravated with a mean time of 9.5 months after initiation of TNF-α inhibitors. TNF-α inhibitors induced lupus-like syndrome is also reported , and these drugs may also induce SJS/TEN in rare cases ,
- Inhibitors of epidermal growth factor receptor (EGFR) are targeted chemotherapeutic agents approved for different cancer entities including squamous cell carcinoma of the head and neck. Hair follicles express EGFR. Trichomegaly and hypertrichosis are adverse effects. PDR include nonscarring alopecia in the form of patchy or frontal alopecia which occurs usually with a delay of 2–3 months after initiation of treatment 
- Inhibitors (vemurafenib and dabrafenib) are used for the treatment of advanced melanoma. Related to a paradoxical activation of mitogen-activated protein-kinases signal transduction, patients can develop acantholytic dyskeratosis resembling Grover's disease.,
- There are no biologically safe drugs and any drug can cause any rash
- Drugs being used in the treatment of drug reactions such as antihistamines, steroids, and inotropic drugs can also cause CADR and a high index of suspicion is required as continuing them can have serious consequences
- Some drug reactions have typical morphology which helps the clinician in making the diagnosis, deviation from which leads to diagnostic dilemma and delay in withdrawal of offending agent and treatment. Nonpigmenting FDE is a common example of such scenario
- Morphological patterns of some CADRs make them interesting. These include flagellate pigmentation, SDRIFE, capillary leak syndrome, and hand-foot skin reaction. The presentation may be benign as in flagellate pigmentation or associated with grave prognosis as in capillary leak syndrome
- Newly introduced drugs are continuously adding to the already vast variety of CADRs indicating even more so that they are something to be closely looked for
- Induction of cutaneous malignancy is a serious side effect of some immune-modulatory drugs including biologicals
- Hair and nail changes, especially when occur in isolation or as initial manifestation, are often refuted to be caused by drugs. Pigmentary abnormalities and asymptomatic growth rate changes are the most commonly observed nail changes and reverse on discontinuation of causative agent. Others are infrequent and include transient nail shedding to permanent nail deformities
- PDRs are no rarities. In particular, paradoxical IRIS and induction of psoriasis by biologicals are being observed in increasing numbers
- It is almost disheartening and cruel that what may appear like an interesting drug reaction or observation to a clinician is never interesting for the patient.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Koh YI, Park HS, Choi IS. Ranitidine-induced anaphylaxis: Detection of serum specific IgE antibody. Allergy 2006;61:269-70.
Demirkan K, Bozkurt B, Karakaya G, Kalyoncu AF. Anaphylactic reaction to drugs commonly used for gastrointestinal system diseases: 3 case reports and review of the literature. J Investig Allergol Clin Immunol 2006;16:203-9.
Vyas VH, Mohite SN, Khatavkar SS, Jagtap SR. Ranitidine anaphylaxis: A rare occurrence. Indian J Anaesth 2011;55:425-6.
] [Full text]
Aouam K, Bouida W, Ben Fredj N, Chaabane A, Boubaker H, Boukef R, et al.
Severe ranitidine-induced anaphylaxis: A case report and literature review. J Clin Pharm Ther 2012;37:494-6.
Sripriya R, Kumar VR, Prabhu R, Ravishankar M. Intraoperative anaphylaxis to ranitidine during cesarean section. J Nat Sci Biol Med 2013;4:257-9.
Chopra D, Arora P, Khan S, Dwivedi S. Anaphylaxis following intravenous ranitidine: A rare adverse reaction of a common drug. Indian J Pharmacol 2014;46:234-6.
] [Full text]
Oliva A, Partemi S, Arena V, De Giorgio F, Colecchi C, Fucci N, et al.
Fatal injection of ranitidine: A case report. J Med Case Rep 2008;2:232.
Antonicelli L, Stagnozzi G, Massaccesi C, Manfredi M, Valentini M, Campi P, et al.
Intraoperative anaphylaxis: A case report of allergy to ranitidine. Eur Ann Allergy Clin Immunol 2012;44:253-5.
Carvajal A, Macias D, Gutiérrez A, Ortega S, Sáinz M, Martín Arias LH, et al.
Gynaecomastia associated with proton pump inhibitors: A case series from the Spanish pharmacovigilance system. Drug Saf 2007;30:527-31.
Convens C, Verhelst J, Mahler C. Painful gynaecomastia during omeprazole therapy. Lancet 1991;338:1153.
Vatti RR, Ali F, Teuber S, Chang C, Gershwin ME. Hypersensitivity reactions to corticosteroids. Clin Rev Allergy Immunol 2014;47:26-37.
Laberge L, Pratt M. Immediate and delayed hypersensitivity to systemic corticosteroids: 2 case reports. Dermatitis 2012;23:288-90.
Assouère MN, Mazereeuw-Hautier J, Bonafé JL. Cutaneous drug eruption with two antihistaminic drugs of a same chemical family: Cetirizine and hydroxyzine. Ann Dermatol Venereol 2002;129:1295-8.
Cohen HA, Barzilai A, Matalon A, Harel L, Gross S. Fixed drug eruption of the penis due to hydroxyzine hydrochloride. Ann Pharmacother 1997;31:327-9.
Kränke B, Kern T. Multilocalized fixed drug eruption to the antihistamine cetirizine. J Allergy Clin Immunol 2000;106:988.
Gupta LK, Agarwal N, Khare AK, Mittal A. Fixed drug eruption to levocetirizine and cetirizine. Indian J Dermatol 2014;59:411-3.
] [Full text]
Jhaj R, Asati DP, Chaudhary D. Fixed drug eruption due to levocetirizine. J Pharmacol Pharmacother 2016;7:109-11.
] [Full text]
Cravo M, Gonçalo M, Figueiredo A. Fixed drug eruption to cetirizine with positive lesional patch tests to the three piperazine derivatives. Int J Dermatol 2007;46:760-2.
Vidal C, Prieto A, Pérez-Carral C, Armisén M. Nonpigmenting fixed drug eruption due to pseudoephedrine. Ann Allergy Asthma Immunol 1998;80:309-10.
Rasi A, Khatami A. Unilateral non-pigmenting fixed drug eruption associated with cotrimoxazole. Dermatol Online J 2006;12:12.
Montoro J, Díaz M, Genís C, Lozano A, Bertomeu F. Non-pigmenting cutaneous-mucosal fixed drug eruption due to piroxicam. Allergol Immunopathol (Madr) 2003;31:53-5.
Choonhakarn C. Non-pigmenting fixed drug eruption: A new case due to eperisone hydrochloride. Br J Dermatol 2001;144:1288-9.
Tanabe K, Amoh Y, Mii S, Eto H, Iwamura M, Katsuoka K, et al.
Non-pigmenting fixed drug eruption induced by sorafenib. Acta Derm Venereol 2010;90:307.
Das S, Das S, Chowdhury J, Bhanja DC. Non pigmenting mucosal fixed drug eruption due to tadalafil: A report of two cases. Indian Dermatol Online J 2014;5:167-9.
] [Full text]
Gupta LK, Beniwal R, Khare AK, Mittal A, Mehta S, Balai M, et al.
Non-pigmenting fixed drug eruption due to fluoroquinolones. Indian J Dermatol Venereol Leprol 2017;83:108-12.
] [Full text]
Gruber F, Stasić A, Lenković M, Brajac I. Postcoital fixed drug eruption in a man sensitive to trimethoprim-sulphamethoxazole. Clin Exp Dermatol 1997;22:144-5.
Zargooshi J, Kavoussi H, Rahmanian E, Motaee H, Kohzadi M, Nourizad S, et al.
Postcoital penile drug eruption in a co-trimoxazole-sensitive patient following vaginal use of triple sulfa vaginal cream by his partner. J Sex Med 2012;9:758-60.
Rondina A, Watson AC. Bullous Sweet's syndrome and pseudolymphoma precipitated by IL-2 therapy. Cutis 2010;85:206-13.
De Cruz R, Ferguson J, Wee JS, Akhras V. Acute localised exanthematous pustulosis (ALEP) induced by clindamycin in pregnancy. Australas J Dermatol 2015;56:e55-8.
Shuttleworth D. A localized, recurrent pustular eruption following amoxycillin administration. Clin Exp Dermatol 1989;14:367-8.
Wohl Y, Goldberg I, Sharazi I, Brenner S. A case of paracetamol-induced acute generalized exanthematous pustulosis in a pregnant woman localized in the neck region. Skinmed 2004;3:47-9.
Tresch S, Cozzio A, Kamarashev J, Harr T, Schmid-Grendelmeier P, French LE, et al.
T cell-mediated acute localized exanthematous pustulosis caused by finasteride. J Allergy Clin Immunol 2012;129:589-94.
Elmariah SB, Cheung W, Wang N, Kamino H, Pomeranz MK. Systemic drug-related intertriginous and flexural exanthema (SDRIFE). Dermatol Online J 2009;15:3.
Winnicki M, Shear NH. A systematic approach to systemic contact dermatitis and symmetric drug-related intertriginous and flexural exanthema (SDRIFE): A closer look at these conditions and an approach to intertriginous eruptions. Am J Clin Dermatol 2011;12:171-80.
Huynh T, Hughey LC, McKay K, Carney C, Sami N. Systemic drug-related intertriginous and flexural exanthema from radio contrast media: A series of 3 cases. JAAD Case Rep 2015;1:147-9.
Changal KH, Raina H, Changal QH, Raina M. Bleomycin-induced flagellate erythema: A rare and unique drug rash. West Indian Med J 2014;63:807-9.
Lu CC, Lu YY, Wang QR, Wu CH. Bleomycin-induced flagellate erythema. Balkan Med J 2014;31:189-90.
Lee HY, Lim KH, Ryu Y, Song SY. Bleomycin-induced flagellate erythema: A case report and review of the literature. Oncol Lett 2014;8:933-5.
Khmamouche MR, Debbagh A, Mahfoud T, Aassab R, Lkhoyaali S, Ichou M, et al.
Flagellate erythema secondary to bleomycin: A new case report and review of the literature. J Drugs Dermatol 2014;13:983-4.
Eungdamrong J, McLellan B. Flagellate erythema. Dermatol Online J 2013;19:20716.
Mota GD, Penna AM, Soares RC, Baiocchi OC. Bleomycin-induced flagellate dermatitis. Rev Bras Hematol Hemoter 2014;36:297-9.
Vennepureddy A, Siddique MN, Odaimi M, Terjanian T. Bleomycin-induced flagellate erythema in a patient with Hodgkin's lymphoma – A case report and review of literature. J Oncol Pharm Pract 2016;22:556-60.
Biswas A, Chaudhari PB, Sharma P, Singh L, Julka PK, Sethuraman G, et al.
Bleomycin induced flagellate erythema: Revisiting a unique complication. J Cancer Res Ther 2013;9:500-3.
Chen YB, Rahemtullah A, Breeden E, Hochberg EP. Bleomycin-induced flagellate erythema. J Clin Oncol 2007;25:898-900.
Mahmoud BH, Eide MJ. Bendamustine-induced “flagellate dermatitis”. Dermatol Online J 2012;18:12.
Tallon B, Lamb S. Flagellate erythema induced by docetaxel. Clin Exp Dermatol 2008;33:276-7.
Araki Y, Tamura K, Seita M. Side effects of peplomycin. Gan To Kagaku Ryoho 1986;13:2446-50.
Cohen PR. Trastuzumab-associated flagellate erythema: Report in a woman with metastatic breast cancer and review of antineoplastic therapy-induced flagellate dermatoses. Dermatol Ther (Heidelb) 2015;5:253-64.
Myers AL, Gaedigk A, Dai H, James LP, Jones BL, Neville KA, et al.
Defining risk factors for red man syndrome in children and adults. Pediatr Infect Dis J 2012;31:464-8.
Kai-Feng W, Hong-Ming P, Hai-Zhou L, Li-Rong S, Xi-Yan Z. Interleukin-11-induced capillary leak syndrome in primary hepatic carcinoma patients with thrombocytopenia. BMC Cancer 2011;11:204.
Estival JL, Dupin M, Kanitakis J, Combemale P. Capillary leak syndrome induced by acitretin. Br J Dermatol 2004;150:150-2.
Strumberg D, Awada A, Hirte H, Clark JW, Seeber S, Piccart P, et al.
Pooled safety analysis of BAY 43-9006 (sorafenib) monotherapy in patients with advanced solid tumours: Is rash associated with treatment outcome? Eur J Cancer 2006;42:548-56.
Susser WS, Whitaker-Worth DL, Grant-Kels JM. Mucocutaneous reactions to chemotherapy. J Am Acad Dermatol 1999;40:367-98.
Autier J, Escudier B, Wechsler J, Spatz A, Robert C. Prospective study of the cutaneous adverse effects of sorafenib, a novel multikinase inhibitor. Arch Dermatol 2008;144:886-92.
Macdonald JB, Macdonald B, Golitz LE, LoRusso P, Sekulic A. Cutaneous adverse effects of targeted therapies: Part I: Inhibitors of the cellular membrane. J Am Acad Dermatol 2015;72:203-18.
Hammond-Thelin LA. Cutaneous reactions related to systemic immunomodulators and targeted therapeutics. Dermatol Clin 2008;26:121-59, ix.
Belloni B, Schönewolf N, Rozati S, Goldinger SM, Dummer R. Cutaneous drug eruptions associated with the use of new oncological drugs. Chem Immunol Allergy 2012;97:191-202.
Baas JM, Krens LL, Guchelaar HJ, Ouwerkerk J, de Jong FA, Lavrijsen AP, et al.
Recommendations on management of EGFR inhibitor-induced skin toxicity: A systematic review. Cancer Treat Rev 2012;38:505-14.
Rodriguez NA, Ascaso FJ. Trichomegaly and poliosis of the eyelashes during cetuximab treatment of metastatic colorectal cancer. J Clin Oncol 2011;29:e532-3.
Hu JC, Sadeghi P, Pinter-Brown LC, Yashar S, Chiu MW. Cutaneous side effects of epidermal growth factor receptor inhibitors: Clinical presentation, pathogenesis, and management. J Am Acad Dermatol 2007;56:317-26.
Watters AL, Epstein JB, Agulnik M. Oral complications of targeted cancer therapies: A narrative literature review. Oral Oncol 2011;47:441-8.
Lacouture ME, Anadkat MJ, Bensadoun RJ, Bryce J, Chan A, Epstein JB, et al.
Clinical practice guidelines for the prevention and treatment of EGFR inhibitor-associated dermatologic toxicities. Support Care Cancer 2011;19:1079-95.
Lee WJ, Lee JL, Chang SE, Lee MW, Kang YK, Choi JH, et al.
Cutaneous adverse effects in patients treated with the multitargeted kinase inhibitors sorafenib and sunitinib. Br J Dermatol 2009;161:1045-51.
Macdonald JB, Macdonald B, Golitz LE, LoRusso P, Sekulic A. Cutaneous adverse effects of targeted therapies: Part II: Inhibitors of intracellular molecular signaling pathways. J Am Acad Dermatol 2015;72:221-36.
Vanneste L, Wolter P, Van den Oord JJ, Stas M, Garmyn M. Cutaneous adverse effects of BRAF inhibitors in metastatic malignant melanoma, a prospective study in 20 patients. J Eur Acad Dermatol Venereol 2015;29:61-8.
Belum VR, Fischer A, Choi JN, Lacouture ME. Dermatological adverse events from BRAF inhibitors: A growing problem. Curr Oncol Rep 2013;15:249-59.
Zimmer L, Livingstone E, Hillen U, Dömkes S, Becker A, Schadendorf D, et al.
Panniculitis with arthralgia in patients with melanoma treated with selective BRAF inhibitors and its management. Arch Dermatol 2012;148:357-61.
Patrizi A, Venturi M, Dika E, Maibach H, Tacchetti P, Brandi G, et al.
Cutaneous adverse reactions linked to targeted anticancer therapies bortezomib and lenalidomide for multiple myeloma: New drugs, old side effects. Cutan Ocul Toxicol 2014;33:1-6.
Gerecitano J, Goy A, Wright J, MacGregor-Cortelli B, Neylon E, Gonen M, et al.
Drug-induced cutaneous vasculitis in patients with non-Hodgkin lymphoma treated with the novel proteasome inhibitor bortezomib: A possible surrogate marker of response? Br J Haematol 2006;134:391-8.
Kamba T, McDonald DM. Mechanisms of adverse effects of anti-VEGF therapy for cancer. Br J Cancer 2007;96:1788-95.
Chen HX, Cleck JN. Adverse effects of anticancer agents that target the VEGF pathway. Nat Rev Clin Oncol 2009;6:465-77.
Gotlib V, Khaled S, Lapko I, Mar N, Saif MW. Skin rash secondary to bevacizumab in a patient with advanced colorectal cancer and relation to response. Anticancer Drugs 2006;17:1227-9.
Sekulic A, Migden MR, Oro AE, Dirix L, Lewis KD, Hainsworth JD, et al.
Efficacy and safety of vismodegib in advanced basal-cell carcinoma. N
Engl J Med 2012;366:2171-9.
Aasi S, Silkiss R, Tang JY, Wysong A, Liu A, Epstein E, et al.
New onset of keratoacanthomas after vismodegib treatment for locally advanced basal cell carcinomas: A report of 2 cases. JAMA Dermatol 2013;149:242-3.
Wolverton SE, editor. Drug induced malignancy. In: Comprehensive Dermatologic Drug Therapy. 3rd
ed. New York, NY, USA:W. B. Saunders Company; 2013. p. 701-9.
Smith KJ, Skelton HG. Rapid onset of cutaneous squamous cell carcinoma in patients with rheumatoid arthritis after starting tumor necrosis factor alpha receptor IgG1-Fc fusion complex therapy. J Am Acad Dermatol 2001;45:953-6.
Ly L, Czarnecki D. The rapid onset of multiple squamous cell carcinomas during etanercept treatment for psoriasis. Br J Dermatol 2007;157:1076-8.
Keystone E, Fleischmann R, Emery P, Furst DE, van Vollenhoven R, Bathon J, et al.
Safety and efficacy of additional courses of rituximab in patients with active rheumatoid arthritis: An open-label extension analysis. Arthritis Rheum 2007;56:3896-908.
Robak E, Biernat W, Krykowski E, Jeziorski A, Robak T. Merkel cell carcinoma in a patient with B-cell chronic lymphocytic leukemia treated with cladribine and rituximab. Leuk Lymphoma 2005;46:909-14.
Faguer S, Launay F, Ysebaert L, Mailhol C, Estines-Chartier O, Lamant L, et al.
Acute cutaneous T-cell lymphoma transformation during treatment with alemtuzumab. Br J Dermatol 2007;157:841-2.
Janssens A, Berth M, De Paepe P, Verhasselt B, Van Roy N, Noens L, et al.
EBV negative Richter's syndrome from a coexistent clone after salvage treatment with alemtuzumab in a CLL patient. Am J Hematol 2006;81:706-12.
Tosti A, Pazzaglia M. Drug reactions affecting hair: Diagnosis. Dermatol Clin 2007;25:223-31, vii.
Bublin JG, Thompson DF. Drug-induced hair colour changes. J Clin Pharm Ther 1992;17:297-302.
Yun SK, Song KH, Hwang SR, Kim HU, Lee NR, Park J, et al.
Hair graying and loss induced by imatinib mesylate. J Dermatol 2014;41:107-8.
Mariani S, Abruzzese E, Basciani S, Fiore D, Persichetti A, Watanabe M, et al.
Reversible hair depigmentation in a patient treated with imatinib. Leuk Res 2011;35:e64-6.
Bezzina C, Bondon-Guitton E, Montastruc JL. Inhaled corticosteroid-induced hair depigmentation in a child. J Drugs Dermatol 2013;12:119-20.
Dika E, Patrizi A, Ribero S, Fanti PA, Starace M, Melotti B, et al.
Hair and nail adverse events during treatment with targeted therapies for metastatic melanoma. Eur J Dermatol 2016;26:232-9.
Seckin D, Yildiz A. Repigmentation and curling of hair after acitretin therapy. Australas J Dermatol 2009;50:214-6.
Ward PD, Miller HL, Shipman AR. A case of repigmentation and curling of hair on acitretin therapy. Clin Exp Dermatol 2014;39:91-2.
Clarke JT, Price H, Clarke S, George R, Miller JJ. Acquired kinking of the hair caused by acitretin. J Drugs Dermatol 2007;6:937-8.
Baran R, Fouilloux B, Robert C. Drug-induced nail changes. In: Baran R, de Berker DA, Holzberg M, Thomas L, editors. Baran and Dawber's Diseases of the Nails and Their Management. 4th
ed. Singapore: Wiley-Blackwell; 2012. p. 413-35.
Robert C, Sibaud V, Mateus C, Verschoore M, Charles C, Lanoy E, et al.
Nail toxicities induced by systemic anticancer treatments. Lancet Oncol 2015;16:e181-9.
Minisini AM, Tosti A, Sobrero AF, Mansutti M, Piraccini BM, Sacco C, et al.
Taxane-induced nail changes: Incidence, clinical presentation and outcome. Ann Oncol 2003;14:333-7.
Onder M, Oztaş MO, Oztaş P. Isotretinoin-induced nail fragility and onycholysis. J Dermatolog Treat 2001;12:115-6.
Piraccini BM, Alessandrini A. Drug-related nail disease. Clin Dermatol 2013;31:618-26.
Griffiths WA. 'Curly nails' an unusual side-effect of etretinate. J Dermatol Treat 1990;1:265-6.
Belum GR, Belum VR, Chaitanya Arudra SK, Reddy BS. The Jarisch-Herxheimer reaction: Revisited. Travel Med Infect Dis 2013;11:231-7.
Pareek A, Khopkar U, Sacchidanand S, Chandurkar N, Naik GS. Comparative study of efficacy and safety of hydroxychloroquine and chloroquine in polymorphic light eruption: A randomized, double-blind, multicentric study. Indian J Dermatol Venereol Leprol 2008;74:18-22.
] [Full text]
Métayer I, Balguerie X, Courville P, Lauret P, Joly P. Photodermatosis induced by hydroxychloroquine: 4 cases. Ann Dermatol Venereol 2001;128:729-31.
Mori H, Yamanaka K, Kaketa M, Tamada K, Hakamada A, Isoda K, et al.
Drug eruption caused by azathioprine: Value of using the drug-induced lymphocytes stimulation test for diagnosis. J Dermatol 2004;31:731-6.
Gogia A, Pathania S, Das P, Gupta YK, Bakhshi S. Methotrexate-induced toxic epidermal necrolysis in a child. Indian J Dermatol 2013;58:161.
] [Full text]
Wollina U, Hansel G, Koch A, Schönlebe J, Köstler E, Haroske G, et al.
Tumor necrosis factor-alpha inhibitor-induced psoriasis or psoriasiform exanthemata:First 120 cases from the literature including a series of six new patients. Am J Clin Dermatol 2008;9:1-4.
Moulis G, Sommet A, Lapeyre-Mestre M, Montastruc JL; Association Française des Centres Régionaux de PharmacoVigilance. Is the risk of tumour necrosis factor inhibitor-induced lupus or lupus-like syndrome the same with monoclonal antibodies and soluble receptor? A case/non-case study in a nationwide pharmacovigilance database. Rheumatology (Oxford) 2014;53:1864-71.
Fernando SL. The management of toxic epidermal necrolysis. Australas J Dermatol 2012;53:165-71.
Salama M, Lawrance IC. Stevens-Johnson syndrome complicating adalimumab therapy in Crohn's disease. World J Gastroenterol 2009;15:4449-52.
Lupu I, Voiculescu VM, Bacalbasa N, Prie BE, Cojocaru I, Giurcaneanu C, et al.
Cutaneous adverse reactions specific to epidermal growth factor receptor inhibitors. J Med Life 2015;8:57-61.
Anforth R, Carlos G, Clements A, Kefford R, Fernandez-Peñas P. Cutaneous adverse events in patients treated with BRAF inhibitor-based therapies for metastatic melanoma for longer than 52 weeks. Br J Dermatol 2015;172:239-43.
Gençler B, Gönül M. Cutaneous side effects of BRAF inhibitors in advanced melanoma: Review of the literature. Dermatol Res Pract 2016;2016:5361569.
What is new?
The presentation of cutaneous adverse drug reaction is not always typical. The clinician should therefore be familiar with unusual and rare presentations as well.
A possibility of paradoxical drug reactions should be kept in mind when a primary disease gets worsened with a drug used to treat that disease; the examples include immune reconstitution inflammatory syndrome (IRIS) with antiretroviral therapy and induction and/or worsening of psoriasis by TNF-alpha inhibitors.
- Many drugs considered safe may cause adverse drug reactions, many of which may be serious.
- Many newer and targeted agents often believed to be safe, can have bizzare and unusual presentation of adverse drug reactions.
[Table 1], [Table 2], [Table 3], [Table 4]
| Article Access Statistics|
| Viewed||4126 |
| Printed||59 |
| Emailed||0 |
| PDF Downloaded||169 |
| Comments ||[Add] |