Painful Finger Tips Secondary to Opdivo

The patient is a 65-year-old woman with metastatic lung cancer who presents for evaluation of painful fingertips.  She has also had marked axillary pruritus which she handles with Lotrisone spray. 

Her medications include metformin, two types of insulin, metoprolol, Lipitor, Lexapro, and irbesartan.  Recently, she has been started on Opdivo (nivolumab) every two weeks.  Within a few months of starting Opdivo, she developed intense axillary pruritus, and a month or so later, intensively painful fissuring of the fingertips.  Each treatment of Opdivo re-exacerbates the fingertip problem, which is unbearable. Her cancer has gone into remission and she feels well otherwise.  She especially enjoys her grandkids.

Her oncologist put her on prednisone 20 mg q.i.d. for the fingertip eczema.  Because of the patient's diabetes, her fasting blood sugars while on prednisone have gone up over 500 mg%. 

EXAMINATION:  The examination shows erosions on a few of the fingertips without erythema.  Her feet and axillae are normal.  

Clinical Photos:

We did a literature search and there are a few early reports of dermatitis with Opdivo but they do noot not affect the hands.  It may be too early to say; but given the literature on painful hands and feet related to cancer therapies this is probably a significant reaction.  

PLAN:  I would try to keep this simple and avoid the prednisone.  Start with wet soak for 20 minutes in warm water, followed by clobetasol ointment, followed by gloves (a modified Soak and Smear protocol).  We will see how she does with this.  I have the patient's permission to post her case on this site where we may get ideas and/or be of help to others with a similar problem.   There is a reference to preventing Hand Foot reactions with chemotherapy.  It seems that Celebrex (celecoxib) may be the best option. Note: Celecoxib has been reported to be associated with an increased incidence of heart attack and stroke.  It's use should not be cavalier.

References:.

1. Survey of cutaneous adverse reactions to targeted cancer therapies: value of dermatological advice. Damiani G OncoSkin working group. G Ital Dermatol Venereol. 2018 May 11. Abstract: From June to October 2012, 25 patients with cutaneous adverse reactions linked to targeted therapies were included in the study. The main prescribed drugs were cetuximab (52%) and erlotinib (20%) and the most common reactions were folliculitis/pustules (40%) and rash/erythema (40%). Hand-foot reaction syndrome was present in 8% of patients. A total of 30% of patients treated for a cutaneous reaction underwent a consultation by a dermatologist. In these patients the rate of oncologic therapy continuation without regimen modifications was higher (100%), while it was progressively lower in patients treated by oncologists (71%) or without any specific treatment (60%). Adverse reaction should be recognized by both dermatologists and oncologists and a multidisciplinary approach is mandatory.

2. Prevention strategies for chemotherapy-induced hand-foot syndrome: a systematic review and meta-analysis of prospective randomised trials.

Macedo LT, et.al. Support Care Cancer. 2014 Jun;22(6):1585-93.

Abstract

Amongst 295 studies identified, only ten met the inclusion criteria. Celecoxib prevented both moderate to severe (odds ratio [OR] 0.39, 95 % confidence interval [CI] 0.20-0.73, P = 0.003) and all-grade HFS (OR 0.47, 95 % CI 0.29-0.78, P = 0.003), whereas pyridoxine and topical urea/lactic acid formulations failed to prove efficacy. There were no proven benefits in mild HFS. The use of topical antiperspirant has not been shown to improve results, according to a single trial.

Palmoplantar Erythrodysesthesia Syndrome

Presented by Yoon Cohen, MS IV
University of New England College of Osteopathic Medicine

Abstract: 45 yo woman with a metastatic breast cancer and a painful hand/foot dermatitis.

HPI: This is a 45 yo woman who was diagnosed with a metastatic breast cancer a few years ago. She has developed "atopic dermatitis" like symptoms on her hands and feet since starting capecitabine. She has completed 5 cycles of Xeloda (capecitabine) and has had to reduce the dose because of this condition. The lesions started as dry edematous, erythematous areas on palms and soles with a tingling sensation.

O/E: The examination reveals general areas of desquamation and hyperlinearity with mild erythema on both palms. This is best shown on the first photograph. 

Clinical photographs:

Diagnosis: Palmoplantar erythrodysesthesia syndrome, hand-foot syndrome, chemotherapy-induced acral erythema

Discussion:

Chemotherapy-induced acral erythema or palmoplantar erythrodysesthesia syndrome is a well-defined reaction to some of the chemotherapeutic agents such as methotrexate, cytarabine, doxorubicin, fluorouracil, cytosine arabinoside, and bleomycin. This reaction is characterized by symmetric, well-demarcated, painful erythema of the palms and soles, which may progress to desquamation or blisters. It appears to be dose dependent, and is likely a direct toxic effect of the drug. Tingling on the palms and soles is followed in a few days by painful, symmetric, well-defined swelling and erythema [4].

Questions:

1. Please feel free to share your experiences with treatment options.

References:

1. Marini A, Hengge UR. Hand-foot syndrome with capecitabine therapy. Hautarzt. 2007 June; 58(6):532-6

Abstract: A 72-year-old patient with esophageal carcinoma developed a severe hand-foot syndrome during second-line therapy with the oral fluoropyrimidine capecitabine. We also summarize the current knowledge with regard to the hand-foot syndrome and distinguish it from palmoplantar erythrodysesthesia.

2. Degen A, Alter M, Satzger I, et al. The hand-foot-syndrome associated with medical tumor therapy- classification and management. J Dtsch Dermatol Ges. 2010 Sep; 8(9):652-61

Abstract: The hand-foot-syndrome (HFS, palmoplantar erythrodysesthesia, chemotherapy-associated acral erythema) is characterized by painful predominantly palmo-plantar lesions. The association with different chemotherapeutic agents has been known for over 20 years. More recently, HFS has been reported in association with regimens using targeted agents, in particular the multikinase inhibitors (MKI) sorafenib and sunitinib. The HFS associated with MKI has a different distribution and clinical appearance than the traditional disorder. In this review, similarities and differences between chemotherapy- and MKI-associated HFS are discussed and current recommendations for their prophylaxis and management are summarized.

3. Janusch M, Fischer M, Marsch WCh, et al. The hand-foot syndrome - a frequent secondary manifestation in antineoplastic chemotherapy. Eur J Dermatol. 2006 Sep-Oct; 16(5): 494-9

Abstract: The hand-foot syndrome (HFS) (palmoplantar erythrodysesthesia) designates acute, painful erythemas of the palms and soles of the feet caused by antineoplastic chemotherapies. The most frequent trigger substances are 5-fluoruracil and its derivates. At maximum severity, the HFS is bullous to erosive or ulcerous in character. The pathogenesis has not yet been clarified. Histologically, the HFS is characterized by a toxic keratinocyte reaction. Furthermore, there is sub-basal edema with a tendency to bullae, dilated blood and lymph capillaries and usually only mild perivascular lymphocytic infiltration. Early recognition and delineation from other differential diagnoses is prerequisite to targeted management of the disease. Depending on the severity, HFS requires dose reduction, interruption or switch in the antineoplastic chemotherapy. (You can access to the article at http://www.john-libbey-eurotext.fr/e-docs/00/04/26/D7/vers_alt/VersionPDF.pdf)

4. Habif TP. Clinical Dermatology. 5th edition. USA: Elsevier Science 2010