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 Table of Contents  
CASE REPORT
Year : 2019  |  Volume : 5  |  Issue : 1  |  Page : 42-45

“PRIDE” Complex: A Report of Two Cases


Department of Dermatology, Venereology and Leprosy, Government Medical College, Nagpur, Maharashtra, India

Date of Web Publication22-Jul-2019

Correspondence Address:
Dr. Bhagyashree Babanrao Supekar
Department of Dermatology, Venereology and Leprosy, Government Medical College, Nagpur, Maharashtra
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijdd.ijdd_8_19

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  Abstract 


Epidermal growth factor receptor inhibitors are currently widely used for the treatment of nonsmall cell lung cancer and head-and-neck malignancy. These are associated with constellation of cutaneous reactions termed as PRIDE complex which comprises papulopustules and/or paronychia, regulatory abnormalities of hair growth, itching, and dryness. We report two cases of PRIDE complex, diagnosed clinically and histopathologically in patients of nonsmall cell carcinoma of the lung being treated with erlotinib and gefitinib.

Keywords: Epidermal growth factor receptor, papulopustulosis, PRIDE complex


How to cite this article:
Agrawal SK, Supekar BB, Wankhade V, Singh RP. “PRIDE” Complex: A Report of Two Cases. Indian J Drugs Dermatol 2019;5:42-5

How to cite this URL:
Agrawal SK, Supekar BB, Wankhade V, Singh RP. “PRIDE” Complex: A Report of Two Cases. Indian J Drugs Dermatol [serial online] 2019 [cited 2019 Aug 21];5:42-5. Available from: http://www.ijdd.in/text.asp?2019/5/1/42/263104




  Introduction Top


Epidermal growth factor receptor (EGFR), a transmembrane glycoprotein, belongs to tyrosine kinase receptor family.[1] Epithelial tissues and hair follicles physiologically express EGFR which is overexpressed in many tumors.[1] Monoclonal antibodies against the EGFR, e.g., cetuximab, panitumumab, milatuzumab, or EGFR tyrosine kinase inhibitors, e.g., gefitinib, erlotinib are generally well tolerated and do not have the severe systemic side effects.[2],[3] EGFR inhibitors have the ability to target cancer cells; therefore, they are currently used for treating advanced malignancy. These are commonly associated with dermatological side effects consisting of acneiform eruptions, xerosis, eczema, paronychia, and changes in the hair and nails.[3],[4] The acronym “PRIDE” is used for constellation of cutaneous side effects which include papulopustules and/or paronychia, regulatory abnormalities of hair growth, itching, and dryness due to EGFR inhibition.[5]


  Case Report Top


A 53-year-old male, diagnosed case of nonsmall cell lung cancer on treatment with gefitinib for 2½ months, was referred from radiotherapy and chemotherapy department for multiple pruritic reddish raised lesions on the face, trunk, and extremities for 1 month. On examination, there were multiple discrete follicular, erythematous papules and pustules over the face, upper chest, upper arm, abdomen, and thigh [Figure 1]a, [Figure 1]b, [Figure 1]c. Xerosis was present over the abdomen, thighs, and legs [Figure 1]d. There was diffuse hair loss over the entire scalp. Palms, soles, nails, and mucosa were not involved. Systemic examination revealed no abnormality. Histopathology from pustules over abdomen revealed subcorneal clefting in the epidermis with perivascular and periadnexal mixed inflammatory infiltrate comprising neutrophils and lymphocytes in the dermis [Figure 2]a and [Figure 2]b.
Figure 1: (a-d) Case 1 – Multiple discrete follicular, erythematous papules, and pustules over the face, upper chest, upper arm, abdomen, and thigh (a-c). Xerosis over the trunk (d)

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Figure 2: (a-d) Histopathology from pustules over abdomen revealed subcorneal clefting in the epidermis and perivascular and periadnexal mixed inflammatory infiltrate comprising neutrophils and lymphocytes in the dermis (a and b). Histopathology from pustules over the left thigh revealed subcorneal and intraepidermal abscess consisting of mainly neutrophil and perivascular and periadnexal mixed inflammatory infiltrate and dermal edema in the dermis (c and d)

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The second case was a 47-year-old male, diagnosed case of nonsmall cell lung cancer treated with eight cycles of pemetrexed in 9 months duration and two cycles of erlotinib for the last 2 months. He presented with multiple itchy reddish-raised lesions over the lower limbs for 1½ month. On examination, there were multiple erythematous papules, pustules and nodules over the trunk, and bilateral lower limbs [Figure 3]a, [Figure 3]b, [Figure 3]c. Xerosis on extremities and trunk was seen. Examination of the palms, soles, scalp, nails, and mucosa was normal. Systemic examination revealed no abnormality. Histopathology from pustules over the left thigh revealed subcorneal, and intraepidermal abscess consisting mainly neutrophils, perivascular and periadnexal mixed inflammatory infiltrate, and edema in the upper dermis [Figure 2]c and [Figure 2]d.
Figure 3: (a-c) Case 2 – Multiple erythematous papules, pustules, and nodules over the bilateral lower limbs

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Routine investigations, including complete hemogram, serum biochemistry, and urinalysis of both patients, were within normal limits. Based on the clinical features and histopathological examination, a diagnosis of PRIDE complex was made in both cases. On the basis of National Cancer Institute-Common Terminology Criteria for Adverse Events v 4.02 Grading of PRIDE complex,[6] our first case diagnosed as Grade 2 and the second case as Grade 1 type of PRIDE complex [Table 1]. Since the clinical features were mild, so treatment of both the patients was continued with EGFR inhibitor. Both the patients were treated with benzoyl peroxide 2.5% wash and doxycycline 100 mg BD for 2 weeks. Xerosis was treated with regular application of emollients. Both patients showed excellent response in the form of resolution of all lesions within 2 weeks of treatment [Figure 4]a, [Figure 4]b, [Figure 4]c, [Figure 4]d. Pre treatment and post treatment comparative photos of case 2 can be seen in [Figure 5]a, [Figure 5]b, [Figure 5]c, [Figure 5]b. No improvement in hair loss was observed in the first patient.
Table 1: National Cancer Institute - Common Terminology Criteria For Adverse Events v 4.02 Grading of PRIDE complex

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Figure 4: (a-d) Case 1 – Excellent response in the form of resolution of all lesions in Case 1 within 2 weeks of treatment

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Figure 5: (a and b) Case 2 – Multiple erythematous papules, pustules, and nodules over the bilateral lower limbs (pretreatment a) and posttreatment (b)

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  Discussion Top


EGFR are used for malignancies which include metastatic nonsmall cell lung cancer, colorectal cancer, pancreatic cancer, and squamous cell carcinoma of the head and neck. Corneocytes of the basal layer, sweat glands, and hair follicles largely express EGFR.[1],[7] Normal functions of the skin are inhibited which causes cutaneous adverse effects.[1],[6] Incidence of these cutaneous adverse events from EGFR inhibitors was found to be 68.7%–80% of patients.[3],[8] Various precipitating factors for these cutaneous adverse effects are sun exposure, concomitant radiotherapy, and inadequate moisture levels in the skin.[9]

Chanprapaph et al. reported the onset of adverse effect ranged from 8 days to 15 weeks after treatment with EGFR inhibitors and the earliest cutaneous adverse event was papulopustular eruption (PPE), for which the median latent period was 13 days (range 8–25 days).[3] The most common adverse event is xerosis, followed by PPE.[3] Less common adverse events reported were maculopapular rash, mucositis, paronychia, and trichomegaly of the eyelashes, telangiectasia, and hyperpigmentation.[4],[7],[8],[9],[10] Severe xerosis with mucosal involvement can sometimes lead to sicca-like syndrome.[10] Cutaneous adverse events have been observed with all agents that target EGFR and therefore considered a class-specific effect, and the frequency and severity of skin rashes are dose dependent.[10] Some authors stated that the presence and intensity of a PPE have a positive correlation with the effectiveness of the therapy, suggesting a gradual increase in dose until a severe PPE is produced(“dose to rash).[11] The acronym “PRIDE” is used for constellation of cutaneous side effects which include papulopustules and/or paronychia, regulatory abnormalities of hair growth, itching, and dryness due to EGFR inhibition. Pathogenesis and treatment of PRIDE complex is depicted in [Table 2].[4],[8],[9],[12]
Table 2: Pathogenesis and treatment of PRIDE complex

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The PPE s usually arises a few days after treatment with the EGFR inhibitor, to reach a maximum after 2–3 weeks. More rarely (11%), the rash occurs in a delayed fashion after the first 3 weeks of treatment with cetuximab.[2] These lesions are more pruritic, erythematous, and more inflammatory as compared to other drug-induced acneiform eruptions.[2],[3],[9] The eruption is more or less confined to the seborrheic areas such as the face, neck and retroauricular area, the shoulders, V-shaped area of the upper trunk, and the scalp.[13] The lower parts of the back, the abdomen, the buttocks, and even the arms and legs can be rarely involved as well, whereas the palms and soles are spared.[3],[11],[13] Incidence of PPE was reported to be 27.3%–86% from previous studies.[3],[14] The classical presentation of PPE is inflamed papules or pustules with hair at the center.[3] In histopathology, acneiform lesions show a picture of a florid superficial suppurative folliculitis, i.e., neutrophilic folliculitis and perifolliculitis.[10],[15] PPEs and xerosis were more commonly reported with erlotinib than with gefitinib.[3],[8]

Our first case had PPE s in the seborrheic area along with involvement of abdomen and lower limbs with xerosis in patient of nonsmall cell carcinoma of the lung, after 6 weeks of initiation of therapy with gefitinib. Our second case had similar rash over the lower limbs with less involvement of seborrheic areas with xerosis after 2 weeks of commencement of therapy with erlotinib in case of nonsmall cell carcinoma of the lung. Nail and hair abnormalities attributable to EGFR inhibitors were not observed in both of our patients. No systemic toxicities were present in both the cases. Both the patients had significant relief of symptoms after 2 weeks treatment with oral doxycycline, topical benzoyl peroxide, and emollients. Oral retinoids have same adverse effects as with EGFR inhibitor i.e., xerosis and paronychia therefore they should be avoided for treatment of papulopustular eruptions.[10] Prophylactically, the patient should be informed about cutaneous side effects and should be advised to mild soap, take quick showers with warm water, and repeated and regular use of emollients preferably all over the skin and with products containing no alcohol or perfume.[16] It is important for clinicians to be aware of this condition, as it can be treated symptomatically without discontinuation of drug. We report two cases of PRIDE complex because of its rarity in presentation.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Castillo L, Etienne-Grimaldi MC, Fischel JL, Formento P, Magné N, Milano G, et al. Pharmacological background of EGFR targeting. Ann Oncol 2004;15:1007-12.  Back to cited text no. 1
    
2.
Cunningham D, Humblet Y, Siena S, Khayat D, Bleiberg H, Santoro A, et al. Cetuximab monotherapy and cetuximab plus irinotecan in irinotecan-refractory metastatic colorectal cancer. N Engl J Med 2004;351:337-45.  Back to cited text no. 2
    
3.
Chanprapaph K, Pongcharoen P, Vachiramon V. Cutaneous adverse events of epidermal growth factor receptor inhibitors: A retrospective review of 99 cases. Indian J Dermatol Venereol Leprol 2015;81:547.  Back to cited text no. 3
[PUBMED]  [Full text]  
4.
Segaert S, Van Cutsem E. Clinical signs, pathophysiology and management of skin toxicity during therapy with epidermal growth factor receptor inhibitors. Ann Oncol 2005;16:1425-33.  Back to cited text no. 4
    
5.
Lacouture ME, Lai SE. The PRIDE (Papulopustules and/or paronychia, regulatory abnormalities of hair growth, itching, and dryness due to epidermal growth factor receptor inhibitors) syndrome. Br J Dermatol 2006;155:852-4.  Back to cited text no. 5
    
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7.
Dueland S, Sauer T, Lund-Johansen F, Ostenstad B, Tveit KM. Epidermal growth factor receptor inhibition induces trichomegaly. Acta Oncol 2003;42:345-6.  Back to cited text no. 7
    
8.
Santiago F, Gonçalo M, Reis JP, Figueiredo A. Adverse cutaneous reactions to epidermal growth factor receptor inhibitors: A study of 14 patients. An Bras Dermatol 2011;86:483-90.  Back to cited text no. 8
    
9.
Peuvrel L, Bachmeyer C, Reguiai Z, Bachet JB, André T, Bensadoun RJ, et al. Semiology of skin toxicity associated with epidermal growth factor receptor (EGFR) inhibitors. Support Care Cancer 2012;20:909-21.  Back to cited text no. 9
    
10.
Madke B, Gole P, Kumar P, Khopkar U. Dermatological side effects of epidermal growth factor receptor inhibitors: 'PRIDE' complex. Indian J Dermatol 2014;59:271-4.  Back to cited text no. 10
[PUBMED]  [Full text]  
11.
Li T, Perez-Soler R. Skin toxicities associated with epidermal growth factor receptor inhibitors. Target Oncol 2009;4:107-19.  Back to cited text no. 11
    
12.
Chanprapaph K, Vachiramon V, Rattanakaemakorn P. Epidermal growth factor receptor inhibitors: A review of cutaneous adverse events and management. Dermatol Res Pract 2014;2014:734249.  Back to cited text no. 12
    
13.
Jacot W, Bessis D, Jorda E, Ychou M, Fabbro M, Pujol JL, et al. Acneiform eruption induced by epidermal growth factor receptor inhibitors in patients with solid tumours. Br J Dermatol 2004;151:238-41.  Back to cited text no. 13
    
14.
Nakagawa K, Kudoh S, Ohe Y, Johkoh T, Ando M, Yamazaki N, et al. Postmarketing surveillance study of erlotinib in Japanese patients with non-small-cell lung cancer (NSCLC): An interim analysis of 3488 patients (POLARSTAR). J Thorac Oncol 2012;7:1296-303.  Back to cited text no. 14
    
15.
Hiatt KM, Horn TD. Cutaneous toxicities of drugs. In: Elder DE, editor. Levers Histopathology of the Skin. 10th ed. New Delhi: Wolter Klunwer (India) Pvt. Ltd.; 2009. p. 323.  Back to cited text no. 15
    
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Melosky B, Burkes R, Rayson D, Alcindor T, Shear N, Lacouture M. Management of skin rash during EGFR-targeted monoclonal antibody treatment for gastrointestinal malignancies: Canadian recommendations. Curr Oncol 2009;16:16-26.  Back to cited text no. 16
    


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]
 
 
    Tables

  [Table 1], [Table 2]



 

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