Case Report - (2019) Volume 4, Issue 1
Porokeratosis is a pre-malignant skin condition with a great variety of types and clinical presentation. Delay diagnosis and treatment is common as the asymptomatic lesion may easily un-noticed by the attended especially in a hectic clinic setting. Untreated, large porokeratosis may develop into squamous cell carcinoma and metastasize especially in the chronic immunosuppressed. We reported a case of a female middle-aged lady who presented with a thirty years history of porokeratosis of Mebelli satisfactorily managed by topical imiquimod after sixteen weeks duration with complete clearance. Wounds and ulcerations are a significant downtime during therapy.
Keywords: Porokeratosis of Mibelli; Diagnosis; Topical imiquimod cream
Porokeratosis of Mibelli (PM) is a rare cutaneous disorder of epidermal keratinization, morphologically consisting of asymptomatic annular plaques with raised horny edge and central atrophy. The characteristic histological feature is the presence of cornoid lamella which is a clonal expansion of atypical keratinocyte in the skin epidermis with abnormal terminal differentiation [1,2]. The exact aetiology and pathogenesis are unknown. Somatic gene mutation, exposures to ultraviolet light, and chronic immunosuppression are suggested associations. Very few large case study series was reported in the literatures. Randomized clinical trials are lacking in providing evidenced based cost-effective treatment of the condition. We reported a case of PM in a middle-aged woman presented with a prolonged history of PM satisfactorily managed by 5% Topical Imiquimod cream. The importance of nursing and wound care during the treatment period will be discussed and emphasized.
A 58 year-old female visited our skin clinic on 11 July 2018 consulting an enlarging erythematous plaque over right upper arm which she reported to have existed for thirty years. She denied any symptoms. The reason she sought medical attention is because the plaque has been growing in size and colours intensified. Increasing scaliness with elevation of horny borders were also noted. She suffered from a long history of diabetes mellitus and hyperlipidaemia controlled by oral metformin and rosuvastatin. She has no history of malignancy, liver or renal diseases and immunosuppressive therapy. She reported to be a very active swimmer at youth. On examination, a 4.5 cm × 5.0 cm irregular annular skin plaque is evident over the right upper arm. The plaque has a raised erythematous hyperkeratotic edge bordering the whole lesion; there is central atrophy. At this juncture, the clinical differential diagnosis was discoid lupus erythematosus, lichen planus, necrobiosis lipoidica, lipogranuloma annulare, chronic vasculitis, chronic fungal infection, chronic psoriasis, discoid eczema, lichen simplex chronicus and skin malignancy. A diagnostic skin biopsy was performed with patient consent.
The histology reported sections of biopsied skin covered with thick orthokeratotic and parakeratotic scales. Multiple cornoid lamellas are present composed of thin column of parakeratotic cells with an absent or decreased underlying granular zone and vacuolated or dyskeratotic cells in the spinous layer. The epidermis is atrophic. There are dilated capillaries or telangiectasia in the underlying papillary dermis. Mild superficial perivascular lymphocytic infiltrate is seen. There is no necrobiotic granuloma in the dermis. No interface dermatitis or vasculitis. PAS stain for fungal elements is negative (Figure 1). The histological diagnosis is porokeratosis. Hence, a clinical diagnosis of PM was made supported by a pathological confirmation. The patient was carefully explained and counselled about the nature and course of the condition; particularly emphasizing the pre-malignant nature of PM. Sun avoidance of the skin with adequate cover and sunscreen are advised. The patient was also told that minimal trauma may aggregate the lesion. She was promptly referred to the public dermatology and oncology centre for further management. Unfortunately, since there is a long waiting time and the appointment was made two years later; the patient requested management in a private setting. The huge size of the lesion made surgical management like excision, cryotherapy and electrodessication difficult and unacceptable to the patient. She was managed with topical immunosuppressant of imiquimod cream for duration of sixteen weeks under supervision.
Figure 1: Histopathological slides from the case showed porokeratosis featuring columns or stacks of parakeratosis in the cornified layer and telangiectasia in the papillary dermis. The characteristic feature of cornoid lamella is indicated by blue arrow.
She responded well in the initial four weeks period with partial clearance of the lesion. She did not complain of any flu like symptoms and discomfort due to the systemic side effects of interferon administration. However, after this period, there was a significant erosions and superficial ulcerations in the rest of the lesion secondary to the applications of imiquimod cream. Clinically this required careful explanation, reassurance that the ulcers are not malignant, regular nursing attendance, meticulous wound care and dressings. During occasions, applications of the topical imiquimod have to be delayed because of consequential oozing and wound formations which inevitably required debridement, cleansing and dressings. Wound nurse treatment and care was performed on alternate day. Nonetheless, after a total sixteen weeks alternate day immunosuppressant application regimes, the lesion was virtually completely disappeared with mild to moderate post inflammatory hyperpigmentation (Figure 2). The overall patient’s compliance and acceptance to the therapy is reported to be good and satisfactory.
Figure 2: Serial pictures taken in our case of PM during the sixteen weeks topical Imiquimod treatment showing initial good rapid response followed by erosions, ulcerations and wounds formation over treated areas until complete clearance.
To date; a number of variants of porokeratosis were reported in the literature. Table 1 showed the major and minor types of porokeratosis reported and their documented treatment options [3]. PM; also known as classical porokeratosis; was reported to be one of the commonest forms of porokeratosis. In some review, up to one third of porokeratosis are PM [4]. Known precipitating factors are excessive sun exposure, trauma, burnt, immunosuppression, diabetes mellitus, liver diseases, malignancy, bone marrow, heart and renal transplantation, HIV infection and topical corticosteroid therapy [5-10]. Male is more often affected than female [3,4]. Asymptomatic small plaque like lesion usually started at early childhood and teenage progressively enlarged in usually sun-exposed areas like the extremities. It is important for the attending doctors paying vigilant attention to this unusual non-pruritic lesion at an early stage to prevent pre-malignant progression.
| Porokeratosis | Treatment | ||
|---|---|---|---|
| Surgical | Medical | ||
| Common Forms | Classic porokeratosis of Mibelli | Q-switch Ruby laser | 5-fluorouracil/Topical Imiquimod/Ingenol mebutate |
| Disseminated superficial actinic porokeratosis | Cryotherapy/Electrodessication/1927 nm thulium fractional laser/Q-switch ruby laser/Photodynamic therapy | 5-fluorouracil/Calcipotriol/tacalcitol/Systemic isotretinoin; 20 mg daily | |
| Disseminated superficial nonactinic porokeratosis | Nd: YAG laser | 5-fluorouracil/Diclofenac gel (3%) | |
| Linear porokeratosis | Dermabrasion/585 nm pulsed dye laser/Photodynamic therapy | 5-fluorouracil/Tacrolimus (0.1%) | |
| Porokeratosis palmaris et plantaris disseminata | Cryotherapy/Electrodessication | 5-fluorouracil | |
| Punctate porokeratosis | - | 5-fluorouracil | |
| Uncommon Forms | Porokeratosis ptychotropica | - | 5-fluorouracil |
| Porkeratoma (porokeratoma acanthoma) | - | 5-fluorouracil | |
| Porokeratotic adnexal ostial nevus | - | 5-fluorouracil | |
| Pruritic popular porokeratosis | - | 5-fluorouracil | |
| Pigmented porokeratosis | - | 5-fluorouracil | |
| Punctate follicular porokeratosis | - | 5-fluorouracil | |
Table 1: Types and variants of Porokeratosis and their documented treatment [3]. The preferred treatment is in italics.
All porokeratosis share the hallmark pathological features of cornoid lamellation [1,2]. Cornoid lamella represents a genetic faulty terminal differentiation of the epidermal keratinocyte during its maturation. Histologically, this resulted in a densely packed narrow column of parakeratotic cells amidst in a grove of epidermis filled with keratin. The parakeratotic column may angle through the epidermal follicular structure like the eccrine glands giving the false impression that the lesion is arise from the later; porokeratosis is in fact; a misnomer of hyperproliferation of the eccrine glands. Recently, the aberrant keratinocytes situated in the cornoid lamella have been shown to have an immunohistochemical staining patterns similar to premalignant solar keratosis and malignant squamous cell carcinoma [11-14]. However, the immunopathological mechanism of the transcription and translation to malignancy is not fully evaluated.
Various surgical treatment modalities have been used to manage porokeratosis. However, in our case of PM, surgical treatment especially excision is inappropriate; firstly, excision is usually indicated for lesion which have already transformed malignant; secondary, the sheer size of the lesion may make this treatment complicated and unacceptable to the patient. Cryotherapy and electrodessication are only preferred for smaller lesion like the disseminated porokeratosis and the end point maybe difficult to assess. Various lasers used lacked overwhelming convincing evidence of effectiveness. As a medical treatment, since 5-flurouracil cream is not available, immunomodulatory therapy consisted of topical imiquimod cream was considered and used with patient consent. The reasons we choose this treatment in our case are scientifically, there are at least two documented literature reports, although not double-blind clinical trial; suggesting the effectiveness of this treatment modalities [15-17]. In addition, topical imiquimod is a convenient, cost-effective localized therapy readily acceptable by the patient. This will increase the compliance of patients to the treatment of this chronic lesion. Last, but not the least, for dermatologist, using immunomodulatory agents like topical imiquimod is not new and most of us have experience in using it in managing premalignant skin condition like premalignant genital and anal condylomata accuminata. Nevertheless, our case has shown that topical imiquimod may have serious downtime and adverse effects, namely significant skin erosions, ulcerations and wound formation which needs careful wound care and nursing attention. The latter suggested the importance of team care with mandatory nursing support having an expertise on wound care and dressing. This should be particularly highlighted because the ulcerations and erosions may make the patient suffered from this condition misbelieved that the treatment had turned the lesion malignant. Careful explanation and a good nursing, doctor patient relationship is essential and fundamental in the successful management of giant PM. The action and mechanism of Imiquimod in eradicating PM is unknown though it may induce interferon- and cytokines secretion. Newer therapeutic agent like ingenol mebutate has been reported to be a probable effective treatment option of PM [18].
In sum, we reported a case of histologically confirmed large, longstanding PM over right upper arm satisfactorily managed and treated by topical imiquimod cream for duration of 16 weeks. This treatment is cost-effective especially in a specialist private clinic setting and acceptable to patient. The erosions, ulcerations and wounds formation secondary to the topical imiquimod is a practical concern and are the main drawbacks and adverse effects of the treatment. Good communication with the patient, specialist nurses with a good knowledge and expertise in wound care and dressings are essential and provide adjuvant support to the successful management of this chronic condition.
