Familial Reactive Perforating Collagenosis with Adolescence-Onset: A Rare Case Report and Literature Review

Introduction

Reactive perforating collagenosis (RPC) is a rare benign dermatosis characterized by transepidermal elimination with extruding abnormal dermal collagen through the epidermis.¹ The patient’s common clinical manifestation of RPC includes erythematous maculopapular lesions in the facial area and extremities, often covered by a central keratotic plug. Removal of the keratotic plug will reveal the crateriform shape of the erythematous papules.² The skin lesion distribution, size and depth of the keratotic plug, along with histopathological results that showed transepidermal elimination of keratin and deposition of abnormal collagen fibers are the basis for diagnosing RPC in patients.³

Based on its origin, RPC can be classified into two types: acquired (ARPC) and familial (FRPC).¹ As the terms implied, skin manifestations in ARPC are predisposed by systemic conditions, such as diabetes mellitus, neoplasms, autoimmune disorders, and liver and renal diseases; meanwhile, any of these underlying conditions are usually absent in FRPC patients.^1,4 The prevalence of FRPC in siblings and consanguineous families indicates the genetic origin of the disease.^2,4,5 Based on the number of reported cases, FRPC is the rarer form of RPC. To our knowledge, only 43 FRPC patients have been reported in the literature (see Table 1). In contrast to the adult onset of ARPC, the typical onset of FRPC is during infancy or early childhood. Concerning their symptoms, pruritus in FRPC is usually milder than ARPC.⁶ Detailed pathogenesis of FRPC is not fully understood yet; thus, therapeutic approaches are symptomatic. One of the challenges that prevented the extension of our understanding of this unique entity is its rarity; hence, the report of new FRPC cases is essential. Here, we describe a case of FRPC in an Indonesian patient with adolescence-onset. The patient’s paternal grandfather, uncle, and cousins acknowledged a history of similar symptoms. A literature review on previously published FRPC case reports was performed and summarized to discuss this unique and challenging condition comprehensively.

Table 1 Summary of Other Reported Cases of Familial Reactive Perforating Collagenosis (FRPC)

Case Presentation

A 20-year-old male was presented with generalized multiple discrete erythematous papules. Although these lesions could be identified in all regions of his body, many erythematous papules were acknowledged in specific areas, including the facial area, neck, abdominal, and extensor parts of his extremities. When carefully assessed, many of these papules were covered with central keratotic plugs. In papules where the keratotic plug was already removed, the actual crateriform shape of the lesion was identified. Each of these papules is sized 3–5 mm. The polymorphic appearance was acknowledged, suggesting a repetitive cycle of exacerbation and resolution in the patient. The latest exacerbation occurred in the last month before his visit, with the number of papules increasing. Resolved lesions from previous exacerbation could be identified by post-inflammatory hyperpigmented skin (Figure 1A–D).

Figure 1 Dermatological symptoms in our familial reactive perforating collagenosis (RPC) patient. The patient presented with generalized multiple hyperpigmented papules, particularly in (A) the facial, neck, (B) abdominal, and (C) extensor parts of the feet and (D) hands. As a repetitive cycle of resolution and exacerbation had happened multiple times, resolved lesions could be identified by the occurrence of post-inflammatory hyperpigmented macules.

The patient acknowledged the initial occurrence of the lesion seven years prior to his admission, suggesting that the age of onset is 13 years. Consanguinity was not acknowledged in the patient’s family. Nevertheless, similar clinical manifestations were acknowledged in the patient’s paternal grandfather, uncle, and cousins, suggesting an autosomal dominant inheritance pattern.

Physical examination of other body parts did not reveal anything remarkable. A routine and specific blood examination was performed to evaluate the presence of systemic diseases that could trigger exacerbation, such as diabetes mellitus, autoimmune disorders, and liver and renal diseases. Based on the blood examination results, no systemic diseases could be identified in the patient.

A punch biopsy specimen was obtained from one of the erythematous papules on the left back of his hand. Histopathological analysis based on H&E staining of the biopsy specimen revealed fibrocollagenous tissue, the keratinized epidermal layer that is covered by stratified squamous epithelium, crateriform appearance on the epidermis, and increased inflammatory lymphocytes (Figure 2A and B). Further histopathological examination by Masson trichrome staining confirmed collagen infiltration through the epidermis (Figure 2C and D). Based on the clinical and histopathological analyses, the patient was diagnosed with FRPC.

Figure 2 Histopathological results from FRPC patient. (A and B) H&E staining on the biopsy specimen identified fibrocollagenous tissue, crateriform appearance (yellow box), and enhanced inflammatory lymphocytes (green arrows). (C and D) Mason’s trichrome staining showed an infiltrated area of the epidermal layer (yellow box) with collagen fibers from the underlying dermis (green arrows). (Scale bar (A and C): 100 µm; Scale bar (B and D): 50 µm).

He was treated with topical desoximetasone 0.25% cream applied 2–3 times daily. Evaluation at one week and one month after daily topical corticosteroid application revealed a near-complete resolution of skin papules, leaving post-inflammatory hyperpigmented macules.

Discussion

The term FRPC was first coined in 1974, based on the finding of 7 patients from 2 unrelated consanguineous families.⁴ In contrast to ARPC, FRPC skin lesions are not associated with systemic disease; nonetheless, superficial trauma and atmospheric temperature have been suggested as the common predisposing factors in the exacerbation of FRPC.^3,4,8,10,13 As an inherited disease, FRPC is thought to have both autosomal recessive and autosomal dominant patterns of inheritance.^3,4 Consequently, a family history of FRPC suggests the diagnosis of FRPC. Like many other inherited diseases, the clinical manifestation of FRPC usually starts to occur during infancy or early childhood, as early as six months old.^2,16 Rarely, the onset of FRPC occurred during adolescence.^2,7

Although our patient presented at the age of 20 years old, polymorphic patterns of his skin lesions indicated that he had already undergone a repetitive cycle of resolution and exacerbation of skin lesions. The adolescence-onset of FRPC suggests the possibility of an earlier hypothesis regarding the long quiescence of FRPC.^2,13,17 Like in many other FRPC cases, comorbidity(-ies) with systemic disease was not found in our patient. This suggests that the clinical manifestation of RPC in familial cases is primarily due to the genetic alteration in the collagen-forming gene(s), leading to abnormal collagen formation through the epidermis.¹³ In many FRPC cases, superficial skin trauma and atmospheric temperature have been acknowledged as precipitating factors. Nonetheless, like in the presented case, the precipitating factors in some previously reported FRPC cases are unknown; thus, its risk of recurrence is arguably high.^{2,3,5,9,11,13,14,16}

To support the diagnosis of FRPC, a specimen from a punch biopsy on a lesion at the extensor area of the left arm was obtained and underwent histopathological analysis. Mason trichrome staining was performed on the specimen to ensure the collage content that formed the infiltrating fibrous tissue through the epidermis. Results from this staining confirmed the excessive collagen infiltration through the epidermis, supporting the diagnosis of FRPC. The histopathological characteristics identified in the specimen from our patient are similar to those suggested in previous case reports (see Table 1).

Although lesions in FRPC are self-limiting, previous reports have suggested using oral isotretinoin, topical tretinoin, steroid antibiotic cream, and emollient.^5,10,17 Previous studies described that medication with oral isotretinoin resulted in complete regression of symptoms in FRPC patients. Unfortunately, oral isotretinoin is not commercially available in our country; thus, daily application of topical desoximetasone 0.25% cream was advised, leading to a near-complete resolution that left post-inflammatory hyperpigmented macules. This result supports the use of topical corticosteroids as a potential treatment option for FRPC patients. In addition to oral and topical medications, one study suggested applying narrow-band ultraviolet B (UVB) light treatment in FRPC patients.¹¹ In our case, no further treatment was required since the results of topical corticosteroid application were satisfactory.

In addition to the clinical aspects described above, it is essential to acknowledge that this is Indonesia’s first FRPC case report. It is interesting to notice that most of the previously reported FRPC patients lived in India.^2,3,5–17 (See Table 1) Based on our literature review, only 1 study reported the prevalence of FRPC outside of India.⁴ Unfortunately, the ethnicity of these patients was not always described; nonetheless, it is tempting to speculate that ethnicity and geography might play essential roles in the pathogenesis of FRPC.

Conclusion

Based on the limited number of FRPC cases that have been reported, it is safe to conclude that FRPC is indeed a rare benign dermatosis in children. Preventing FRPC exacerbation is challenging, as precipitating factors are not always known. Furthermore, although it is self-limiting, various treatments can be applied to accelerate the resolution of FRPC and alleviate its symptoms. Future genetic studies of FRPC are required to unravel its pathophysiology.