Psoriatic Onycho-Pachydermo Periostitis: Clinical Implications and Response to Therapy

Dear Editor, Psoriatic onycho-pachydermo periostitis (POPP) is an uncommon entity that was first described in 1989 by Fournié et al.[1] With 38 cases reported to date, POPP is characterized by a triad of nail involvement, soft tissue swelling, and radiological evidence of periostitis.[2] Though considered a variant of psoriatic arthritis (PsA), POPP can also be considered a distinct form of nail psoriasis, reinforcing its position as the link between psoriasis and PsA. We present an interesting case of nail psoriasis in an adult female, evolving as POPP. This case also underscores the therapeutic efficacy of tumor necrosis factor-alpha (TNF-α) inhibitors, highlighting their potential role as a targeted treatment option. A 38-year-old woman presented with thickening of the great toenails for 2 years, which gradually progressed to involve the rest of the toenails and a few fingernails, in the form of onycholysis and yellow discoloration. A few months later, she developed painful swelling and erythema of the distal toes, significantly impairing ambulation and daily activities. She had no prior history of similar lesions. On examination, affected toenails were thickened with surrounding erythema. There was distal swelling of the great toes, giving them a “drumstick appearance” [Figure 1a]. Affected fingernails showed longitudinal ridging, pitting, onycholysis, and nail plate thickening. Onychoscopy of toenails showed distal onycholysis with a regular edge and proximal erythema [Figure 2a]; while onychoscopy of fingernails showed distal onycholysis with an irregular proximal margin and prominent onychoschizia [Figure 2b].Figure 1: (a) Psoriatic onycho-pachydermo periostitis showing swelling of the terminal phalanx with onychodystrophy, subungual thickening, and periungual erythema involving toenails. A characteristic “drumstick appearance” of the digits can be appreciated. (b) Significant decrease in swelling and erythema seen in the patient after treatment with etanerceptFigure 2: (a) Onychoscopy of the great toenail shows distal onycholysis with a regular proximal margin and subungual hyperkeratosis. Prominent onychorrhexis can be seen (b) Onychoscopy of the fingernail shows distal onycholysis with an irregular proximal margin, prominent onychoschizia, and scaling over proximal and lateral nail folds (DermLite DL4, polarized mode, 10×)On investigating further, high-resolution ultrasonography revealed thickened, irregular nail plates with enthesitis and enthesophytes. Magnetic resonance imaging (MRI) showed marrow edema in the distal phalanges of affected toes with subcutaneous edema in bilateral great toes, without any distal interphalangeal joint (DIP) joint erosions [Figure 3a]. Nail bed biopsy showed matrix hyperkeratosis, parakeratosis, and significant neutrophilic infiltrate [Figure 3b].Figure 3: (a) Magnetic resonance imaging of the great toe showing bone marrow edema (yellow arrow). (b) Histology showing hyperkeratosis with parakeratosis (green asterisk) of the nail matrix with dense neutrophilic infiltration (yellow asterisk) (Hematoxylin and eosin 100×)Based on the above findings, a diagnosis of POPP was established. The patient was initiated on methotrexate 15 mg weekly, reaching a total cumulative dose of 632.5 mg. She was in addition treated with topical potent steroid (clobetasol propionate 0.05%) and calcipotriol (0.005%) ointment. However, there was minimal clinical improvement. Given the persistent disease activity, methotrexate was tapered and discontinued and etanercept was introduced at an initial dose of 50 mg thrice/week subcutaneous (SC) for 3 weeks, followed by 50 mg twice/week SC for 3 months. A marked improvement was seen in affected digits over the first two months. Regular follow-up on continued etanercept therapy of 50 mg/week SC demonstrated resolution of nail changes over the subsequent 6 months [Figure 1b]. POPP most commonly affects the great toes, although any number of fingers and toes may be involved.[1] As per a literature review, great toes were involved in 77.4% patients, with 45.1% having involvement of the DIP joint, unlike our case, where no joint changes were seen.[3] The proposed diagnostic criteria for POPP emphasize(s) the classical triad of nail involvement, painful swelling of the surrounding soft tissue, and osseous changes (acral solid periosteal reaction and osseous compaction, producing an “ivory phalanx,” without involvement of DIP).[2] The pathogenesis is, however, unclear. A distinct region of nail bed mesenchyme located beneath the matrix, and having specialized “onychofibroblasts,” is thought to be the link between the concurrent inflammation of subungual tissue and distal phalanx, producing the distinctive bone edema characteristic of POPP.[2] The superficial lamina of the digital extensor tendon attaches to the nail root and matrix, thus explaining the concurrent and universal nail matrix involvement in POPP.[3,4] Differential diagnoses include PsA, Synovitis Acne Pustulosis Hyperostosis Osteitis (SAPHO) syndrome, dactylitis, onychomycosis, other causes of periostitis, such as trauma, and inflammatory arthropathies, such as rheumatoid arthritis (RA). The classic drumstick appearance with prominent soft tissue thickening points towards POPP instead of PsA. Nail bed involvement, absence of concomitant acne, along with predominant peripheral joint involvement (not axial), helped differentiate from SAPHO. While marrow edema and periostitis are features of both POPP and dactylitis, an absence of tenosynovitis and peritendinous inflammation favored POPP. Thus, MRI is the investigation of choice in suspected cases and helps in diagnosis as well as in ruling out close differentials. Nail histopathology helped rule out onychomycosis. RA typically presents with symmetrical polyarthritis, as opposed to the DIP predominant pattern of inflammation seen in our case.[5] The long-term prognosis of POPP is often unfavorable, and treatment is difficult, with no clearly defined treatment protocols. The severity of symptoms justifies systemic interventions to improve quality of life. Onychodystrophy has been seen to be the most resistant component, as was seen in our patient as well, who responded suboptimally to methotrexate.[5] As per our comprehensive literature review, methotrexate has been used in 17 out of 38 patients [Supplementary Table 1]; however, response was highly variable, with six showing marked improvement, three responding only partially, and eight reporting no improvement. Anecdotal evidence regarding the use of sulfasalazine, leflunomide, retinoids, and cyclosporine exists, though without much success. However, biologics such as TNF-α antagonists and interleukin-17 inhibitors have reported higher efficacy.[3] This was reflected in our patient with a prolonged disease, achieving significant improvement with etanercept. In conclusion, awareness regarding the distinctive presentation of POPP is crucial, as it significantly impacts patients’ quality of life. With the advent of newer biologics, therapeutic success has greatly improved, underscoring the need for focused research and refined treatment strategies for this rare entity. Declaration of patient consent The authors certify that they have obtained all appropriate patient consent forms. In the form the patient has given her consent for her images and other clinical information to be reported in the journal. The patient understands that her name and initials will not be published and due efforts will be made to conceal her identity, but anonymity cannot be guaranteed. Financial support and sponsorship Nil. Conflicts of interest One of the authors is a member of the editorial board of the journal. The manuscript was subject to journal’s standard procedure and peer review was held independently of the editor or their research group. Use of artificial intelligence (AI) The preparation of this manuscript was carried out entirely by the authors without the use of artificial intelligence technologies.Supplementary Table 1: Review of various treatment modalities used in the management of Psoriatic Onycho-pachydermo Periosteitis (POPP) as per existing literature