Unmasking: paronychia as the hidden face of pemphigus

Abstract

Pemphigus vulgaris (PV) is a rare, potentially life-threatening autoimmune blistering disorder primarily affecting the skin and mucous membranes. We present a unique case of delayed diagnosis in a patient with PV, initially manifesting as isolated, extensive and therapy-resistant paronychia. PV was only considered after the appearance of mucocutaneous lesions – first oral, then cutaneous – more than 1 year after symptom onset. Diagnosis was ultimately established through histopathological examination, direct immunofluorescence and serological testing. Following diagnosis, the patient received rituximab therapy, resulting in a rapid and sustained clinical remission. This case underscores the importance of considering PV in the differential diagnosis of severe, chronic and treatment-resistant paronychia. Early recognition and diagnosis are crucial for timely intervention, which can significantly improve patient outcomes. Rituximab proved highly effective in this case, aligning with current evidence supporting its use as a first-line treatment for PV. We aim to raise awareness of atypical PV presentations and stress the need for thorough evaluation of persistent, treatment-resistant paronychia to prevent delayed diagnosis.

We present a patient with severe, recurrent paronychia as the initial manifestation of pemphigus vulgaris. Due to the absence of other, more typical, mucocutaneous manifestations there was a delay in diagnosis, which is why we would like to draw attention to pemphigus as a differential diagnosis for therapy resistant paronychia.

What is already known about this topic?

• Nail changes, such as paronychia, may present as a manifestation of pemphigus vulgaris.

• Paronychia typically develops after the onset of more classical features such as mucosal or cutaneous lesions.

What does this study add?

• In our patient, paronychia was the initial clinical presentation.

• There was a significant time interval between the onset of nail involvement and the appearance of mucocutaneous symptoms.

• Pemphigus vulgaris should be included in the differential diagnosis of therapy-resistant paronychia.

Acute paronychia is a purulent inflammation of the ­periungual tissues, leading to redness, swelling and pain. Its main cause is infection by bacteria, viruses or fungi. However, other (rare) causes are not well known and are often overlooked.¹

We present a patient with recurrent, therapy-resistant paronychia involving multiple fingernails and toenails due to pemphigus vulgaris (PV). Although initially not present, the gradual appearance of typical mucocutaneous lesions eventually suggested the diagnosis, which was confirmed by histopathology and serology. PV is a well-known autoimmune intraepidermal blistering disease characterized by IgG autoantibodies targeting keratinocyte adhesion proteins (desmogleins Dsg1 and Dsg3). The binding of IgG autoantibodies to desmosomal complexes leads to a disruption in intraepidermal adhesion, which causes loss of cell–cell adhesion (acantholysis). This results in the formation of vesicles, blisters and erosions on the skin and mucous membranes. The classical presentation of PV typically involves painful erosions of the oral mucosa, which are often the initial manifestation, followed by the development of fragile, flaccid cutaneous blisters that rupture easily and result in painful erosions.² These typical clinical presentations are generally promptly recognized, accurately diagnosed and appropriately managed. However, atypical presentations – such as nonblistering variants, isolated cutaneous involvement or manifestations like paronychia – pose a diagnostic challenge, frequently leading to a delayed diagnosis.

Therefore, we hereby present this case to highlight paronychia as a recognized, yet rare and potentially ­under-reported, clinical manifestation of PV.³

Case report

A 37-year-old man presented with a 2-year history of severe paronychia, which was resistant to topical corticosteroids and disinfectants, systemic antibiotics and surgery. Sixteen months after the onset of the nail lesions he developed oral erosions, and 5 months later cutaneous erosions appeared on his trunk, folds and face. Upon clinical examination, suppurative inflammation with nail dystrophy was found on his fingers and toes Widespread buccal and lingual erosions, haemorrhagic crusts on trunk and face, and erosions on both sides of the groin were seen. Nikolsky’s sign was positive in the groin areas (Figure 1b). Initial bacterial, viral and fungal culture of the paronychia were negative. Histopathology of later- developed mucocutaneous lesions showed suprabasal cleavage and acantholysis in skin and mucosal biopsies (Figure 2). Direct immunofluorescence (DIF) on the oral biopsy demonstrated intercellular deposition of IgG in a ­honeycomb-like pattern. Enzyme-linked immunosorbent assay (ELISA) was performed for serological testing and showed elevated anti-Dsg1 and anti-Dsg3 serum levels, both at >200 U mL^–1.

Figure 1.

Initial presentation, before treatment. (a) Periungual erythema with pustules, erosions and crusts on both thumbs. (b) Erosive lesions in the right groin. (c) Intraoral erosions.

Figure 2.

(a) Intraepidermal acantholytic blister with a suprabasal cleavage plane on skin biopsy. (b) Arrows point to acantholytic cells on mucosal biopsy (haematoxylin and eosin, ×10 magnification).

Based on the clinical image, histopathology and serology, the diagnosis of PV was made. Other potential causes of therapy-resistant paronychia were excluded via a thorough investigation of the patient’s medical history – ruling out contact dermatitis, drug-induced paronychia and behavioural factors – and an extensive blood workup, including syphilis serology, serum protein electrophoresis and HIV screening, all of which yielded unremarkable results.

According to guidelines concerning PV treatment,⁴ two rituximab infusions of 1 g on day 1 and day 14 were given and methylprednisolone was added in a tapering scheme [starting dose 64 mg daily (=0.6 mg kg^–1 daily), tapered over 5 months to 4 mg daily]. All clinical manifestations, including paronychia, resolved (Figure 3). At the last follow-up, 14 weeks after rituximab administration, the patient showed persistent clinical remission.

Figure 3.

Six weeks after rituximab treatment. (a) Complete clearance of paronychia on both thumbs. (b) Healing of erosive lesions in the right groin.

Discussion

We report a case in which paronychia was the first clinical sign of PV. In the literature, nail manifestations are reported in a minority of cases of PV. A recent meta-analysis showed a pooled prevalence of nail involvement in pemphigus of 0.389 (1 in 2.57 patients had nail disease), with paronychia (185/1208 included patients) and Beau’s lines (104/1208 included patients) being the most frequent presentations.³ Although globally rare, a higher incidence of nail involvement is reported in Middle Eastern populations.⁵ In our case, the patient was of Turkish origin, which may support this suggested demographic variation.

Nail changes can precede, coincide with or follow ­mucocutaneous lesions. When following disease onset, there is a temporal variation between 0.5 months and 8 years. The number of cases with nail changes preceding disease onset is very limited.³ In a literature review by Engineer et al., 14 patients with PV with nail involvement were described and only in 3 of them did the nail disease preceded the onset of other, more typical symptoms.⁶ In our patient the interval between the onset of paronychia and the occurrence of mucocutaneous lesions was 16 months. This led to a delay in diagnosis, which highlights the importance of reporting it.

The pathogenesis of paronychia is consistent with that of mucocutaneous lesions in PV, namely acantholysis due to the binding of autoantibodies.³ In a case series of two patients with oral and digital lesions, high levels of anti-Dsg3 levels were observed. They suggest that Dsg3 might play a bigger role in nail changes in PV than Dsg1.⁵

In the literature review by Engineer et al., published in 2000, nail biopsy was reported to have been performed in 10/14 patients with PV.⁶ Suprabasal acantholysis and intercellular deposition of IgG/C3 was found, in accordance with mucocutaneous findings. Nail biopsies were not performed in this case, as the diagnosis was already confirmed through clinical presentation, histopathology, DIF and serology. Additionally, the known association between paronychia and PV, along with improvement after therapy, made further investigations unnecessary, with the aim of avoiding unnecessary procedures and patient discomfort.

Several studies have linked nail changes in pemphigus as a sign of severe PV, particularly severe oral involvement.³ This highlights the possible added value of nail examination for diagnosis, treatment selection and prognosis.

Our patient was successfully treated with rituximab and corticosteroids (in a tapering regimen). This is in line with the reported improvement in nail changes using classical treatment regimens for PV.^3,4

Rituximab, a monoclonal antibody targeting CD20 on B lymphocytes, was initially used off-label for pemphigus but has become a cornerstone in its treatment. By depleting B cells, rituximab effectively addresses autoimmune activity, shifting management from broad immunosuppression to targeted immunotherapy. It is now recommended as a first-line treatment, especially for patients with newly diagnosed pemphigus.⁷

The aim of this report is to draw attention to the fact that paronychia, even without the presence of typical mucosal or cutaneous manifestations, may be an early and rare presentation of PV. In cases of therapy-resistant paronychia, a thorough patient medical history, repeated swab cultures, additional blood tests – including ELISA – and, if necessary, biopsy are indicated. Early recognition of the disease can ensure faster, adequate treatment and an overall better prognosis.

Patient perspective (via heteroanamnesis due to language barrier): the patient reports significant improvement with minimal itching, no new blisters and less oral pain. Nails have mostly healed despite some loss. The last blister occurred in mid-September 2024.

Author contributions

Anke Lambert (Writing—original draft [lead]), Petra De Haes (Writing—review & editing [lead]), An Van Laethem (Supervision [equal], Validation [equal]), Julie Callens (Supervision [equal]), Beatrice Verhamme (Supervision [equal], Validation [equal]), Matthias Steegmans (Visualization [equal]) and Francesca Bosisio (Visualization [equal])

Funding sources

None declared.

Conflicts of interest

The authors declare no conflicts of interest.

Data availability

The data underlying this article will be shared on reasonable request to the corresponding author.

Ethics statement

This study was approved by the Research Ethics Committee UZ/KU Leuven - MP034320.

Patient consent

Written patient consent for publication was obtained.