Prurigo Nodularis in a Patient With Primary B‐Cell Immunodeficiency Successfully Treated With Low‐Dose Methotrexate: A Case Report

ABSTRACT

Prurigo nodularis is a chronic pruritic condition that leads to a vicious itch‐scratch cycle, which can significantly impair quality of life. Low‐dose methotrexate is an effective option for patients with chronic nodular prurigo not responding to topical therapy, offering a favorable safety profile and improving their quality of life.

Abbreviations

IL

Interleukin

IVIg

Intravenous immunoglobulin

MTX

Methotrexate

PN

Prurigo Nodularis

QOL

Quality of Life

1. Introduction

Prurigo nodularis (PN) is a recalcitrant chronic pruritic disorder involving the interaction of the cutaneous, immune, and nervous systems, which lead to the vicious cycle of itch‐scratch [1].

The first aim of the treatment is to break this cycle; therefore, multiple therapies targeting the multimodal pathophysiology of PN can be used to achieve a clinical improvement including topical corticosteroid, topical calcineurin inhibitors, in addition to the systemic treatments such as antihistamine, antidepressant, and immunosuppressant that might be considered [2].

We present a case of a 12‐year‐old male patient with primary B‐cell immunodeficiency, suffering from chronic prurigo nodularis, that was successfully treated with a low dose of methotrexate.

2. Case History/Examination

A 12‐year‐old male patient, known to have primary B‐cell immunodeficiency with hypogammaglobulinemia, presented for excoriated nodular lesions on the upper and lower extremities and back of 3‐year duration.

The lesions are highly pruritic, significantly affecting his quality of life (Figure 1). He tried multiple treatments including topical clobetasol propionate 0.05% daily for 2 months, systemic prednisolone 15 mg daily for 2 weeks, and emollient daily, without improvement.

FIGURE 1.

On presentation, before methotrexate therapy: Multiple erythematous excoriated papules and nodules on the upper and lower extremities.

Note that he was diagnosed with primary B‐cell immunodeficiency during infancy, by low immunoglobulin levels, after having recurrent pulmonary infections. He has been on Intravenous immunoglobulin (IVIg) injections every 3 weeks since the age of 2.

3. Methods (Differential Diagnosis, Investigations, and Treatment)

Histopathology showed psoriasiform epidermal acanthosis with hypergranulosis, prominent hyperkeratosis, and focal parakeratosis containing plasma. Focus of pseudoepitheliomatous hyperplasia with irregular acanthosis exhibiting bulbous rete ridges extending to the dermis. Fibrin deposition in the papillary dermis, suggestive of focal excoriation/rubbing. Superficial dermal perivascular mild lymphocytic inflammatory cell infiltrate with numerous eosinophils admixed. Appearances are compatible with prurigo nodularis. (Figure 2).

FIGURE 2.

Skin biopsy from right arm nodule. Large arrow: hyperkeratosis; small arrow: epidermal acanthosis with hypergranulosis; arrowhead: bulbous rete ridge.

Dupilumab therapy was our first plan of treatment; however, it was not financially affordable for the family. Due to the poor quality of life of the patient and constant pruritus, and after getting clearance from his pediatric hematologist, he was started on a low dose of oral MTX 12.5 mg once per week with folic acid 5 mg per day for 3 days following the MTX dose. In addition, he received a short course of high‐potency topical steroid (clobetasol propionate 0.05%) daily for 3 weeks and daily emollient.

4. Conclusion and Results (Outcome and Follow‐Up)

After 6 weeks of treatment, there was almost complete resolution of pruritus, disappearance of the nodule, in addition to the dramatic improvement in his QOL (Figure 3).

FIGURE 3.

6 weeks post MTX therapy, resolution of the lesions on the upper and lower extremities and posterior gluteal area with post‐inflammatory changes.

5. Discussion

PN is a chronic inflammatory cutaneous disorder characterized by pruritus as its hallmark feature, lasting longer than 6 weeks, as well as the development of hyperkeratotic papular/nodular lesions, ranging from very few to hundreds of lesions [3]. This disease is associated with considerable symptom burden impacting negatively the QOL, resulting in impaired sleep and higher healthcare utilization [4].

MTX is a folic acid antagonist with anti‐inflammatory, anti‐proliferative, and immunosuppressive actions. It has been traditionally used in dermatology for over 50 years, with multiple indications including psoriasis, atopic dermatitis, mycosis fungoides, vesiculobullous diseases, and many autoimmune dermatologic diseases [5].

The efficacy of low‐dose MTX in treating PN was mentioned in multiple studies. In a recent study by Huyen T et al. found that the administration of 10 mg of methotrexate weekly for patients with PN significantly reduces the number of active lesions compared to the control group at 8 and 12 post‐treatments [6].

In another study by Klejtman T et al. on 39 patients with a previous failure of conventional treatment of PN treated with MTX, the median weekly dose was 15 mg; this dose was effective both on subjective pruritus and on objective cutaneous lesions in patients with chronic refractory Prurigo, in addition to providing long‐lasting effects and a minimal side profile [7].

As for the mechanism of action, MTX at low doses leads to an increase in both intracellular and extracellular adenosine levels, resulting in anti‐inflammatory effects through mechanisms distinct from its role as a folate antagonist [8]. This will result in many actions, including suppression of the oxidative burst in neutrophils and monocytes, inhibition of leukocyte chemotaxis, regulation of cytokine secretion by monocytes and macrophages, including tumor necrosis factor‐alpha (TNF‐α), IL‐10, and IL‐12. These combined effects contribute to methotrexate's robust anti‐inflammatory properties in low‐dose therapeutic regimens [9].

Low‐dose MTX is well‐tolerated; side effects include gastrointestinal problems, such as nausea, aphthous ulcer, mild elevations in hepatic transaminases, and hematologic abnormalities, particularly mаcrocytоѕis [10]. The concurrent use of folic acid during MTX therapy was associated with a reduced risk of any side effects [11].

Our patient experienced remarkable improvement with weekly oral methotrexate (MTX) at a dose of 12.5 mg. However, in the setting of B‐cell immunodeficiency and associated hypogammaglobulinemia, there is a concern about an increased risk of infection. On the other hand, considering his poor QOL, frequent school absences, and inability to sleep at night, along with regular IVIg therapy every three weeks, we decided to proceed with MTX treatment.

Finally, a systemic review by Ibrahim A et al. revealed that MTX therapy was not associated with an increased risk of serious infections, including pulmonary infection, in all inflammatory rheumatic diseases (psoriasis, inflammatory bowel disease) [12].

6. Conclusion

In conclusion, an understanding of the benefit–risk and cost‐effectiveness of the treatment should be taken into consideration, as in our patient. Low‐dose MTX is effective with a mild side effect profile and can be used safely as an option in the treatment of PN.

Author Contributions

Hamad El Hajj: conceptualization, investigation, writing – original draft, writing – review and editing. Dima Jeha: investigation, writing – original draft. Jennifer Abi Younis: conceptualization, investigation, validation. Peter Noun: conceptualization, investigation, validation. Maya Habre: conceptualization, investigation, supervision, writing – review and editing.

Ethics Statement

Written informed consent was taken from the patient.

Conflicts of Interest

The authors declare no conflicts of interest.

El Hajj H., Jeha D., Abi Younis J., Noun P., and Habre M., “Prurigo Nodularis in a Patient With Primary B‐Cell Immunodeficiency Successfully Treated With Low‐Dose Methotrexate: A Case Report,” Clinical Case Reports 13, no. 7 (2025): e70605, 10.1002/ccr3.70605.

Data Availability Statement

The data used to support the findings of this study are included within the article.Written informed consent was obtained from patient to publish this report.