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A Case of Recurrent Pemphigus Foliaceus Following Noncompliance to Medication

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Pemphigus foliaceus (PF) is a rare autoimmune blistering disorder requiring consistent immunosuppressive therapy for management. A 66‐year‐old male with a history of PF presented with worsening blisters and erosions after discontinuing medication. The patient had flaccid bullae and erosions on the face, scalp, chest, and back. Histopathology confirmed PF. Treatment with oral prednisolone, azathioprine, and reinitiation of dexamethasone‐cyclophosphamide pulse (DCP) therapy led to disease remission. This case underscores the importance of adherence to immunosuppressive therapy in PF management. It also highlights the role of affordable treatment regimens in ensuring patient compliance and successful outcomes.
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Clinical Case Reports, 2024; 12:e9622
https://doi.org/10.1002/ccr3.9622
Clinical Case Reports
CASE REPORT OPEN ACCESS
A Case of Recurrent Pemphigus Foliaceus Following
Noncompliance to Medication
MasabAli1 | MuhammadHusnainAhmad2 | AliImran3 | UswaAhmad4 | RehanNaseerAhmad3
1Department of Dermatology, Punjab Medical College, Faisalabad, Pakistan | 2Department of Medicine, Tentishev Satkynbai Memorial Asian Medical
Institute, Kant, Kyrg yzstan | 3Department of Medicine, King Edward Medical University, Lahore, Pakistan | 4Department of Medicine, Aziz Fatimah
Medical and Dental College, Faisalabad, Pakistan
Correspondence: Muhammad Husnain Ahmad (husnainahmad601@gmail.com)
Received: 25 July 2024 | Revised: 11 September 2024 | Accepted: 15 October 2024
Funding: The authors received no specific funding for this work.
Keywords: autoimmune diseases| azathioprine| blisters| dexamethasone- cyclophosphamide pulse| immunosuppressive therapy| pemphigus
ABSTRACT
Pemphigus foliaceus (PF) is a rare autoimmune blistering disorder requiring consistent immunosuppressive therapy for man-
agement. A 66- year- old male with a history of PF presented with worsening blisters and erosions after discontinuing medication.
The patient had flaccid bullae and erosions on the face, scalp, chest, and back. Histopathology confirmed PF. Treatment with oral
prednisolone, azathioprine, and reinitiation of dexamethasone- cyclophosphamide pulse (DCP) therapy led to disease remission.
This case underscores the importance of adherence to immunosuppressive therapy in PF management. It also highlights the role
of affordable treatment regimens in ensuring patient compliance and successful outcomes.
JEL Classification: Gastroenterology/Hepatology, Cardiology, Endocrinology and Metabolic Disorders, Immunology
1 | Introduction
Pemphigus foliaceus (PF) is a rare autoimmune blistering dis-
order characterized by superficial blistering of the skin without
mucosal involvement [1]. It is usually diagnosed by investigations
such as histopathology after a skin biopsy, perilesional skin im-
munofluorescence, and enzyme- linked immunosorbent assay
(ELIS A) of anti- desmoglein 1 (Dsg1) antibody (Ab) [2]. Subcorneal
acantholysis is a characteristic feature which differentiates it
from pemphigus vulgaris (PV), the common pemphigus subtype,
which involves the suprabasal level [2, 3]. Effective manage-
ment typically involves immunosuppressive therapy such as ste-
roids, azathioprine, and cyclophosphamide [4]. This case report
highlights the consequences of discontinuing dexamethasone-
cyclophosphamide pulse (DCP) therapy and the successful rein-
troduction of treatment, resulting in disease remission.
2 | Case Presentation
A 66- year- old male presented with worsening skin blisters and
erosions over the past 2 months. The patient had a history of
PF, diagnosed 1 year ago. Initially, the patient presented with
multiple blisters and erosions on the skin and was treated with
monthly DCP therapy and oral plus topical steroids. However,
he discontinued the DCP therapy and ceased taking medica-
tions because of affordability issues. Table 1 summarizes the
timeline of events that happened to this patient.
On physical examination (see Figures 1 and 2), the patient
exhibited multiple flaccid bullae and erosions on the face,
scalp, chest, and back, with no mucosal involvement. The
pattern of the disease is very significant and most likely indi-
cates PF [2].
This is a n open access ar ticle under the terms of t he Creative Commons Attr ibution License, which p ermits use, dis tribution and repro duction in any medium, p rovided the orig inal work is
properly cited.
© 2024 T he Author(s). Clinical Ca se Reports publ ished by John Wiley & S ons Ltd.
2 of 5 Clinical Case Reports, 2024
3 | Differential Diagnosis
Differential diagnosis of PV and PF was made according to the
history and examination of the patient.
4 | Investigations
At the time of presentation, his vital signs were as follows: blood
pressure 120/70 mmHg, heart rate 110 bpm, temperature 100°F,
respiratory rate 12/min, and oxygen saturation 97% at room air.
Baseline laboratory tests were performed. The complete blood
count (CBC) revealed hemoglobin of 11.3 g/dL, total leukocyte
count of 10,300/μL, and platelet count of 248,000/μL. Liver
function tests (LFTs) showed bilirubin at 0.4 mg/dL, alanine
transaminase at 34 U/L, and alkaline phosphatase at 240 U/L.
Renal function tests (RFTs) indicated urea at 38 mg/dL and
creatinine at 1.0 mg/dL. Urinalysis (UA) was normal, with no
protein, glucose, or red blood cells detected. Serum electrolytes
showed sodium at 137 mmol/L and potassium at 4.9 mmol/L.
A biopsy was taken from the back of the neck to rule out differ-
entials. Histopathology showed a normal epidermis with focal
hyperkeratosis, an intraepidermal split at the level of the sub-
corneum and granular layer (see Figure3), and a blister cavity
containing numerous acantholytic cells. The epidermis beneath
the blisters showed spongiosis with focal basal layer vacuolation
and dermal edema (see Figure 4) with numerous neutrophils
and lymphocytes in the papillary dermis. These histopathologi-
cal features, along with clinical symptoms, confirmed the diag-
nosis of PF.
5 | Management
The patient had previously discontinued medication because of
cost concerns. Upon reinitiation, the health- care team enrolled
the patient in a medication assistance program, resolving the
cost issue. The patient was started on oral prednisolone 60 mg/
day and oral azathioprine 50 mg/day, along with calcium and
potassium chloride supplementation to address steroid- induced
electrolyte imbalances. Treatment was organized into a phased
schedule to achieve remission and maintain long- term disease
control. Initially, the patient received dexamethasone (100 mg in
500 mL 5% dextrose) over 2 h for three consecutive days, along
with 500 mg of cyclophosphamide on day 1 of each pulse. This
DCP is repeated every 4 weeks [5]. Throughout the treatment,
the dose of prednisolone was gradually tapered at each visit
based on the patient's response and improvement in symptoms.
This approach helped reduce the risks associated with long- term
steroid use while maintaining disease control. The patient was
also advised to apply topical salicylic acid with liquid paraffin to
the lesions and to bathe daily.
6 | Outcome and Follow- Up
Following this treatment, the patient's disease entered re-
mission, characterized by the absence of new lesions and the
healing of existing ones. Regular follow- up visits are sched-
uled every month for continued- DCP therapy and laboratory
monitoring, including CBC, LFT, UA, and RFT, to assess po-
tential side effects from long- term cyclophosphamide and
steroid use. Adjustments to the treatment plan will be made as
necessary.
This regimen will continue for 6 months, after which, if re-
mission is sustained, the monthly pulses will be discontinued
[5]. However, the oral steroid- sparing therapy will continue
for another 9 months [5]. Regular follow- up is crucial to main-
taining long- term disease control, ensuring patient compli-
ance, and preventing relapses in autoimmune conditions such
as PF.
7 | Discussion
PF presents with superficial flaccid bullae that rupture easily,
leading to erosions, pa rticularly in seborrheic area s [2]. Diagnosis
can be made through a skin biopsy, which reveals characteristic
Summary
Adherence to a well- structured immunosuppres-
sive regimen is essential for managing pemphigus
foliaceus.
Noncompliance, often because of affordability, can
worsen symptoms.
The phased approach of dexamethasone-
cyclophosphamide pulse therapy, combined with
prednisolone and azathioprine, improves patient
outcomes.
• Consistent follow- up and patient support are key to
improving adherence and preventing relapse.
TABLE  | Timeline of Events .
Date Event
1 year ago Initial presentation with multiple blisters and erosions.
8 months ago Diagnosed with PF, started on monthly DCP therapy and oral steroids.
6 months ago Discontinued pulse therapy and ceased taking medications.
2 months ago Worsening of blisters and erosions in seborrheic areas.
Current Presented with worsening of symptoms, the patient was reinitiated
on DCP therapy along with steroids and steroid- sparing drugs.
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histopathological features [3, 6]. Immunofluorescence is not
always necessary, as histopathology can differentiate PF
from PV by showing an intraepidermal split at the level of the
subcorneum and granular layer [3]. PF predominantly affects
the stratum corneum, unlike PV, which affects deeper skin lay-
ers near the dermis and involves the oral cavity [7]. PV produces
anti- Dsg1 Ab and Dsg3 Ab, with Dsg3 present in the oral cavity,
leading to oral involvement. In contrast, PF usually produces Ab
only against Dsg1, which is not present in oral mucosa, explain-
ing the lack of mucosal involvement in PF.
This case underscores the importance of adherence to immu-
nosuppres sive therapy in manag ing the condition. The patient's
discontinuation of DCP therapy led to a significant worsen-
ing of symptoms, which were subsequently controlled upon
FIGUR E  | Erosions on chest, neck, and face of the patient.
FIGUR E  | Ruptured f laccid bullae leav ing behind erosions on the
back of the patient.
FIGUR E  | The histopathology slide shows an intraepidermal split
at the level of the subcorneum and granular layer. The deeper dermis
is intact.
FIGUR E  | The slide shows spongiosis with focal basal layer
vacuolation, dermal edema with numerous neutrophils, and
lymphocytes in the papillary dermis.
4 of 5 Clinical Case Reports, 2024
reinitiation of the therapy. The strengths of this case include the
detailed histopathological analysis and clear demonstration of
the clinical improvement with resumed treatment. Literature
suggests that consistent immunosuppressive therapy is crucial
in maintaining remission in PF. Cyclophosphamide is a potent
immunosuppressive agent that has shown efficacy in inducing
and maintaining remission in PF [8]. It works by reducing the
immune system's attack on the skin, thereby preventing the
formation of new blisters and promoting the healing of existing
lesions. The combination of cyclophosphamide with steroids,
such as prednisolone, enhances the therapeutic effect and
helps in faster control of the disease [9]. Azathioprine, added
to the treatment regimen, is an effective and more affordable
steroid- sparing agent. It works by inhibiting DNA synthesis in
rapidly dividing cells, including those of the immune system,
thus reducing the autoimmune response [10, 11]. Rituximab,
a potent anti- B- cell agent, has demonstrated efficacy in PF by
targeting B cells and reducing autoantibody production [2].
The patient's financial limitations precluded the use of ritux-
imab, which has shown superior outcomes in some studies but
is costly [12].
Monitoring disease remission typically involves checking for
new lesion formation. A limitation of this case is the lack of
long- term follow- up data after therapy was reinitiated. Dsg1 Ab
ELISA can be used to monitor disease remission in addition to
clinical evaluation [13, 14]. However, in this patient, only clin-
ical assessment was performed because of the visible healing
of lesions and the absence of new lesions, indicating remission.
It represents a limitation of the report, as Ab titers were not
measured.
8 | Conclusion
This case highlights the importance of immunosuppressive
therapy in managing PF. Discontinuation can lead to severe
symptom exacerbation, whereas reinitiation effectively induces
remission. Patient compliance and access to affordable treat-
ment are crucial for success. A phased regimen of cyclophos-
phamide and prednisolone, with maintenance DCP therapy and
azathioprine as a steroid- sparing agent, proved effective. The
structured, phased approach ensured long- term disease control
and improved patient outcomes.
Author Contributions
Masab Ali: conceptualization, data curation, formal analysis, inves-
tigation, project administration, resources, super vision, validation,
visualization, writing – original draft, writing – review and editing.
Muhammad Husnain Ahmad: visualizat ion . Ali Imran : validation,
visualization, writing – rev iew and editing. Uswa Ahmad: resources,
visualization, writing – rev iew and editing. Rehan Naseer Ahmad:
validation, visualization.
Acknowledgments
We thank the patient for consenting to the publication of this case re-
port. We also acknowledge the health- care team involved in the pa-
tient's care.
Consent
Written informed consent was obtained from the patient to publish this
report in accordance with the journal 's patient consent policy.
Conflicts of Interest
The authors declare no conflicts of interest.
Data Availability Statement
The data is available upon reasonable request from the corresponding
author.
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