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\begin{document}

\title{Rare pyoderma gangrenosum correlated with systemic lupus erythematosus:
A case report}



\author[1]{omid pourbagherian}%
\author[2]{kamran javidi}%
\author[1]{mohammd taghizadieh}%
\author[1]{Mehdi Jafarpour}%
\affil[1]{Tabriz University of Medical Sciences}%
\affil[2]{Tabriz Medical University}%


\vspace{-1em}



  
  \date{March 14, 2025}


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\textbf{Rare pyoderma gangrenosum correlated with systemic lupus
erythematosus: A case report}

Omid pourbagherian\textsuperscript{1}, Kamran Javidi\textsuperscript{1},
Mohammad Taghizadieh\textsuperscript{3}, Mehdi
Jafarpour\textsuperscript{2*}

\textsuperscript{1} Immunology Research Center, Tabriz University of
Medical Sciences, Tabriz, Iran

\textsuperscript{2}Connective Tissue Diseases Research Center, Tabriz
University of Medical Sciences, Tabriz, Iran

\textsuperscript{3}Department of Pathology, Tabriz University of Medical
Sciences, Tabriz, Iran.

Drafting of the manuscript: Mehdi Jafarpour, Omid pourbagherian

Data Collection: Kamran Javidi, Mohammad Taghizadieh, Mehdi Jafarpour

Critical revision of the manuscript for important intellectual content:
Mehdi Jafarpour, Omid pourbagherian

Case supervision: Mehdi Jafarpour

Corresponding author: Mehdi Jafarpour

Address: Connective Tissue Diseases Research Center, Flat 1, Imam Reza
Hospital, Tabriz, Iran

Phone number: 0098 41 33332704

Fax: 0098 41 35413520

Mobile: 09148651269

Reference count: 10

Figure/table count: 2/1

Funding: none.

Conflict of interest: none

Written informed permission from the patient to publish the facts and
photographs was granted.

Manuscript word count:999

\textbf{Keywords}

Pyoderma gangrenosum, Systemic lupus erythematosus, inflammatory skin
disease

\textbf{Introduction}

Pyoderma gangrenosum (PG) is an infrequent kind of inflammatory skin
disease that may lead to the development of swiftly expanding and
distressing skin ulcers(1). The initial documentation of PG was
conducted by Dr. Louis Brocq in 1916. However, it was not until the
1930s that Dr. Brunsting characterized a series of patients with
identical clinical symptoms(2). The etiology of PG remains unclear;
however, it is hypothesized to be an autoimmune condition characterized
by the immune system's attacks on healthy tissue, resulting in the
development of ulcerations.PG impact individuals of all gender, race, or
ages, albeit with a higher incidence rate among adults and a greater
prevalence among the female (3).

PG is correlated with fundamental medical conditions, including
inflammatory bowel disease (IBD), rheumatoid arthritis, lupus, and
specific blood disorders. It is plausible for it to manifest consequent
to pharmaceutical administration or subsequent to surgical intervention
or physical injury(4).The concurrent development of PG with systemic
lupus erythematosus (SLE) is an infrequent phenomenon, with only a
limited number of cases having been documented.

PG can be classified into multiple groups, which include:

1.Classic PG: The prevalent manifestation which is distinguished by the
prompt emergence of distressing ulcers featuring elevated, purple
borders

2.Bullous PG: This form can be identified by the emergence of vesicles
containing fluid that rapidly disintegrates, forming ulcers.

3.Pustular PG: This form can be recognized by the appearance of multiple
small pustules that amalgamate to create distressing ulcers.

4.Vegetative PG: This class stands out by the emergence of skin lesions
resembling cauliflower growths that pose a challenge for effective
management.

5.Postoperative PG: This type manifests after surgical procedures and is
believed to be associated with skin trauma or injury.

6.Systemic PG: The last form is linked with systemic illnesses, such as
rheumatoid arthritis and rarely SLE(5).

The clinical manifestations of PG include the emergence of one or
multiple painful, swiftly advancing ulcers or lesions with uneven
margins and a necrotic core. It is noteworthy that the clinical
manifestation of PG has the potential to resemble other medical
conditions, including infections, malignancies, or autoimmune disorders.
Therefore, an accurate diagnosis necessitates a comprehensive medical
assessment(3).

PG is a condition that can be effectively managed through various
treatment modalities which may encompass corticosteroids,
immunosuppressive medications, antibiotics, and surgical intervention.
Timely medical intervention is crucial in cases of PG, as prompt
treatment can mitigate the risk of complications and enhance prognosis.

\textbf{CASE REPORT}

The subject of this case study is a female patient who is 55 years old
and has been diagnosed with lupus for 20 years. Additionally, she has
been diagnosed with lupus nephritis for 14 years and has been receiving
intermittent treatment with immunosuppressive and corticosteroid
medications such as hydroxychloroquine, cyclosporine, mycophenolate
mofetil, and prednisolone in varying dosages. The aforementioned patient
had severe skin lesions in the form of two painful papules in the
anterior and lateral areas of the leg. These papules progressively
became larger and transformed into an ulcerated lesion with 5\selectlanguage{ngerman}×5 cm
dimensions, and the center of the lesions was found to be necrotic
(Figure 1). Concomitant with the disease, the individual exhibited a
malar rash, small joint arthritis, and renal involvement.

The individual exhibiting these clinical manifestations was admitted to
the Rheumatology Department at Imam Reza Hospital in Tabriz, where,
based on following consultation with the medical team, the patient was
scheduled to undergo a skin biopsy as a means to pursue further
investigation. The dermatology team conducted a skin biopsy (Figure 2).
The biopsy's pathology results showed skin tissue with compact
hyperkeratosis, acanthosis, associated with superficial dermal fibrosis
and intradermal neutrophilic abscess formation, and leukocytoclastic
vasculitis which was compatible with PG, in the early stage.

Initial results of laboratory blood tests revealed elevated levels of
erythrocyte sedimentation rate~(ESR) and C-reactive protein (CRP). Also,
levels of anti-dsDNA antibody increased. The levels of other blood test
parameters are shown in Table 1.

The patient was treated with pulse therapy of methylprednisolone (1g)
for 3 consecutive days and an injection of Cyclophosphamide (750m\selectlanguage{english}fg).
Subsequently, prednisolone dosage began~tapering

gradually (40 mg) and Cyclophosphamide was injected monthly.

.

\textbf{DISCUSSION}

PG is an uncommon kind of inflammatory skin disease that is not caused
by an infection and is characterized by painful necrotic ulcers that
often appear on the legs(6). It is believed that PG is an autoimmune
disease; however, the exact cause of the disease is not completely
known.

Although PG is frequently linked with systemic conditions such as
inflammatory bowel disease, rheumatoid arthritis, and hematologic
malignancies, the incidence of PG as a prior symptom of SLE is very
uncommon and has only been described in a few individuals to this
point(7).

The identification of PG is established through the process of excluding
other potential sources of cutaneous ulcerations that present with
similar characteristics, such as infections, cancers,
vasculitides,~venous insufficiencies, and trauma(8).

To date, in the majority of cases that have been documented, before the
manifestation of PG symptoms, a diagnosis of SLE was made. H. B. Kwon et
al. delineated the clinical manifestation of PG in a female patient aged
35 years, who exhibited the characteristic symptom of painful ulcers on
her lower extremities as our case. The subsequent assessment indicated
that the patient also presented with SLE, posited as the fundamental
etiology of her dermatological manifestation. They deliberate on the
plausible mechanisms that connect the two aforementioned conditions and
underscore the significance of prompt identification and
intervention(9).

In another case study, S. N. Jha et al. demonstrated a female patient,
aged 30 years, diagnosed with SLE, presented with PG affecting her lower
limbs. The authors delve into the plausible immunological mechanisms
that underlie this correlation and emphasize the significance of
interdisciplinary administration(10).

\textbf{Conclusion}

In this case study article, we demonstrated a rare case of PG related to
SLE. The results of our study provide evidence for a potential
correlation between active SLE and PG, although the underlying mechanism
remains unknown. Considering the treatment which our team performed with
a complete recovery, we suggested this first-line treatment strategy.

\textbf{Acknowledgments}

The authors express their gratitude for the valuable contribution made
by the patient in providing biopsy and blood donation.

The authors appreciate support provided by Imam Reza Hospital, Tabriz,
Iran.

\textbf{Author contributions}

All authors approved the final manuscript.

\textbf{Funding}

Not applicable

\textbf{Declarations}

Ethics approval and consent to participate.

This study has been performed according to the Declaration of Helsinki.

\textbf{Competing interests}

The authors declare that they have no competing interests.\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/image1/image1}

\end{center}
\end{figure}

\textbf{Figure 1} . A mucopurulen painful and ulcerated lesion of right
sided foot with irregular borders compatible with pyoderma gangrenosum.\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/image2/image2}

\end{center}
\end{figure}\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/image3/image3}

\end{center}
\end{figure}

\textbf{Figure 2.} A Microscopic view (histologic) of bar-shaped skin
with subcutaneous tissue (H\&E, \selectlanguage{ngerman}×10) showed hyperkeratosis, and
acanthosis, associated with superficial dermal fibrosis and intradermal
neutrophilic abscess formation.

\textbf{Table 1.}

Blood test results of the patients at initial medical examination\selectlanguage{english}
\begin{longtable}[]{@{}lll@{}}
\toprule
Laboratory tests (unit) & Laboratory values & Normal
range\tabularnewline
\midrule
\endhead
WBC (\selectlanguage{ngerman}×1000/\selectlanguage{greek}µ\selectlanguage{english}l) & 8.1 & 4.0-11.0\tabularnewline
Hb (g/dl) & 8 & 12-18\tabularnewline
Plt (\selectlanguage{ngerman}×1000/\selectlanguage{greek}µ\selectlanguage{english}l) & 151 & 130-440\tabularnewline
ESR 1nd hr (mm/hr) & 80/20 & Female: \textless{} 50 Years up to
30\tabularnewline
CRP (mg/L) & 86/6 & Up to 6\tabularnewline
ANA (IU/mL) & Positive & \textless{} 30.0\tabularnewline
Anti dsDNA (IU/mL) & 100/20 & ~\textless{} 10\tabularnewline
C3 mg/dL & 70/90 & ~75 to 175\tabularnewline
C4 mg/dL & Normal & 16 to 48\tabularnewline
Aps Ab U/L & Negative & ~8 to 33\tabularnewline
Creatinine (mg/dl) & 2 & 16-120\tabularnewline
Urea (mg/dl) & 108 & 12.8-43\tabularnewline
LFT & Normal & -\tabularnewline
24 hr urine protein (mg/m\textsuperscript{2}/ day) & 1200 &
\textless{}100\tabularnewline
\bottomrule
\end{longtable}

\textbf{References}

1. Powell FC, Collins S. Pyoderma gangrenosum. Clinics in dermatology.
2000;18(3):283-93.

2. Ye MJ, Ye JM. Pyoderma gangrenosum: a review of clinical features and
outcomes of 23 cases requiring inpatient management. Dermatology
research and practice. 2014;2014:461467.

3. Skopis M, Bag-Ozbek A. Pyoderma gangrenosum: a review of updates in
diagnosis, pathophysiology and management. J. 2021;4(3):367-75.

4. Callen JP. Pyoderma gangrenosum and related disorders. Medical
Clinics of North America. 1989;73(5):1247-61.

5. Bhat RM. Pyoderma gangrenosum: An update. Indian dermatology online
journal. 2012;3(1):7.

6. Braswell SF, Kostopoulos TC, Ortega-Loayza AG. Pathophysiology of
pyoderma gangrenosum (PG): an updated review. Journal of the American
Academy of Dermatology. 2015;73(4):691-8.

7. Brooklyn T, Dunnill G, Probert C. Diagnosis and treatment of pyoderma
gangrenosum. Bmj. 2006;333(7560):181-4.

8. Kozono K, Nakahara T, Kikuchi S, Itoh E, Kido-Nakahara M, Furue M.
Pyoderma gangrenosum with increased levels of serum cytokines. The
Journal of Dermatology. 2015;42(12):1186-8.

9. Kwon HI, Paek JO, Kim JE, Ro YS, Ko JY. Pyoderma gangrenosum in a
patient with hereditary spherocytosis. The International Journal of
Lower Extremity Wounds. 2016;15(1):92-5.

10. Jena A, Sachan A, Singh AK, Sharma V. Multifocal pyoderma
Gangrenosum at presentation in a patient with acute severe ulcerative
colitis. Inflammatory Bowel Diseases. 2022;28(6):e84-e5.

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