Pyoderma Gangrenosum Dermatologic Disorders – A Case Report

Dr. Faisal Aman

MBBS, DDVL

Consultant Dermatologist, Venereologists, Leprologists and Cosmetologist

Bhopal, Madhya Pradesh

Introduction

Pyoderma gangrenosum (PG) is a rare and chronic inflammatory skin disorder that causes the formation of painful ulcers on the skin with hemorrhagic exudates. The ulcers typically begin as small, red, tender bumps that quickly progress to large, deep and necrotic (dead tissue) ulcers. The ulcers are typically accompanied by erythema (redness) and purulence (pus) around the edges. The ulcers can occur anywhere on the body, but are most commonly found on the legs, the lower abdomen and the genitals. Pyoderma gangrenosum is a type of neutrophilic dermatosis, which means that it is characterized by an accumulation of neutrophils (a type of white blood cell) in the affected area of the skin.1

Many variants of pyoderma gangrenosum are observed: Peristomal pyoderma gangrenosum, pustular pyoderma gangrenosum, bullous pyoderma gangrenosum and vegetative pyoderma gangrenosum.2

Some common symptoms associated with pyoderma gangrenosum include:1

• Painful skin ulcers that can be deep and large

• Redness and swelling around the ulcer

• Tenderness or warmth in the affected area

• Pus or drainage from the ulcer

• Fatigue

• Fever

The exact cause of pyoderma gangrenosum is unknown, but it is thought to be a type of immune-mediated disorder. Some cases have been associated with underlying inflammatory conditions such as inflammatory bowel disease, ulcerative colitis rheumatoid arthritis, hematologic disorders and myelodysplastic syndrome.2 It is also reported that pyoderma gangrenosum is an outturn from some drug regimen like propylthiouracil, pegfilgastrim and gefinib. Also in immunocompromised host due to exposure to some bacterial infection.1

The diagnosis of pyoderma gangrenosum is based on clinical presentation and the exclusion of other conditions. It is mainly diagnosed based on the patient's history, physical examination and the appearance of the ulcers. A skin biopsy may be performed to confirm the diagnosis.1 The treatment of pyoderma gangrenosum typically involves a combination of therapies, including topical and systemic immunosuppressive medications, antibiotics, biologics wound care and surgery. The goal of treatment is to control the inflammation and promote healing of the ulcers.3

It is a rare, chronic and a debilitating condition with a potential of affecting the quality of life of the patient. Early diagnosis and appropriate management can help in preventing the formation of deep and extensive ulcers, which can lead to significant scarring and disfigurement.

Clinical Presentation

Pyoderma gangrenosum typically presents as painful ulcers on the skin. The clinical presentation can vary depending on the stage of the condition and the location of the ulcers. The most common presentation of pyoderma gangrenosum is a painful, violaceous and necrotic ulcer that may be preceded by a minor skin injury or infection.4 Mainly it presents ulcers which are deep and defined borders; having undermined edge accompanied by erythromatous or lesions skin encircling the wound.2 Primarily observed on the lower legs especially near the pretibial area.1

Some common features of pyoderma gangrenosum include:

1. Ulceration: The ulcers typically begin as small, red and tender bumps that quickly progress to large, deep and necrotic (dead tissue) ulcers. These ulcers have usually cat paw like appearance.2

2. Erythema: The ulcers are typically accompanied by erythema (redness) and purulence (pus) around the edges with edema.1

3. Tenderness: The ulcers are typically painful and tender to the touch.1

4. Malodorous: Owing to secondary infection, a purulent cover is formed over the ulcers.1

5. Rapid progression: The ulcers can grow rapidly, often within a matter of hours or days.3

6. Pruritus: Itching is a common complaint in patients with pyoderma gangrenosum.

7. Systemic symptoms: Patients may also experience systemic symptoms such as fever, malaise and weight loss.2

8. Hepatitis C, ulcerative colitis, rheumatoid arthritis, lymphoproliferative disorders and myelodysplastic syndrome are believed to be the underlying diseases which can cause pyoderma gangrenosum.1

The clinical presentation of pyoderma gangrenosum can be variable and it may be mistaken for other skin disorders such as cellulitis, necrotizing fasciitis or vasculitis. A biopsy is often performed to confirm the

diagnosis.2

Case Report

A 35 year old male patient was presented to the outpatient department with complaint of painful ulcerations on both lower limbs since past three months. He initially found few boils which on given period of time grew bigger to erythematous ulcers. On further investigation found the person was is non diabetic and non hypertensive and farmer by occupation. He is non smoker and didn't show any presence of varicosity on both limbs. On clinical examinations showed violet or blue coloured ulcers with well defined border, vasculitis on the ridges of ulcers and some areas of thrombosis were observed. Differential diagnosis initially was infective ulceration which was then sent for skin biopsy which revealed deep folliculitis and a network of neutrophilic infiltrate. Which further lead to the conclusion of pyoderma gangrenosum.

Some treatments were then started which included methyl prednisolone (16 mg) tablet to be taken in the morning and night for 5 days, tablet methotrexate 7.5 mg once a week for 2 weeks, folic acid supplement one tab in night for 15 days, Cefprozil 500 mg twice daily for 5 days and hydroxyzine hydrochloride in night for 7 days.

Clinical Examination

Pyoderma gangrenosum is a rare and serious skin condition that typically requires an accurate diagnosis and prompt treatment to prevent serious complications. Early diagnosis is must to avoid any future implications of secondary infections leading to formation of disfiguring scars which many cause difficulties in diagnosis.5 Pyoderma gangrenosum is often diagnosed based on the patient's medical history, physical examination and the characteristic appearance of the affected skin.4 There are no specific laboratory findings for this condition.

However, some confirmatory test undertaken is as follows:

1. Clinical examination: Any diseases if present, progression of ulcers and effectiveness of therapy prescribed.4

2. Physical examination: Ulcers, erythema and involvement of any other internal organs.4

3. Biopsy: A skin biopsy may be performed to confirm the diagnosis. It is sent for detection of histopathology of the existing state along with test for acid fast bacilli.6 The biopsy typically shows a neutrophilic infiltrate in the dermis and subcutaneous tissue.1

4. Pathergy test: A positive pathergy test, which is a skin reaction to a needle prick, is seen in about 40% of cases.6

5. Laboratory tests: Blood tests may be done to rule out underlying conditions that can cause pyoderma gangrenosum such as inflammatory bowel disease, rheumatoid arthritis and myelodysplastic syndrome.2

7. Imaging: Imaging studies like X-rays, CT scans or MRI, abdominal ultrasound, endoscopy and colonoscopy if digestive symptoms are presented these may be done to rule out underlying conditions.4

A definitive diagnosis of pyoderma gangrenosum can be challenging, as it can mimic other skin conditions, such as cellulitis, necrotizing fasciitis or vasculitis. A biopsy is often performed to confirm the diagnosis and exclude other conditions. As biopsy aids in eliminating any other ailments like malignancy, vaculitis or infection.2 Once the diagnosis is made, the treatment plan can be formulated accordingly.

Treatment

Pyoderma gangrenosum is a rare skin condition that typically requires treatment by a dermatologist or other specialist. Main aim of therapy is to reduce tissue destruction and enhance healing of the wound. Through medication relieve from existing ulcers and inhibition from formation of new ulcers should be the primary motive of any medication.2

Treatment options may include: Topical medications to control infection, corticosteroids (topical), immune-suppressing medications, systemic therapy, biologic medications and surgery.3

Topical treatments

Corticosteroids: On initial stages doctors often prescribe oral corticosteroids for remission. Prednisolone being the preferred drug and usually given on high doses. On chronic exposure to these high doses have lead to some steroid related side effects.1 This is an effective treatment in case of unilesional pyoderma. Size of the lesion is an effective parameter in determining time of healing.3

Tacrolimus: It is topical calcineurin inhibitors. The main mechanism involved is reduction in the inflammatory cytokines (IL-2, IL-3 and interferon-y) generations and promotion of lymphocyte proliferation. Usually advised to apply twice a day.3 Sometimes it has said to show systemic absorption.3

Pimecrolimus: It is also a calcineurin inhibitor having primary actions such as reduction in augmentation of T-cell and its further activation process, prevents degranulation and release of further proinflammatory cytokines. It is mainly preferred in conditions like mild localized pyoderma gangrenosum. Sometimes as an adjunct therapy to some systemic drugs in case where conditions are severe or unresponsive.3

Sometimes even topical cyclosporine is used in refractory cases. It has appeared to exempt from tolerability issues which is main problem linked to systemic treatment.3

Systemic therapy

In cases of rapidly proliferative condition use of systemic drug is a must.

Systemic Corticosteroids

It is the first line therapy which is adopted by many doctors. It mainly shows antiinflammatory effects along with down regulation of proinflammatory cytokines and chemokines involved in its pathogenesis.3 They also heckle ulcerative progression and thereby new lesions are prohibited.4 Prednisolone are mostly administered and methylprednisolone for action of pulse therapy.1

Immunosuppressive: Since the main pathophysiology associated is an alteration in immune system, which implies that immune suppressive stands out as one of the treatment. Administered topically or systemically depending on severity of wound.5 Mainly cyclosporine, azathioprine, methotrexate and mycophenolate mofetil to control the underlying autoimmune disorder.3

Cyclosporine being the main line of therapy which disrupts the synthesis of ILs, particularly IL-2 which is associated T-lymphocyte deactivation process.3

Methotrexate which is another immunomodulating drug mainly involved in release of adenosine which further brings down the inflammation and linked immune response. Also brings about nitric oxide uncoupling which decreases susceptibility of T-cells for appotosis.3

Mycophenolate Mofetil: It mainly acts against inosine monophosphate dehydrogenase (in purine salvage pathway) which further decreases guanosine triphosphate which indirectly decreases the lymphocyte proliferation as it lacks purine salvage pathway. It is mainly used as steroid-sparing agent.3

Azathioprine: It brings down the level of circulating monocytes and also inactivates T- cell. Same pathway as mycophenolate mofetil.3

Biologics

Anti-tumour necrosis factor ɑ agents: Infliximab, adalimumab and golimumab which is an monoclonal antibody against tumour necrosis factor a which binds to soluble form and said to induce apoptosis, etanercept which is a recombinant protein that is associated to neutralise the soluble factors are mainly

used agents.2

Interleukin-1ß Inhibitors: In pyoderma gangrenosum cases it has been observed that there is raising levels of Interleukin-1ß. Commonly used agents are anakinra, canakinumab and gevokizumab.3

Surgery

Autologous split-skin grafts are most adopted methods. It is advised to go for surgery in partly remission cases. Sometimes bioengineered skin is also used which are one of the newer developments.1

Wound care

Moist wound management is very crucial since there is presence of heavy exudates in much ulcerative condition. In such cases dressings (silicone, foam) having many different layers are usually recommended. Also use of adsorbents like alginate (haemostatic properties) for bleeding condition, hydrofiber can be applied.3

The treatment plan will depend on the severity of the condition and the patient's response to therapy. Close follow-up with a healthcare provider is crucial to monitor the condition as some cases, the condition may recur even after successful treatment.

Discussion

Pyoderma gangrenosum is a rare, chronic inflammatory skin condition that causes the development of painful, ulcerating sores. Pyoderma gangrenosum is a debilitating condition that can affect the quality of life of patients. Mainly affects 40–60 years of age.

The exact cause of pyoderma gangrenosum is not known, but it is thought to be related to an abnormal immune response. The condition can occur in individuals of any age and can affect both men and women.1 The diagnosis of pyoderma gangrenosum is based on the patient's history, physical examination and the appearance of the ulcers. A skin biopsy may be performed to confirm the diagnosis.4 Due to the rarity of the condition, some healthcare providers may not be familiar with the diagnosis and management of pyoderma gangrenosum, so referral to a specialist in dermatology or wound care may be necessary. The diagnosis is often made by a dermatologist or a wound care specialist, but it can be challenging as it can mimic other skin conditions.

Symptoms of pyoderma gangrenosum typically include the development of one or more painful, red, swollen sores that may be accompanied by itching or burning. These sores can become deep and large; can result in scarring and disfigurement if left untreated. Pyoderma gangrenosum can also cause fever and joint pain in some individuals.1 There is no one definitive treatment for pyoderma gangrenosum and treatment plans are often tailored to the individual.

Treatment options may include the use of immunosuppressive medications, antibiotics, biologics wound care and surgery.1 The mainstay of treatment for pyoderma gangrenosum is the use of systemic corticosteroids, which are effective in controlling the inflammation and promoting healing. In some cases, immunosuppressive agents such as cyclosporine, azathioprine, methotrexate and mycophenolate mofetil may be needed to control the underlying autoimmune disorder.2 Biologic medications such as TNF inhibitors and IL-1 inhibitors can also be effective in treating pyoderma gangrenosum, especially in cases that are refractory to other treatments. In severe cases, surgery to remove the affected skin may be necessary to prevent sepsis and tissue loss.3

Close follow-up with a healthcare provider is crucial to monitor the condition and adjust treatment as necessary. It is important for patients to seek treatment from a board-certified dermatologist or wound care specialist for proper diagnosis, treatment and management. With proper treatment, the prognosis of pyoderma gangrenosum can be managed; however, it is a chronic condition that requires long-term management.

Conclusion

In conclusion, pyoderma gangrenosum is a rare and chronic skin condition characterized by painful, ulcerating sores and can cause significant morbidity and even mortality if not treated appropriately. The condition is characterized by the sudden onset of painful, violaceous and necrotic ulcers that typically develop on the legs. It may be preceded by a minor skin injury or infection. The condition can be difficult to treat and may require a combination of therapies, including corticosteroids, immunosuppressant’s and wound care. The prognosis for individuals with pyoderma gangrenosum can vary and may depend on the severity of the condition and the effectiveness of the treatment. The mainstay of treatment for pyoderma gangrenosum is the use of systemic corticosteroids, which are effective in controlling the inflammation and promoting healing. In some cases, immunosuppressive agents, biologic medications and surgery may be needed to control the underlying autoimmune disorder. Close follow-up with a healthcare provider is crucial to monitor the condition and adjust treatment as necessary. Due to its chronic nature and the difficulty in treating it, pyoderma gangrenosum can have a significant impact on a person's quality of life. Therefore it is advised to consult with a board-certified dermatologist or a specialist in inflammatory skin conditions as early as possible, as pyoderma gangrenosum can progress quickly and lead to severe complications if left untreated.

The management of pyoderma gangrenosum requires a multidisciplinary approach and close collaboration between a dermatologist and other specialists such as rheumatologist or gastroenterologist. Early diagnosis and treatment can help prevent complications and improve outcomes. Research is ongoing to better understand the causes of pyoderma gangrenosum and to develop new treatment options.

References

1. Wollina, U. Pyoderma gangrenosum – a review. Orphanet J Rare Dis 2, 19 (2007). Https://doi. org/10.1186/1750-1172-2-19

2. Brooklyn T, Dunnill G, Probert C. Diagnosis and treatment of pyoderma gangrenosum. BMJ. 2006 Jul 22;333(7560):181-4. Doi: 10.1136/bmj.333.7560.181. PMID: 16858047; PMCID: PMC1513476.

3. Maronese, C.A., Pimentel, M.A., Li, M.M. et al. Pyoderma Gangrenosum: An Updated Literature Review on Established and Emerging Pharmacological Treatments. Am J Clin Dermatol 23, 615–634 (2022). https://doi. org/10.1007/s40257-022-00699-8

4. Konopka, Clóvis Luíz; Padulla, Geórgia Andrade; Ortiz, Michele Purper; Beck, Anderson Kahl; Bitencourt, Mariana Rechia; Dalcin, Diogo Chagas (2013). Pioderma Gangrenoso: um Artigo de Revisão. Jornal Vascular Brasileiro, 12(1), 25–33. doi:10.1590/S167754492013000100006

5. Skopis, M.; Bag-Ozbek, A. Pyoderma Gangrenosum: A Review of Updates in Diagnosis, Pathophysiology and Management. J 2021, 4, 367-375. https://doi. org/10.3390/j4030028

6. Riyaz N, Mary V, Sasidharanpillai

S, Roshin RA, Snigdha O, Latheef EN, Rahima S, Bindu V, Anupama RN, Sureshan DN, Sherjeena PV. Pyoderma gangrenosum: A clinico-epidemiological study. Indian J Dermatol Venereol Leprol 2017;83:33-39