Interstitial Granulomatous Dermatitis

Interstitial granulomatous dermatitis (IGD) is a rare skin condition characterized by the development of non-infectious, inflammatory nodules or plaques within the dermis, the layer of skin located between the epidermis (outermost layer) and the subcutaneous tissue (deepest layer). IGD was first described in 1993 and has since been classified into several subtypes based on their clinical and histopathological features. In this article, we will discuss the different types of IGD and their defining characteristics.

Classical interstitial granulomatous dermatitis: This is the most common subtype of IGD, accounting for about 75% of all cases. It typically presents as multiple, firm, reddish-brown nodules or plaques on the trunk, limbs, and face. The lesions are usually symmetrical and may be accompanied by mild itching. Histologically, classical IGD is characterized by a dense infiltrate of histiocytes (a type of immune cell) and lymphocytes (another type of immune cell) in the dermis, forming granulomas (collections of immune cells). There may also be areas of necrosis (tissue death) and vasculitis (inflammation of blood vessels).
Palisaded neutrophilic and granulomatous dermatitis: This subtype of IGD is characterized by the presence of palisaded neutrophilic granulomatous dermatitis (PNGD) in the dermis. PNGD is a distinct histological finding, characterized by the presence of palisading neutrophils (a type of white blood cell) surrounding areas of degenerated collagen (a protein found in the skin). Clinically, patients with this subtype of IGD may present with erythematous (red) papules (small raised bumps), plaques (large raised patches), or nodules on the trunk, limbs, and face. The lesions may be painful or itchy.
Interstitial granulomatous drug reaction: This subtype of IGD is associated with the use of certain medications, such as antibiotics, anticonvulsants, and nonsteroidal anti-inflammatory drugs (NSAIDs). It typically presents as erythematous, edematous (swollen), or purpuric (purple) patches or plaques on the trunk and extremities, usually within two to four weeks of starting the medication. The lesions may be accompanied by systemic symptoms, such as fever, malaise, and arthralgia (joint pain). Histologically, interstitial granulomatous drug reaction is characterized by a dense infiltrate of lymphocytes and histiocytes in the dermis, forming granulomas.
Interstitial granulomatous dermatitis with arthritis: This subtype of IGD is characterized by the presence of joint symptoms, such as pain, swelling, and stiffness, in addition to skin lesions. The skin lesions are similar to those seen in classical IGD and may be accompanied by erythema (redness), scaling, and crusting. The joint symptoms may affect multiple joints and are usually mild to moderate in severity. Histologically, interstitial granulomatous dermatitis with arthritis is characterized by a dense infiltrate of histiocytes and lymphocytes in the dermis, forming granulomas.
Interstitial granulomatous dermatitis with cutaneous cords: This subtype of IGD is characterized by the presence of linear, fibrotic cords within the dermis, in addition to the typical histological features of IGD. Clinically, patients with this subtype may present with linear, erythematous cords on the trunk or limbs, which may be associated with itching or pain. The cords may be mistaken for scars

Causes

Possible causes of interstitial granulomatous dermatitis:

Connective tissue diseases: IGD can be seen in patients with systemic lupus erythematosus, rheumatoid arthritis, and other connective tissue diseases. In these cases, the condition is thought to be a manifestation of the underlying autoimmune disease.
Infections: Several types of infections have been associated with IGD, including bacterial infections, viral infections, and fungal infections. In some cases, the infection may be the trigger for the development of the condition.
Medications: IGD has been reported in patients taking a variety of medications, including antibiotics, nonsteroidal anti-inflammatory drugs (NSAIDs), and anticonvulsants. The exact mechanism by which these medications may trigger the condition is not well understood.
Neoplasms: IGD has been reported in association with several types of malignancies, including lymphoma and solid tumors. In some cases, the skin lesions may be the first sign of an underlying neoplasm.
Autoimmune disorders: IGD has been reported in association with autoimmune disorders such as autoimmune thyroid disease and autoimmune hepatitis. In these cases, the condition may be a manifestation of the underlying autoimmune process.
Immunodeficiencies: IGD has been reported in patients with primary immunodeficiency disorders, such as common variable immunodeficiency and X-linked agammaglobulinemia. In these cases, the condition may be related to the impaired immune function.
Granulomatous disorders: IGD can be seen in patients with granulomatous disorders such as sarcoidosis and granulomatosis with polyangiitis. In these cases, the skin lesions may be a manifestation of the systemic disease.
Idiopathic: In some cases, no underlying cause for IGD can be identified, and the condition is classified as idiopathic.
Foreign body reaction: IGD has been reported in association with foreign body reactions, in which the skin reacts to implanted foreign materials such as sutures or prosthetic devices.
Trauma: Trauma to the skin, such as a laceration or puncture wound, can sometimes trigger the development of IGD.
Pregnancy: IGD has been reported in pregnant women, although the exact mechanism by which pregnancy may trigger the condition is not well understood.
Allergic reactions: IGD has been reported in association with allergic reactions to medications, insect bites, and other allergens.
Granulomatous vasculitis: IGD has been reported in association with granulomatous vasculitis, a condition in which the blood vessels become inflamed and damaged.
Cryoglobulinemia: IGD has been reported in patients with cryoglobulinemia, a condition in which abnormal proteins in the blood can form deposits in the skin and other organs.
Familial Mediterranean fever: IGD has been reported in patients with familial Mediterranean fever, a genetic disorder characterized by recurrent episodes of fever and inflammation.
Behçet’s disease: IGD has been reported in patients with Behçet’s disease, a rare inflammatory disorder that affects multiple organ systems.
Pyoderma gangrenosum: IGD has been reported in association with pyoderma gangrenosum, a condition in which painful ulcers develop on the skin.
Dermatomyositis: IGD has been reported in patients with dermatomyositis, a rare inflammatory disorder that affects the skin and

Symptoms

Symptoms of Interstitial granulomatous dermatitis:

Skin Lesions: The most common symptom of IGD is the appearance of raised, red nodules or papules on the skin. These lesions are usually firm to the touch and can range in size from a few millimeters to several centimeters in diameter.
Itching: Itching is another common symptom of IGD. The itching can be mild to severe and can occur both before and after the onset of the skin lesions.
Pain: Pain is not a common symptom of IGD, but some people with the condition may experience pain in the affected areas.
Swelling: Swelling around the affected area can occur in some cases of IGD.
Redness: The skin lesions associated with IGD are usually red in color, and the affected areas may also be red and inflamed.
Skin Thickening: In some cases, the skin overlying the IGD lesions may become thickened.
Scarring: Scarring is not a common symptom of IGD, but in some cases, it can occur if the lesions are left untreated.
Crusting: In rare cases, the IGD lesions may become crusted over.
Ulceration: Ulceration, or the breakdown of the skin, can occur in severe cases of IGD.
Hyperpigmentation: Hyperpigmentation, or darkening of the skin, can occur in some cases of IGD.
Hypopigmentation: Hypopigmentation, or lightening of the skin, can occur in some cases of IGD.
Blistering: Blisters may form in some cases of IGD.
Scaling: Scaling, or flaking of the skin, can occur in some cases of IGD.
Erosion: Erosion, or the loss of the outer layer of skin, can occur in some cases of IGD.
Dry Skin: Dry skin is a common symptom of IGD, and it may be related to the itching and scaling associated with the condition.
Nail Changes: Nail changes, including thickening and ridging of the nails, can occur in some cases of IGD.
Hair Loss: Hair loss in the affected area can occur in some cases of IGD.
Eye Involvement: In rare cases, IGD can affect the eyes, leading to conjunctivitis, iritis, or other eye problems.
Joint Pain: Joint pain and swelling can occur in some cases of IGD, particularly if the condition is associated with an underlying autoimmune disorder.
Systemic Symptoms: Systemic symptoms, including fever, fatigue, and weight loss, can occur in some cases of IGD, particularly if the condition is associated with an underlying autoimmune disorder.

Diagnosis

Diagnosis and tests used to diagnose IGD in detail.

Clinical examination: The initial step in diagnosing IGD is a comprehensive clinical examination, which includes a detailed medical history and physical examination. IGD typically presents as erythematous papules, nodules, or plaques that are often symmetrically distributed on the trunk, extremities, and face. These lesions may be pruritic, painful, or asymptomatic. IGD can also present with other associated symptoms such as fever, malaise, and arthralgia.
Skin biopsy: A skin biopsy is necessary to confirm the diagnosis of IGD. The biopsy specimen should be taken from an active lesion and should include both the dermis and epidermis. Histological examination of the biopsy specimen typically reveals a dense infiltrate of histiocytes, lymphocytes, and multinucleated giant cells in the dermis. There may also be areas of necrosis and fibrosis.
Direct immunofluorescence (DIF) testing: DIF testing is performed on a skin biopsy specimen to identify the presence of immune complexes in the skin. DIF testing may reveal the deposition of immunoglobulin (Ig) G, IgA, IgM, and/or complement component C3 in the dermal vessels and/or interstitium.
Laboratory tests: A complete blood count, erythrocyte sedimentation rate, and C-reactive protein level should be obtained to evaluate for the presence of an underlying systemic disease or infection that may be associated with IGD.
Serological testing: Serological testing may be useful in evaluating for underlying autoimmune or infectious diseases that may be associated with IGD. Testing for antinuclear antibodies (ANA), rheumatoid factor (RF), anti-cyclic citrullinated peptide (anti-CCP) antibodies, and infectious serologies (e.g., hepatitis B and C, HIV, syphilis) may be considered.
Imaging studies: Imaging studies such as chest x-ray, computed tomography (CT), or magnetic resonance imaging (MRI) may be indicated to evaluate for the presence of underlying systemic disease or to assess the extent of skin involvement.
Patch testing: Patch testing is used to identify potential allergens that may be triggering an allergic reaction in the skin. Patch testing involves applying small amounts of various substances to the skin and observing for a reaction. Patch testing is not specific for IGD but may be useful in identifying triggers for a hypersensitivity reaction.
Skin prick testing: Skin prick testing involves pricking the skin with small amounts of allergens to evaluate for a hypersensitivity reaction. Skin prick testing may be useful in identifying potential allergens that may be triggering an allergic reaction in the skin.
Polymerase chain reaction (PCR) testing: PCR testing may be used to identify the presence of infectious agents (e.g., bacteria, viruses, fungi) in skin biopsy specimens. PCR testing may be useful in identifying underlying infectious diseases that may be associated with IGD.
Histopathology: Histopathological examination of skin biopsy specimens is necessary to confirm the diagnosis of IGD. Histological examination typically reveals a dense infiltrate of histiocytes, lymphocytes, and multinucleated giant cells in the dermis. There may also be areas of necrosis

Treatment

Treatments for interstitial granulomatous dermatitis and their effectiveness.

Systemic corticosteroids: Systemic corticosteroids are often used as the first-line treatment for IGD. They are effective at reducing inflammation and can lead to rapid improvement in skin lesions. However, long-term use of corticosteroids can lead to significant side effects, including osteoporosis, diabetes, and immunosuppression.
Topical corticosteroids: Topical corticosteroids are less potent than systemic corticosteroids, but can be effective in treating mild cases of IGD. They are often used in combination with systemic corticosteroids or other treatments.
Methotrexate: Methotrexate is an immunosuppressive agent that is often used in the treatment of autoimmune disorders. It can be effective in treating IGD, but can also cause significant side effects, including liver toxicity and bone marrow suppression.
Azathioprine: Azathioprine is another immunosuppressive agent that is often used in the treatment of autoimmune disorders. It can be effective in treating IGD, but can also cause significant side effects, including liver toxicity and bone marrow suppression.
Cyclosporine: Cyclosporine is an immunosuppressive agent that is often used in the treatment of organ transplant rejection. It can be effective in treating IGD, but can also cause significant side effects, including renal toxicity and hypertension.
Mycophenolate mofetil: Mycophenolate mofetil is an immunosuppressive agent that is often used in the treatment of autoimmune disorders. It can be effective in treating IGD, but can also cause significant side effects, including gastrointestinal disturbances and bone marrow suppression.
Dapsone: Dapsone is an antibacterial agent that is often used in the treatment of leprosy. It can also be effective in treating IGD, but can cause significant side effects, including methemoglobinemia and hemolytic anemia.
Colchicine: Colchicine is an anti-inflammatory agent that is often used in the treatment of gout. It can also be effective in treating IGD, but can cause significant side effects, including gastrointestinal disturbances and bone marrow suppression.
Thalidomide: Thalidomide is an immunomodulatory agent that is often used in the treatment of multiple myeloma. It can also be effective in treating IGD, but can cause significant side effects, including peripheral neuropathy and birth defects.
Chloroquine: Chloroquine is an anti-malarial agent that can also be effective in treating IGD. However, it can cause significant side effects, including retinal toxicity and gastrointestinal disturbances.
Hydroxychloroquine: Hydroxychloroquine is a less toxic version of chloroquine that can also be effective in treating IGD. It can cause gastrointestinal disturbances and skin rashes.
Sulfasalazine: Sulfasalazine is an anti-inflammatory agent that is often used in the treatment of inflammatory bowel disease. It can also be effective in treating IGD, but can cause significant side effects, including gastrointestinal disturbances and bone marrow suppression.

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