Kimura's disease is a benign rare
chronic inflammatory disorder. Its primary symptoms are
subdermal
The subcutaneous tissue (), also called the hypodermis, hypoderm (), subcutis, superficial fascia, is the lowermost layer of the integumentary system in vertebrates. The types of cells found in the layer are fibroblasts, adipose cells, and macro ...
lesions
A lesion is any damage or abnormal change in the tissue of an organism, usually caused by disease or trauma. ''Lesion'' is derived from the Latin "injury". Lesions may occur in plants as well as animals.
Types
There is no designated classif ...
in the head or neck or painless unilateral inflammation of
cervical lymph nodes
Cervical lymph nodes are lymph nodes found in the neck. Of the 800 lymph nodes in the human body, 300 are in the neck. Cervical lymph nodes are subject to a number of different pathological conditions including tumours, infection and inflammati ...
.
Cause
Its cause remains unknown. Reasons such as an allergic reaction, tetanus toxoid vaccination,
or an alteration of immune regulation are suspected. Other theories like persistent antigenic stimulation following arthropod bites and parasitic or candidal infection have also been proposed. To date, none of these theories has been substantiated.
Pathophysiology
The pathophysiology of Kimura's disease remains unknown, although an allergic reaction, trauma, and an autoimmune process have all been implicated as possible causes. The disease is manifested by an abnormal proliferation of lymphoid follicles and vascular endothelium. Peripheral
eosinophilia
Eosinophilia is a condition in which the eosinophil count in the peripheral blood exceeds . Hypereosinophilia is an elevation in an individual's circulating blood eosinophil count above 1.5 x 109/ L (i.e. 1,500/ μL). The hypereosinophilic synd ...
and the presence of
eosinophils
Eosinophils, sometimes called eosinophiles or, less commonly, acidophils, are a variety of white blood cells (WBCs) and one of the immune system components responsible for combating multicellular parasites and certain infections in vertebrates. A ...
in the inflammatory
infiltrate suggest it may be a hypersensitivity reaction. Some evidence has indicated TH2 lymphocytes may also play a role, but further investigation is needed.
Kimura's disease is generally limited to the skin, lymph nodes, and salivary glands, but patients with Kimura's disease and
nephrotic syndrome
Nephrotic syndrome is a collection of symptoms due to kidney damage. This includes protein in the urine, low blood albumin levels, high blood lipids, and significant swelling. Other symptoms may include weight gain, feeling tired, and foamy ...
have been reported. The basis of this possible association is unclear.
= Presentation =
Kimura's disease presents predominantly as subcutaneous nodules in the head and neck, often unilateral, and frequently associated with regional lymphadenopathy with or without the involvement of salivary glands. Sometimes bilateral involvement is also seen. Peripheral blood eosinophilia and elevated serum immunoglobulin E (IgE) levels are constant features of Kimura’s disease. Rarely, it has also been found to affect the skeletal muscle, prostate, kidney, peripheral nerves, eyelid, conjunctiva, eyelid, tympanic membrane, oral cavity, and epiglottis.
Diagnosis
An
open biopsy
An open biopsy is a procedure in which a surgical incision (cut) is made through the skin to expose and remove tissues. The biopsy tissue is examined under a microscope by a pathologist. An open biopsy may be done in the doctor's office or hos ...
is the chief means by which this disease is diagnosed.
"Lymphoid nodules with discrete germinal centers can occupy an area extending from the reticular dermis to the fascia and muscle. Follicular hyperplasia, marked eosinophilic infiltrate and eosinophilic abscesses, and the proliferation of postcapillary venules are characteristic histological findings.
8Centrally, thick-walled vessels are present with hobnail endothelial cells. Immunohistochemical evaluation of the lymphoid nodules demonstrates a polymorphous infiltrate without clonality.
2, 27Reports have also demonstrated the presence of plasmacytoid dendritic cells in a lesion of Kimura disease.
0Histopathological examination is an effective way to establish the diagnosis."
Treatment
Observation is acceptable if the lesions are neither symptomatic nor disfiguring. Intralesional or oral steroids can shrink the nodules, but seldom result in cure. Cyclosporine has been reported to induce remission in patients with Kimura's disease, but recurrence of the lesions has been observed once this therapy is stopped.
Cetirizine is an effective agent in treating its symptoms. Cetirizine's properties of being effective both in the treatment of
pruritus
Itch (also known as pruritus) is a sensation that causes the desire or reflex to scratch. Itch has resisted many attempts to be classified as any one type of sensory experience. Itch has many similarities to pain, and while both are unpleasant ...
(itching) and as an anti-inflammatory agent make it suitable for the treatment of the pruritus associated with these lesions.
[
] In a 2005 study, the American College of Rheumatology conducted treatments initially using
prednisone
Prednisone is a glucocorticoid medication mostly used to suppress the immune system and decrease inflammation in conditions such as asthma, COPD, and rheumatologic diseases. It is also used to treat high blood calcium due to cancer and adren ...
, followed by steroid dosages and
azathioprine
Azathioprine (AZA), sold under the brand name Imuran, among others, is an immunosuppressive medication. It is used in rheumatoid arthritis, granulomatosis with polyangiitis, Crohn's disease, ulcerative colitis, and systemic lupus erythematosus, ...
,
omeprazole, and
calcium
Calcium is a chemical element with the symbol Ca and atomic number 20. As an alkaline earth metal, calcium is a reactive metal that forms a dark oxide-nitride layer when exposed to air. Its physical and chemical properties are most similar t ...
and
vitamin D
Vitamin D is a group of fat-soluble secosteroids responsible for increasing intestinal absorption of calcium, magnesium, and phosphate, and many other biological effects. In humans, the most important compounds in this group are vitamin D3 ...
supplements over the course of two years.
The skin condition of the patient began to improve and the skin lesions lessened. However, symptoms of
cushingoid and
hirsutism
Hirsutism is excessive body hair on parts of the body where hair is normally absent or minimal. The word is from early 17th century: from Latin ''hirsutus'' meaning "hairy". It usually refers to a "male" pattern of hair growth in a female that ...
were observed before the patient was removed from the courses of steroids and placed on 10 mg/day of cetirizine to prevent skin lesions;
an agent suitable for the treatment of pruritus associated with such lesions.
Asymptomatically, the patient's skin lesions disappeared after treatment with cetirizine, blood
eosinophil
Eosinophils, sometimes called eosinophiles or, less commonly, acidophils, are a variety of white blood cells (WBCs) and one of the immune system components responsible for combating multicellular parasites and certain infections in vertebrates. ...
counts became normal,
corticosteroid effects were resolved,
and a remission began within a period of two months.
The inhibition of eosinophils may be the key to treatment of Kimura's disease due to the role of eosinophils, rather than other cells with regards to the lesions of the skin.
Radiotherapy has been used to treat recurrent or persistent lesions. However, considering the benign nature of this disease, radiation should be considered only in cases of recurrent, disfiguring lesions.
Surgery has been considered the mainstay of therapy. However, recurrence after surgery is common.
In 2011, an eight-year-old boy had presented with a firm, nontender, nonfluctuating 15- to 12-cm mass on the left side of the neck involving the lateral region of the neck and jaw and a 5- to 7-cm mass on the right side of his neck. He had an eosinophil concentration of 36% (absolute count: 8172/mL), his
IgE level was 9187 IU/mL. He was diagnosed with Kimura's disease. Initially treated with corticosteroids, he was given a single dose of
intravenous immunoglobulin (IVIG) as a steroid-sparing agent after the disease flared while tapering
prednisone
Prednisone is a glucocorticoid medication mostly used to suppress the immune system and decrease inflammation in conditions such as asthma, COPD, and rheumatologic diseases. It is also used to treat high blood calcium due to cancer and adren ...
. After IVIG administration, improvement was rapid, both left and right cervical masses diminished to less than 1 cm and his eosinophil and IgE levels returned to normal range. He has been free of disease during a six-year follow-up. IVIG may have value in the treatment of Kimura's disease.
A study is going on to assess the efficacy of tacrolimus on Kimura's disease. One case has so far been described. A patient with refractory Kimura's disease after surgery and treatment with prednisone was treated with tacrolimus.
Tacrolimus
Tacrolimus, sold under the brand name Prograf among others, is an immunosuppressive drug. After allogeneic organ transplant, the risk of organ rejection is moderate. To lower the risk of organ rejection, tacrolimus is given. The drug can als ...
(FK-506) was administered at an initial dosage of 1 mg every 12 hours, and FK-506 concentration in the blood was monitored monthly. FK-506 blood concentration was controlled within 5 to 15 μg/L. After 6 months, the dosage of tacrolimus was reduced to 0.5 mg daily for another 2 months and then treatment was stopped. Swelling of the bilateral salivary glands disappeared within the first week. No serious side effects were noted and the disease has not recurred in the 2 years of follow-up. Tacrolimus may be an effective treatment for patients with Kimura's disease, but more research is needed to determine its long-term efficacy and safety, as well as its mechanism of action.
Prevalence
Kimura's disease is said to be predominantly seen in males of Asian descent.
However, a study of 21 cases in the United States showed no racial preference, of 18 males and three females (male/female ratio 6:1), 8 to 64 years of age (mean, 32 years), and seven Caucasians, six Blacks, six Asians, one Hispanic, and an Arab were included.
Assessing the prevalence is difficult. The medical literature alone holds over 500 case reports and series (typically two, three cases) from the 1980s to early 2017 in English, excluding the existing Chinese, Japanese, and Korean medical reports that add more cases.
History
The first known report of Kimura's disease was from
China in 1937, when Kimm and Szeto identified seven cases of the condition.
It first received its name in 1948 when Kimura and others noted a change in the surrounding blood vessels and referred to it as "unusual granulation combined with hyperplastic changes in lymphoid tissue."
See also
*
Kikuchi's disease
*
List of cutaneous conditions
Many skin conditions affect the human integumentary system—the organ system covering the entire surface of the body and composed of skin, hair, nails, and related muscle and glands. The major function of this system is as a barrier agai ...
References
External links
{{Neutrophilic and eosinophilic dermatosis
Eosinophilic cutaneous conditions
Rare diseases
Immune system disorders