Facial lesions are very common and the differential is broad. I will attempt to narrow down the possibilities based on size, appearance and presence or absence of pain.
Pain is a significant symptom, and clustering of the lesions is important as well.
Benign facial growths (such as warts, seborrheic keratoses, moles, basal cell carcinomas, cherry angiomas, dermatofibromas, etc., are not fluid-filled, nor painful, so need not be discussed.
Pre-malignant or malignant skin lesions are also solid, not fluid filled or usually painful.
Bacterial skin infections (acne, abscesses, etc.) are inflammatory, and present as painful, tender areas of swelling and commonly redness, but do not present as clear fluid-filled lesions. Pus may be present with a bacterial skin infection, but pus is white or off white, sometimes blood tinged, not clear. The exception is discussed below.
This leaves blister-like lesions of the face. What are possible causes of blisters on the face? Emphasis will be on the face and small blisters or grouped vesicles. There is a difference between a blister (usually larger than .5 cm) and a vesicle (.1-.4 cm). Also, vesicles can occur singly or in clusters in the same lesion. A cluster of vesicles in the same area may appear to be a blister. They are different.
Varicella Zoster Virus
Before vaccinations became available, the most common cause of blisters on the face was chicken pox. Almost 100% of an unvaccinated population contracts this virus (Varicella Zoster Virus or VZV) at some point in life. While chicken pox is still quite common in many parts of the world, the incidence has fallen considerably in countries routinely vaccinating their young.
The lesions of chicken pox are probably familiar to most adults: multiple small (less than .5 cm) scattered red papules (small bumps on the skin), clear vesicles on a red base, or small crusted lesions on a red base (initially just the papules, followed by lesions in each stage) scattered all over the body. These lesions are very itchy.
Since VZV infects spinal nerves and lies dormant in the body after chicken pox infection, reactivation (called shingles or herpes zoster) is possible. Like chicken pox, the lesions are clear fluid filled small blisters (called vesicles) on a red base. Unlike chicken pox, reactivation most commonly occurs only in one nerve root at a time, on one side of the body, in the skin which that nerve serves, called a dermatome. Also, the lesions tend to be painful (sometimes very much so), and the skin can be exquisitely sensitive.
The trunk of the body is the most common area to be affected, but the face is commonly affected as well.
The clear fluid from a ruptured vesicle contains live viruses, therefore attention should be directed to avoid infecting others.
Contact or Allergic Dermatitis
Contact with certain chemicals can cause blistering of the skin. Industrial strength cleaners, harsh alkaline substances, etc. can cause painful blistering and redness that looks like a second degree burn of the skin. The source of such chemical burns is usually obvious, as the substance irritates the skin on or very closely after contact. The lesions are usually painful and feel like burns. Treatment is similar to that of burns.
A common allergen causing blistering is urushiol, the active organic compound that in poison ivy that causes a form of contact dermatitis. With sufficient contact, an itchy, red, vesicular rash will appear after several days where contact has occurred, accompanied by itching. The lesions caused by poison ivy often tend to be linear (caused by rubbing along the edge of the leaf) or diffuse (on the hands) if one has been handling poison ivy. If handling the plant, and accidentally touching the face or other body part, urushiol can be transferred to the face as well. The diagnosis is made by the appearance, the distribution of the rash, the characteristic itchiness without pain, and the history of outdoor potential exposure.
Impetigo is a skin infection most commonly involving young children, but it is highly infectious, adult close contacts may be affected. There are two types. Nonbullous impetigo starts as as painless or possibly itchy single papule that progresses to a vesicle. The vesicle ruptures, and the lesion secretes clear fluid that forms the typical honey-colored crust. As the fluid is infectious, the lesion grows in diameter, and new lesions appear near to the initial one. It is commonly found near the nose or mouth, but can occur anywhere on the face/exposed areas of the body.
Bullous impetigo forms small to large, soft blisters which break easily. It is not particularly painful although it can resemble a superficial second-degree burn. Bullous impetigo is not common on the face, rather it seems to occur more commonly in moist areas, such as the diaper area (in infants), the underarms, and neck folds.
Herpes Simplex Virus
Once infected with Herpes Simplex Virus (HSV), the virus, like VZV, lives in sensory nerve ganglia. There are two types of HSV, Types 1 and 2. HSV-1 is the common cause of cold sores or "fever blisters", but in fact can infect and recur on any part of the body. HSV-2 is the most common cause of genital herpes. Both viruses are spread by direct contact, so any skin/mucosal membranes directly exposed to either HSV-1 or HSV-2 can become infected, with recurrences common. HSV-1 infection, though it is with the same virus, can have different names depending on the area infected: Herpes labialis (lips), sacral herpes (on back near buttocks), herpetic whitlow (fingers), Herpes gladiatorum (aka 'mat herpes', initially diagnosed in wrestlers with close skin-to-skin contact), etc. Herpes Simplex Virus infections can occur anywhere on the body.
HSV, since it infects sensory nerves, is characterized by a period of pain or tingling preceding and accompanying the outbreak of clustered small vesicles - often more than one cluster - on a swollen, sometimes red base. The first outbreak is usually the most dramatic, but it may be minor and overlooked. The pain can often seem disproportionate to the size of the lesion(s).
Caution should be taken not to spread infectious fluid from ruptured vesicles to the eyes (especially, as it can lead to blindness), to other parts of the body, or to other individuals.
Fixed Drug Eruption
The term fixed drug eruption describes the development of one or more annular or oval erythematous [red] patches as a result of systemic exposure to a drug; these reactions normally resolve with hyperpigmentation [skin darkening] and may recur at the same site with re-exposure to the drug.
Fixed drug eruptions can occur anywhere (including eyes, mouth, tongue, genitals, etc.), and can take many forms. One form may be a blister. This is called a Bullous fixed drug eruption. Symptoms may include itching, burning, and/or pain. There usually isn't pain preceding the eruption.
Initially, a single lesion or a few lesions develop, but, with re-exposure, additional lesions occur. The vast majority of patients present with 1-30 lesions, ranging in size of 0.5-5 cm, but reports of lesions greater than 10 cm have been published. Lesions may be generalized. The most common reported site is the lips, and these may be seen in up to half of all cases.
The initial lesion can be a vesicle or small blister. The characteristic recurrence after one particular drug or class of drugs, hyperpigmentation (more common in dark-skinned individuals), and lack of pain or tingling preceding eruption helps differentiate this from other causes.